PAPERS

Feb
03
Association between mid-upper arm circumference and cardiometabolic risk in Chinese population: a cross-sectional study.
Abstract
OBJECTIVES Upper body fat has been associated with an unfavourable cardiometabolic risk. We aimed to investigate the associations between mid-upper arm circumference (MUAC), a novel indicator of upper body fat, and a wide spectrum of cardiometabolic risk profiles in Chinese population. DESIGN AND SETTING Cross-sectional analyses were performed using data from a well-defined community in 2014, Shanghai, China. PARTICIPANTS A total of 6287 Chinese adults (2310 men and 3977 women) aged 40 years or older. OUTCOME MEASURES Multivariable logistic regression model was used to examine the associations of MUAC with cardiometabolic disorders including central obesity, diabetes, hypertension, hypertriglyceridaemia, low high-density lipoprotein (HDL) cholesterol and subclinical atherosclerosis. RESULTS In the overall participants, after multivariable adjustment, each 1 SD (3.13 cm) increment in MUAC was positively associated with central obesity (OR 2.05; 95% CI 1.85 to 2.28), hypertension (OR 1.10; 95% CI 1.03 to 1.19) and low HDL cholesterol (OR 1.10; 95% CI 1.01 to 1.22). Multivariable-adjusted ORs for subclinical atherosclerosis were gradually increased across increasing quartiles of MUAC with the lowest quartile as reference (quartile 2: OR 1.31; 95% CI 1.09 to 1.58; quartile 3: OR 1.33; 95% CI 1.10 to 1.62; quartile 4: OR 1.45; 95% CI 1.16 to 1.80; p for trend=0.005). Similar but more prominent associations were observed among women than men. In addition, MUAC was significantly interacted with diabetes (p for interaction=0.04) and insulin resistance (p for interaction=0.01) on subclinical atherosclerosis. CONCLUSION A greater MUAC was positively associated with higher risks of several cardiometabolic disorders and subclinical atherosclerosis in Chinese adults.
Yanan Hou, Xu Jia, Liping Xuan, Wen Zhu, Chanjuan Deng, Long Wang, Zhiyun Zhao, Mian Li, Jieli Lu, Yu Xu, Yuhong Chen, Weiqing Wang, Yufang Bi, Min Xu, Tiange Wang,
Causes and Prevention, Prevalence
Cardiovascular
Jan
14
Cardiovascular Risk and Risk Factor Management in Type 2 Diabetes: A Population-Based Cohort Study Assessing Sex Disparities.
Abstract
BACKGROUND With recent changes in UK clinical practice for diabetes care, contemporary estimates of sex disparities in cardiovascular risk and risk factor management are needed. METHODS In this retrospective cohort study, using the Clinical Practice Research Datalink linked to hospital and death records for people in England, we identified 79,985 patients with incident T2DM between 2006-2013 matched to 386,547 patients without diabetes. Sex-stratified Cox models were used to assess cardiovascular risk. RESULTS Compared to women without T2DM, women with T2DM had a higher cardiovascular event risk (adjusted HR 1.20 [95% CI 1.12-1.28]) with similar corresponding data in men (HR 1.12 [1.06-1.19]) leading to a non-significant higher relative risk in women (risk ratio 1.07 [0.98-1.17]). However, some important sex differences in the management of risk factors were observed. Compared to men with T2DM, women with T2DM were more likely to be obese, hypertensive and have hypercholesterolaemia but were less likely to be prescribed lipid-lowering medication and ACE inhibitors, especially if they had CVD. CONCLUSIONS Compared to men developing T2DM, women with T2DM do not have a significantly higher relative increase in cardiovascular risk, but ongoing sex disparities in prescribing should prompt heightened efforts to improve the standard and equity of diabetes care in women and men.
Alison K Wright, Evangelos Kontopantelis, Richard Emsley, Iain Edward Buchan, Mamas A Mamas, Naveed Sattar, Darren M Ashcroft, Martin K Rutter,
Prevalence
Cardiovascular, Diabetes
Jan
06
Medium and long-term risks of specific cardiovascular diseases in survivors of 20 adult cancers: a population-based cohort study using multiple linked UK electronic health records databases.
Abstract
BACKGROUND The past few decades have seen substantial improvements in cancer survival, but concerns exist about long-term cardiovascular disease risk in survivors. Evidence is scarce on the risks of specific cardiovascular diseases in survivors of a wide range of cancers to inform prevention and management. In this study, we used large-scale electronic health records data from multiple linked UK databases to address these evidence gaps. METHODS For this population-based cohort study, we used linked primary care, hospital, and cancer registry data from the UK Clinical Practice Research Datalink to identify cohorts of survivors of the 20 most common cancers who were 18 years or older and alive 12 months after diagnosis and controls without history of cancer, matched for age, sex, and general practice. We compared risks for a range of cardiovascular disease outcomes using crude and adjusted Cox models. We fitted interactions to investigate effect modification, and flexible parametric survival models to estimate absolute excess risks over time. FINDINGS Between Jan 1, 1990, and Dec 31, 2015, 126 120 individuals with a diagnosis of a cancer of interest still being followed up at least 1 year later were identified and matched to 630 144 controls. After exclusions, 108 215 cancer survivors and 523 541 controls were included in the main analyses. Venous thromboembolism risk was elevated in survivors of 18 of 20 site-specific cancers compared with that of controls; adjusted hazard ratios (HRs) ranged from 1·72 (95% CI 1·57-1·89) in patients after prostate cancer to 9·72 (5·50-17·18) after pancreatic cancer. HRs decreased over time, but remained elevated more than 5 years after diagnosis. We observed increased risks of heart failure or cardiomyopathy in patients after ten of 20 cancers, including haematological (adjusted HR 1·94, 1·66-2·25, with non-Hodgkin lymphoma; 1·77, 1·50-2·09, with leukaemia; and 3·29, 2·59-4·18, with multiple myeloma), oesophageal (1·96, 1·46-2·64), lung (1·82, 1·52-2·17) kidney (1·73, 1·38-2·17) and ovarian (1·59, 1·19-2·12). Elevated risks of arrhythmia, pericarditis, coronary artery disease, stroke, and valvular heart disease were also observed for multiple cancers, including haematological malignancies. HRs for heart failure or cardiomyopathy and venous thromboembolism were greater in patients without previous cardiovascular disease and in younger patients. However, absolute excess risks were generally greater with increasing age. Increased risks of these outcomes seemed most pronounced in patients who had received chemotherapy. INTERPRETATION Survivors of most site-specific cancers had increased medium-term to long-term risk for one or more cardiovascular diseases compared with that for the general population, with substantial variations between cancer sites. FUNDING Wellcome Trust and Royal Society.
Helen Strongman, Sarah Gadd, Anthony Matthews, Kathryn E Mansfield, Susannah Stanway, Alexander R Lyon, Isabel Dos-Santos-Silva, Liam Smeeth, Krishnan Bhaskaran,
Diagnosis; Prognosis
Cardiovascular
Dec
10
Inflammatory Bowel Disease Increases Risk of Type 2 Diabetes in a Nationwide Cohort Study.
Abstract
BACKGROUND & AIMS The intestine regulates glucose homeostasis, but it is not clear whether chronic intestinal inflammation affects risk for type 2 diabetes. We investigated the long-term risk of type 2 diabetes in patients with inflammatory bowel diseases (IBD) in a nationwide cohort study in Denmark. METHODS In a nationwide population-based cohort of 6,028,844 persons in Denmark, we compared data from individuals with a diagnosis of IBD (Crohn's disease [CD] or ulcerative colitis UC]) with data from individuals without IBD from 1977 through 2014. Persons with type 2 diabetes were identified in the National Patient Register. Risk is presented as standardized incidence ratios (SIR) with 95% CIs. RESULTS During 736,072 person-years of follow-up, 3436 patients with IBD developed type 2 diabetes vs 2224 expected (SIR, 1.54; 95% CI, 1.49-1.60). The risk was significantly increased in patients with UC (SIR, 1.54; 95% CI, 1.48-1.60), in patients with CD (SIR, 1.57; 95% CI, 1.47-1.67), in women (SIR, 1.51; 95% CI, 1.44-1.59), and in men (SIR, 1.57; 95% CI, 1.50-1.65). The risk was highest the first year after a diagnosis of IBD (SIR, 4.48; 95% CI, 4.16-4.83), but remained increased for 20 or more years following the diagnosis (SIR, 1.26; 95% CI, 1.16-1.38). The increased risk could not be accounted for by frequency of health care contacts or corticosteroid exposure. Patients who received a diagnosis of IBD from 2003 through 2014 (SIR, 1.79; 95% CI, 1.67-1.91) had a significantly higher risk of type 2 diabetes than patients who received a diagnosis of IBD from 1977 through 1988 (SIR, 1.47; 95% CI, 1.39-1.56) or 1989 through 2002 (SIR, 1.48; 95% CI, 1.41-1.56) (P < .001). CONCLUSIONS In a population-based cohort study, we found an increased risk of type 2 diabetes in patients with UC or CD, with highest risk estimates from 2003 through 2014, compared with earlier years. Studies are needed to determine the effects of IBD treatment on risk of type 2 diabetes.
Tine Jess, Britt W Jensen, Mikael Andersson, Marie Villumsen, Kristine H Allin,
Causes and Prevention
Diabetes
Nov
25
High maternal early-pregnancy blood glucose levels are associated with altered fetal growth and increased risk of adverse birth outcomes.
Abstract
AIMS/HYPOTHESIS The study aimed to assess the associations of maternal early-pregnancy blood glucose levels with fetal growth throughout pregnancy and the risks of adverse birth outcomes. METHODS In a population-based prospective cohort study among 6116 pregnant women, maternal non-fasting glucose levels were measured in blood plasma at a median 13.2 weeks of gestation (95% range 9.6-17.6). We measured fetal growth by ultrasound in each pregnancy period. We obtained information about birth outcomes from medical records and maternal sociodemographic and lifestyle factors from questionnaires. RESULTS Higher maternal early-pregnancy non-fasting glucose levels were associated with altered fetal growth patterns, characterised by decreased fetal growth rates in mid-pregnancy and increased fetal growth rates from late pregnancy onwards, resulting in an increased length and weight at birth (p ≤0.05 for all). A weaker association of maternal early-pregnancy non-fasting glucose levels with fetal head circumference growth rates was present. Higher maternal early-pregnancy non-fasting glucose levels were also associated with an increased risk of delivering a large-for-gestational-age infant, but decreased risk of delivering a small-for-gestational-age infant (OR 1.28 [95% CI 1.16, 1.41], OR 0.88 [95% CI 0.79, 0.98] per mmol/l increase in maternal early-pregnancy non-fasting glucose levels, respectively). These associations were not explained by maternal sociodemographic factors, lifestyle factors or BMI. Maternal early-pregnancy non-fasting glucose levels were not associated with preterm birth or delivery complications. CONCLUSIONS/INTERPRETATION Higher maternal early-pregnancy non-fasting glucose levels are associated with decreased fetal growth rates in mid-pregnancy and increased fetal growth rates from late pregnancy onwards, and an increased risk of delivering a large-for-gestational-age infant. Future preventive strategies need to focus on screening for an impaired maternal glucose metabolism from preconception and early pregnancy onwards to improve birth outcomes.
Madelon L Geurtsen, Eef E L van Soest, Ellis Voerman, Eric A P Steegers, Vincent W V Jaddoe, Romy Gaillard,
Causes and Prevention
Diabetes
Nov
11
Birthweight in offspring and cardiovascular mortality in their parents, aunts and uncles: a family-based cohort study of 1.35 million births.
Abstract
BACKGROUND A link between suboptimal fetal growth and higher risk of cardiovascular disease (CVD) is well documented. It has been difficult to assess the contribution of environmental versus genetic factors to the association, as these factors are closely connected in nuclear families. We investigated the association between offspring birthweight and CVD mortality in parents, aunts and uncles, and examined whether these associations are explained by CVD risk factors. METHODS We linked Norwegian data from the Medical Birth Registry, the Cause of Death Registry and cardiovascular surveys. A total of 1 353 956 births (1967-2012) were linked to parents and one maternal and one paternal aunt/uncle. Offspring birthweight and CVD mortality association among all relationships was assessed by hazard ratios (HR) from Cox regressions. The influence of CVD risk factors on the associations was examined in a subgroup. RESULTS Offspring birthweight was inversely associated with CVD mortality among parents and aunts/uncles. HR of CVD mortality for one standard deviation (SD) increase in offspring birthweight was 0.72 (0.69-0.75) in mothers and 0.89 (0.86-0.92) in fathers. In aunts/uncles, the HRs were between 0.90 (0.86-0.95) and 0.93 (0.91-0.95). Adjustment for CVD risk factors in a subgroup attenuated all the associations. CONCLUSIONS Birthweight was associated with increased risk of CVD in parents and in aunts/uncles. These associations were largely explained by CVD risk factors. Our findings suggest that associations between offspring birthweight and CVD in adult relatives involve both behavioural variables (especially smoking) and shared genetics relating to established CVD risk factors.
Fareeha Shaikh, Marte Karoline Kjølllesdal, David Carslake, Camilla Stoltenberg, George Davey Smith, Øyvind Næss,
Causes and Prevention
Cardiovascular
Nov
05
Lipid levels achieved after a first myocardial infarction and the prediction of recurrent atherosclerotic cardiovascular disease.
Abstract
BACKGROUND Low density lipoprotein cholesterol (LDL-C) goals post-myocardial infarction (MI) are debated, and the significance of achieved blood lipid levels for predicting a first recurrent atherosclerotic cardiovascular disease (rASCVD) event post-MI is unclear. METHODS This was a cohort study on first-ever MI survivors aged ≤76 years attending 4-14 week revisits throughout Sweden 2005-2013. Personal-level data was collected from SWEDEHEART and linked national registries. Exposures were quintiles of LDL-C, high density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglycerides (TGs) at the revisit. Group level associations with rASCVD (nonfatal MI or coronary heart disease death or fatal or nonfatal ischemic stroke) were estimated in Cox regression models. Predictive capacity was estimated by differences in C-statistic, integrated discriminatory improvement, and net reclassification improvement when adding each blood lipid to a validated risk prediction model. RESULTS 25,643 patients, 96.9% on statin therapy, were followed during a mean of 4.1 years. rASCVD occurred in 2173 patients (8.5%). For LDL-C and TC, moderate associations with rASCVD were observed only in the 5th vs. the lowest (referent) quintiles. For TGs and HDL-C increased risks were observed in quintiles 3-5 vs. the lowest. Minor predictive improvements were observed when lipid fractions were added to the risk model but the discrimination overall was poor (C-statistics <0.6). CONCLUSIONS Our data question the importance of LDL-C levels achieved at first revisit post-MI for decisions on continued treatment intensity considering the weak association with rASCVD observed in this post-MI cohort.
Joel Ohm, Paul Hjemdahl, Per H Skoglund, Andrea Discacciati, Johan Sundström, Kristina Hambraeus, Tomas Jernberg, Per Svensson,
Diagnosis; Prognosis
Cardiovascular
Oct
29
Treatment patterns and associated factors in 14 668 people with type 2 diabetes initiating a second-line therapy: Results from the global DISCOVER study programme.
Abstract
AIM To evaluate treatment data from DISCOVER (NCT02322762 and NCT02226822), a global, prospective, observational study programme of patients with type 2 diabetes initiating a second-line glucose-lowering therapy. MATERIALS AND METHODS Data were collected using a standardized case report form. First- and second-line treatments were assessed in 14 668 patients from 37 countries across six regions. Among patients prescribed first-line metformin monotherapy, Firth logistic regression models were used to assess factors associated with second-line treatment choices. RESULTS The most common first-line therapies were metformin monotherapy (57.9%) and combinations of metformin with a sulphonylurea (14.6%). The most common second-line therapies were combinations of metformin with other agents (72.2%), including dipeptidyl peptidase-4 (DPP-4) inhibitors (25.1%) or sulphonylureas (21.3%). Among patients prescribed first-line metformin monotherapy, the most common second-line therapies were combinations of metformin with a DPP-4 inhibitor [32.8%; across-region range (ARR): 2.4%-51.3%] or a sulphonylurea (30.0%; ARR: 18.3%-63.6%); only a few patients received combinations of metformin with sodium-glucose co-transporter-2 inhibitors (6.7%; ARR: 0.0%-10.8%) or glucagon-like peptide-1 receptor agonists (1.9%; ARR: 0.1%-4.5%). Both clinical and non-medical factors were associated with choice of second-line therapy after metformin monotherapy. CONCLUSIONS Fewer patients than expected received metformin monotherapy at first line, and the use of newer therapies at second line was uncommon in some regions of the world. Patients' socioeconomic status was associated with treatment patterns, suggesting that therapy choices are influenced by cost and access.
Antonio Nicolucci, Bernard Charbonnel, Marília B Gomes, Kamlesh Khunti, Mikhail Kosiborod, Marina V Shestakova, Iichiro Shimomura, Hirotaka Watada, Hungta Chen, Javier Cid-Ruzafa, Peter Fenici, Niklas Hammar, Filip Surmont, Fengming Tang, Stuart Pocock,
Treatment / Management
Diabetes
Oct
21
Factors associated with stillbirth in women with diabetes.
Abstract
AIMS/HYPOTHESIS Stillbirth risk is increased in pregnancy complicated by diabetes. Fear of stillbirth has major influence on obstetric management, particularly timing of delivery. We analysed population-level data from Scotland to describe timing of stillbirths in women with diabetes and associated risk factors. METHODS A retrospective cohort of singleton deliveries to mothers with type 1 (n = 3778) and type 2 diabetes (n = 1614) from 1 April 1998 to 30 June 2016 was analysed using linked routine care datasets. Maternal and fetal characteristics, HbA data and delivery timing were compared between stillborn and liveborn groups. RESULTS Stillbirth rates were 16.1 (95% CI 12.4, 20.8) and 22.9 (95% CI 16.4, 31.8) per 1000 births in women with type 1 (n = 61) and type 2 diabetes (n = 37), respectively. In women with type 1 diabetes, higher HbA before pregnancy (OR 1.03 [95% CI 1.01, 1.04]; p = 0.0003) and in later pregnancy (OR 1.06 [95% CI 1.04, 1.08]; p < 0.0001) were associated with stillbirth, while in women with type 2 diabetes, higher maternal BMI (OR 1.07 [95% CI 1.01, 1.14]; p = 0.02) and pre-pregnancy HbA (OR 1.02 [95% CI 1.00, 1.04]; p = 0.016) were associated with stillbirth. Risk was highest in infants with birthweights <10th centile (sixfold higher born to women with type 1 diabetes [n = 5 stillbirths, 67 livebirths]; threefold higher for women with type 2 diabetes [n = 4 stillbirths, 78 livebirths]) compared with those in the 10th-90th centile (n = 20 stillbirths, 1685 livebirths). Risk was twofold higher in infants with birthweights >95th centile born to women with type 2 diabetes (n = 15 stillbirths, 402 livebirths). A high proportion of stillborn infants were male among mothers with type 2 diabetes (81.1% vs 50.5% livebirths, p = 0.0002). A third of stillbirths occurred at term, with highest rates in the 38th week (7.0 [95% CI 3.7, 12.9] per 1000 ongoing pregnancies) among mothers with type 1 diabetes and in the 39th week (9.3 [95% CI 2.4, 29.2]) for type 2 diabetes. CONCLUSIONS/INTERPRETATION Maternal blood glucose levels and BMI are important modifiable risk factors for stillbirth in diabetes. Babies at extremes of weight centiles are at most risk. Many stillbirths occur at term and could potentially be prevented by change in routine care and delivery policies.
Sharon T Mackin, Scott M Nelson, Sarah H Wild, Helen M Colhoun, Rachael Wood, Robert S Lindsay, ,
Diagnosis; Prognosis, Treatment / Management
Diabetes
Oct
14
Eligibility and subsequent burden of cardiovascular disease of four strategies for blood pressure-lowering treatment: a retrospective cohort study.
Abstract
BACKGROUND Worldwide treatment recommendations for lowering blood pressure continue to be guided predominantly by blood pressure thresholds, despite strong evidence that the benefits of blood pressure reduction are observed in patients across the blood pressure spectrum. In this study, we aimed to investigate the implications of alternative strategies for offering blood pressure treatment, using the UK as an illustrative example. METHODS We did a retrospective cohort study in primary care patients aged 30-79 years without cardiovascular disease, using data from the UK's Clinical Practice Research Datalink linked to Hospital Episode Statistics and Office for National Statistics mortality. We assessed and compared four different strategies to determine eligibility for treatment: using 2011 UK National Institute for Health and Care Excellence (NICE) guideline, or proposed 2019 NICE guideline, or blood pressure alone (threshold ≥140/90 mm Hg), or predicted 10-year cardiovascular risk alone (QRISK2 score ≥10%). Patients were followed up until the earliest occurrence of a cardiovascular disease diagnosis, death, or end of follow-up period (March 31, 2016). For each strategy, we estimated the proportion of patients eligible for treatment and number of cardiovascular events that could be prevented with treatment. We then estimated eligibility and number of events that would occur during 10 years in the UK general population. FINDINGS Between Jan 1, 2011, and March 31, 2016, 1 222 670 patients in the cohort were followed up for a median of 4·3 years (IQR 2·5-5·2). 271 963 (22·2%) patients were eligible for treatment under the 2011 NICE guideline, 327 429 (26·8%) under the proposed 2019 NICE guideline, 481 859 (39·4%) on the basis of a blood pressure threshold of 140/90 mm Hg or higher, and 357 840 (29·3%) on the basis of a QRISK2 threshold of 10% or higher. During follow-up, 32 183 patients were diagnosed with cardiovascular disease (overall rate 7·1 per 1000 person-years, 95% CI 7·0-7·2). Cardiovascular event rates in patients eligible for each strategy were 15·2 per 1000 person-years (95% CI 15·0-15·5) under the 2011 NICE guideline, 14·9 (14·7-15·1) under the proposed 2019 NICE guideline, 11·4 (11·3-11·6) with blood pressure threshold alone, and 16·9 (16·7-17·1) with QRISK2 threshold alone. Scaled to the UK population, we estimated that 233 152 events would be avoided under the 2011 NICE guideline (28 patients needed to treat for 10 years to avoid one event), 270 233 under the 2019 NICE guideline (29 patients), 301 523 using a blood pressure threshold (38 patients), and 322 921 using QRISK2 threshold (27 patients). INTERPRETATION A cardiovascular risk-based strategy (QRISK2 ≥10%) could prevent over a third more cardiovascular disease events than the 2011 NICE guideline and a fifth more than the 2019 NICE guideline, with similar efficiency regarding number treated per event avoided. FUNDING National Institute for Health Research.
Emily Herrett, Sarah Gadd, Rod Jackson, Krishnan Bhaskaran, Elizabeth Williamson, Tjeerd van Staa, Reecha Sofat, Adam Timmis, Liam Smeeth,
Diagnosis; Prognosis, Treatment / Management
Cardiovascular
Oct
08
BMI, Weight Change, and Dementia Risk in Patients With New-Onset Type 2 Diabetes: A Nationwide Cohort Study.
Abstract
OBJECTIVE This study examined the association between baseline BMI, percentage weight change, and the risk of dementia in patients newly diagnosed with type 2 diabetes. RESEARCH DESIGN AND METHODS Using the South Korean National Health Insurance Service-National Health Screening Cohort database, we identified 167,876 subjects aged ≥40 years diagnosed with new-onset type 2 diabetes between 2007 and 2012. Their weight changes were monitored for ∼2 years after diagnosis, with follow-up assessments occurring for an average of 3.5 years. The hazard ratios (HRs) and Bonferroni-adjusted 95% CIs of all-cause dementia, Alzheimer disease (AD), and vascular dementia were estimated using multivariable Cox proportional hazards regression models. RESULTS We identified 2,563 incident dementia cases during follow-up. Baseline BMI among patients with new-onset type 2 diabetes was inversely associated with the risk of all-cause dementia and AD, independent of confounding variables ( for trend <0.001). The percentage weight change during the 2 years after a diagnosis of type 2 diabetes showed significant U-shaped associations with the risk of all-cause dementia development ( < 0.001); the HRs of the disease increased significantly when weight loss or gain was >10% (1.34 [95% CI 1.11-1.63] and 1.38 [1.08-1.76], respectively). Additionally, weight loss >10% was associated with an increased risk of AD (HR 1.26 [95% CI 1.01-1.59]). CONCLUSIONS A lower baseline BMI was associated with increased risks of all-cause dementia and AD in patients with new-onset type 2 diabetes. Weight loss or weight gain after the diagnosis of diabetes was associated with an increased risk of all-cause dementia. Weight loss was associated with an increased risk of AD.
Ga Eun Nam, Yong Gyu Park, Kyungdo Han, Mee Kyoung Kim, Eun Sil Koh, Eun Sook Kim, Min-Kyung Lee, Bongsung Kim, Oak-Kee Hong, Hyuk-Sang Kwon,
Prevalence, Treatment / Management
Diabetes, Kidney disease
Oct
02
Association of Conventional Cardiovascular Risk Factors With Cardiovascular Disease After Hypertensive Disorders of Pregnancy: Analysis of the Nord-Trøndelag Health Study.
Abstract
Importance Women with a history of hypertensive disorders of pregnancy (HDP) have higher risk of cardiovascular disease (CVD). It is not known how much of the excess CVD risk in women with a history of HDP is associated with conventional cardiovascular risk factors. Objective To quantify the excess risk of CVD in women with a history of HDP and estimate the proportion associated with conventional cardiovascular risk factors. Design, Setting, and Participants Prospective cohort study with a median follow-up of 18 years. Population-based cohort of women participating in the Nord-Trøndelag Health Study in Norway. We linked data for 31 364 women from the Nord-Trøndelag Health Study (1984-2008) to validated hospital records (1987-2015), the Cause of Death Registry (1984-2015), and the Medical Birth Registry of Norway (1967-2012). A total of 7399 women were excluded based on selected pregnancy characteristics, incomplete data, or because of emigrating or experiencing the end point before start of follow-up, leaving 23 885 women for study. Data were analyzed between January 1, 2018, and June 6, 2018. Exposures Experiencing 1 or more pregnancies complicated by HDP before age 40 years vs only experiencing normotensive pregnancies. Main Outcomes and Measures We used Cox proportional hazards models to estimate the hazard ratios (HRs) for the association between HDP and CVD. The proportion of excess risk associated with conventional cardiovascular risk factors was estimated using an inverse odds ratio weighting approach. Results Our study population consisted of 23 885 parous women from Nord-Trøndelag County, Norway. A total of 21 766 women had only normotensive pregnancies, while 2199 women experienced ever having an HDP. From age 40 to 70 years, women with history of HDP had an increased risk of CVD compared with women with only normotensive pregnancies (HR, 1.57; 95% CI, 1.32-1.87) but not at older age (β = 0.98; 95% CI, 0.96-1.00; P for interaction by age = .01). Blood pressure and body mass index were associated with up to 77% of the excess risk of CVD in women with history of HDP, while glucose and lipid levels were associated with smaller proportions. Conclusion and Relevance In this study, the risk of excess CVD in women with history of HDP was associated with conventional cardiovascular risk factors, indicating that these risk factors are important targets for cardiovascular prevention in these women.
Eirin B Haug, Julie Horn, Amanda R Markovitz, Abigail Fraser, Bjørnar Klykken, Håvard Dalen, Lars J Vatten, Pål R Romundstad, Janet W Rich-Edwards, Bjørn O Åsvold,
Prevalence
Cardiovascular
Sep
25
Risk of cardiovascular events associated with dipeptidyl peptidase-4 inhibitors in patients with diabetes with and without chronic kidney disease: A nationwide cohort study.
Abstract
BACKGROUND Cardiovascular events associated with oral hypoglycemic agents (OHAs) have raised significant safety concerns. This study assessed the association between dipeptidyl peptidase-4 inhibitors (DPP-4i) and the risk of cardiovascular events in patients with type 2 diabetes mellitus with or without chronic kidney disease (CKD). STUDY DESIGN A retrospective cohort study using Taiwan's National Health Insurance Research Database. SETTINGS AND PARTICIPANTS Our study included patients with type 2 diabetes who received OHAs between March 1, 2009, and December 31, 2012. All eligible subjects were classified into CKD and non-CKD cohorts and further categorized as the DPP-4i and non-DPP-4i users in each cohort. METHODS The DPP-4i and non-DPP-4i groups were matched 1:1 by propensity score to attenuate potential selection bias. Propensity score was estimated by logistic regression, using demographics, co-medications, comorbidities. and adapted diabetic complication severity index at baseline. OUTCOMES Outcomes of interest included a composite endpoint of ischemic stroke, myocardial infarction, cardiovascular death (major adverse cardiac events [MACE]), and hospitalization for heart failure (hHF). COX proportional hazard models were applied to examine the association between DPP-4i and outcomes of interest. RESULTS We identified 37,641 and 87,604 patients with type 2 diabetes with and without CKD, respectively. After propensity score matching, 8,213 pairs of CKD patients and 12,313 pairs of non-CKD patients were included for analysis. In the CKD cohort, DPP-4i were associated with a 25% increased risk of hHF (DPP-4i vs. non-DPP-4i incidence/1,000 person-years: 15.0 vs. 9.9, HR = 1.25; 95% CI 1.01-1.54, p = 0.037) but not with the risk of MACE (HR = 0.89, p = 0.144). In the non-CKD cohort, DPP-4i were associated with a lower risk of MACE (DPP-4i vs. non-DPP-4i incidence/1,000 person-years: 9.8 vs. 12.6 HR = 0.73; 95% CI 0.61-0.87, p = 0.0007), but not the risk of hHF (HR = 1.09, p = 0.631). CONCLUSIONS DPP-4i were found to be associated with decreased risk of MACE in the non-CKD cohort in our study. However, DPP-4i were associated with increased risk of hHF in the CKD cohort. DPP-4i in the CKD cohort should be used cautiously.
Tzu-Lan Huang, Fei-Yuan Hsiao, Chih-Kang Chiang, Li-Jiuan Shen, Chih-Fen Huang,
Treatment / Management
Cardiovascular, Diabetes, Kidney disease
Sep
17
Risk Factors for Atrial Fibrillation in People With Type 1 Diabetes: An Observational Cohort Study of 36,258 Patients From the Swedish National Diabetes Registry.
Abstract
OBJECTIVE This study identified variables associated with increased risk of atrial fibrillation in people with type 1 diabetes. RESEARCH DESIGN AND METHODS We performed a cohort study of people with type 1 diabetes from the Swedish National Diabetes Registry followed up between 1 January 2001 and 31 December 2013. Median follow-up was 9.7 years (interquartile range 5.2-13.0). The association between potential risk factors and incident atrial fibrillation was investigated using adjusted Cox regression. To compare the impact of each risk factor, the gradient of risk per 1 SD was estimated. RESULTS In this cohort of 36,258 patients with type 1 diabetes, 749 developed atrial fibrillation during follow-up. Older age, male sex, renal complications, increased BMI and HbA, coronary artery disease, heart failure, and heart valve disease increased the risk of atrial fibrillation. Age, signs of renal dysfunction with macroalbuminuria, and decreasing estimated glomerular filtration rate were associated with the highest gradient of risk for atrial fibrillation. High blood pressure, severe obesity (BMI >35 kg/m), and elevated levels of HbA (>9.6%) were associated with increased risk, but no associations were found with hyperlipidemia or smoking. CONCLUSIONS The most prominent risk factors for atrial fibrillation in people with type 1 diabetes were older age, cardiovascular comorbidities, and renal complications, while obesity, hypertension, and hyperglycemia had more modest affects.
Sara Hallström, Aldina Pivodic, Annika Rosengren, Arndís F Ólafsdóttir, Ann-Marie Svensson, Marcus Lind,
Prevalence
Cardiovascular, Diabetes
Sep
03
Incidence of type 2 diabetes mellitus in men receiving steroid 5α-reductase inhibitors: population based cohort study.
Abstract
OBJECTIVE To investigate the incidence of new onset type 2 diabetes mellitus in men receiving steroid 5α-reductase inhibitors (dutasteride or finasteride) for long term treatment of benign prostatic hyperplasia. DESIGN Population based cohort study. SETTING UK Clinical Practice Research Datalink (CPRD; 2003-14) and Taiwanese National Health Insurance Research Database (NHIRD; 2002-12). PARTICIPANTS Men in the CPRD who received dutasteride (n=8231), finasteride (n=30 774), or tamsulosin (n=16 270) were evaluated. Propensity score matching (2:1; dutasteride to finasteride or tamsulosin) produced cohorts of 2090, 3445, and 4018, respectively. In the NHIRD, initial numbers were 1251 (dutasteride), 4194 (finasteride), and 86 263 (tamsulosin), reducing to 1251, 2445, and 2502, respectively, after propensity score matching. MAIN OUTCOMES MEASURE Incident type 2 diabetes using a Cox proportional hazard model. RESULTS In the CPRD, 2081 new onset type 2 diabetes events (368 dutasteride, 1207 finasteride, and 506 tamsulosin) were recorded during a mean follow-up time of 5.2 years (SD 3.1 years). The event rate per 10 000 person years was 76.2 (95% confidence interval 68.4 to 84.0) for dutasteride, 76.6 (72.3 to 80.9) for finasteride, and 60.3 (55.1 to 65.5) for tamsulosin. There was a modest increased risk of type 2 diabetes for dutasteride (adjusted hazard ratio 1.32, 95% confidence interval 1.08 to 1.61) and finasteride (1.26, 1.10 to 1.45) compared with tamsulosin. Results for the NHIRD were consistent with the findings for the CPRD (adjusted hazard ratio 1.34, 95% confidence interval 1.17 to 1.54 for dutasteride, and 1.49, 1.38 to 1.61 for finasteride compared with tamsulosin). Propensity score matched analyses showed similar results. CONCLUSIONS The risk of developing new onset type 2 diabetes appears to be higher in men with benign prostatic hyperplasia exposed to 5α-reductase inhibitors than in men receiving tamsulosin, but did not differ between men receiving dutasteride and those receiving finasteride. Additional monitoring might be required for men starting these drugs, particularly in those with other risk factors for type 2 diabetes.
Li Wei, Edward Chia-Cheng Lai, Yea-Huei Kao-Yang, Brian R Walker, Thomas M MacDonald, Ruth Andrew,
Treatment / Management
Diabetes
Aug
31
The effect of dapagliflozin on glycaemic control and other cardiovascular disease risk factors in type 2 diabetes mellitus: a real-world observational study.
Abstract
AIMS/HYPOTHESIS Dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, is indicated for improving glycaemic control in type 2 diabetes mellitus. Whether its effects on HbA and other variables, including safety outcomes, in clinical trials are obtained in real-world practice needs to be established. METHODS We used data from the comprehensive national diabetes register, the Scottish Care Information-Diabetes (SCI-Diabetes) collaboration database, available from 2004 to mid-2016. Data within this database were linked to mortality data from the General Registrar, available from the Information Services Division (ISD) of the National Health Service in Scotland. We calculated crude within-person differences between pre- and post-drug-initiation values of HbA, BMI, body weight, systolic blood pressure (SBP) and eGFR. We used mixed-effects regression models to adjust for within-person time trajectories in these measures. For completeness, we evaluated safety outcomes, cardiovascular disease events, lower-limb amputation and diabetic ketoacidosis, focusing on cumulative exposure effects, using Cox proportional hazard models, though power to detect such effects was limited. RESULTS Among 8566 people exposed to dapagliflozin over a median of 210 days the crude within-person change in HbA was -10.41 mmol/mol (-0.95%) after 3 months' exposure. The crude change after 12 months was -12.99 mmol/mol (-1.19%) but considering the expected rise over time in HbA gave a dapagliflozin-exposure-effect estimate of -15.14 mmol/mol (95% CI -15.87, -14.41) (-1.39% [95% CI -1.45, -1.32]) at 12 months that was maintained thereafter. A drop in SBP of -4.32 mmHg (95% CI -4.84, -3.79) on exposure within the first 3 months was also maintained thereafter. Reductions in BMI and body weight stabilised by 6 months at -0.82 kg/m (95% CI -0.87, -0.77) and -2.20 kg (95% CI -2.34, -2.06) and were maintained thereafter. eGFR declined initially by -1.81 ml min [1.73 m] (95% CI -2.10, -1.52) at 3 months but varied thereafter. There were no significant effects of cumulative drug exposure on safety outcomes. CONCLUSIONS/INTERPRETATION Dapagliflozin exposure was associated with reductions in HbA, SBP, body weight and BMI that were at least as large as in clinical trials. Dapagliflozin also prevented the expected rise in HbA and SBP over the period of study.
Stuart J McGurnaghan, Liam Brierley, Thomas M Caparrotta, Paul M McKeigue, Luke A K Blackbourn, Sarah H Wild, Graham P Leese, Rory J McCrimmon, John A McKnight, Ewan R Pearson, John R Petrie, Naveed Sattar, Helen M Colhoun, ,
Treatment / Management
Cardiovascular, Diabetes
Aug
07
Anesthetic type and hospital outcomes after carotid endarterectomy from the Vascular Quality Initiative database
Abstract
OBJECTIVE Studies on the safety of carotid endarterectomy (CEA) under different anesthetic techniques are sometimes contradictory. The aim of this study was to compare real-world outcomes of CEA under general anesthesia (GA) vs regional or local anesthesia (RA/LA). METHODS A retrospective analysis of the Vascular Quality Initiative database (2003-2017) was performed. Primary outcomes included perioperative stroke, death, and myocardial infarction (MI) occurring during the hospital stay. Univariate and multivariate analyses were used. To minimize selection bias and to evaluate comparable groups, patients were matched on baseline variables using coarsened exact matching. RESULTS Of 75,319 CEA cases, 6684 (8.9%) were performed under RA/LA. These patients were more likely to be older (median age, 72 vs 71 years) and male (62.5% vs 60.2%), with higher American Society of Anesthesiologists class (class 3-5, 94.2% vs 93.0%) than those undergoing CEA-GA (all P < .001). CEA-GA had higher crude rates of in-hospital cardiac outcomes including MI mainly diagnosed clinically or on electrocardiography (0.5% vs 0.2%; P = .01), dysrhythmia (1.6% vs 1.2%; P < .001), acute congestive heart failure (CHF; 0.5% vs 0.2%; P < .001), and hemodynamic instability (27.0% vs 20.0%; P < .001) compared with CEA-RA/LA. No difference in perioperative stroke or death was seen between the two groups. On multivariate analysis, CEA-GA was associated with twice the odds of in-hospital MI (adjusted odds ratio [aOR], 1.95; 95% confidence interval [CI], 1.06-3.59; P = .03), 4 times the odds of acute CHF (aOR, 3.92; 95% CI, 1.84-8.34; P < .001), and 1.5 times the odds of hemodynamic instability (aOR, 1.54; 95% CI, 1.44-1.66; P < .001). Patients undergoing CEA-GA had 1.8 times the odds of staying in the hospital for >1 day (aOR, 1.80; 95% CI, 1.67-1.93; P < .001). Coarsened exact matching confirmed our results. Risk factors associated with increased cardiac complications (MI and CHF) under GA included female gender, increased age, Medicaid insurance, history of smoking, medical comorbidities (such as hypertension, diabetes, coronary artery disease, and CHF), prior ipsilateral carotid intervention, and urgent/emergent procedures. CONCLUSIONS Patients undergoing CEA under GA have higher odds of postoperative MI, acute CHF, and hemodynamic instability compared with those undergoing CEA under RA/LA. They are also more likely to stay in the hospital for >1 day. However, the overall risk of cardiac adverse events after CEA was low, which made the differences clinically irrelevant. The choice of anesthesia approach to CEA should be driven by the team's experience and the patient's risk factors and preference.
Dakour Aridi, Hanaa Paracha, Nawar Nejim, Besma Locham, Satinderjit Malas, Mahmoud B
Treatment / Management
Cardiovascular
Aug
08
Glucagon-Like Peptide 1 Receptor Agonists and the Risk of Incident Diabetic Retinopathy.
Abstract
OBJECTIVE Previous studies suggested that glucagon-like peptide 1 receptor agonists (GLP-1 RAs) may initially worsen and possibly increase the risk of diabetic retinopathy. However, data on this possible association remain limited. Thus, this population-based study aimed to determine whether use of GLP-1 RAs is associated with an increased risk of incident diabetic retinopathy. RESEARCH DESIGN AND METHODS Using the U.K. Clinical Practice Research Datalink (CPRD), we conducted a cohort study among 77,115 patients with type 2 diabetes initiating antidiabetic drugs between January 2007 and September 2015. Adjusted hazard ratios (HRs) and 95% CIs of incident diabetic retinopathy were estimated using time-dependent Cox proportional hazards models, comparing use of GLP-1 RAs with current use of two or more oral antidiabetic drugs. In an ancillary analysis, new users of GLP-1 RAs were compared with new users of insulin. RESULTS During 245,825 person-years of follow-up, 10,763 patients were newly diagnosed with diabetic retinopathy. Compared with current use of two or more oral antidiabetic drugs, use of GLP-1 RAs was not associated with an increased risk of incident diabetic retinopathy overall (HR 1.00, 95% CI 0.85-1.17). Compared with insulin, GLP-1 RAs were associated with a decreased risk of diabetic retinopathy (HR 0.67, 95% CI 0.51-0.90). CONCLUSIONS The associations with diabetic retinopathy varied according to the type of comparator. When compared with use of two or more oral antidiabetic drugs, use of GLP-1 RAs was not associated with an increased risk of incident diabetic retinopathy. The apparent lower risk of diabetic retinopathy associated with GLP-1 RAs compared with insulin may be due to residual confounding.
Antonios Douros, Kristian B Filion, Hui Yin, Oriana Hoi Yu, Mahyar Etminan, Jacob A Udell, Laurent Azoulay,
Treatment / Management
Diabetes
Jul
11
Real-World Data of Prasugrel vs. Ticagrelor in Acute Myocardial Infarction: Results from the RENAMI Registry.
Abstract
BACKGROUND Limited data are available concerning differences in clinical outcomes for real-life patients treated with ticagrelor versus prasugrel after percutaneous coronary intervention (PCI). OBJECTIVE Our objective was to determine and compare the efficacy and safety of ticagrelor and prasugrel in a real-world population. METHODS RENAMI was a retrospective, observational registry including the data and outcomes of consecutive patients with acute coronary syndrome (ACS) who underwent primary PCI and were discharged with dual antiplatelet therapy (DAPT) between January 2012 and January 2016. The mean follow-up period was 17 ± 9 months. In total, 11 university hospitals from six European countries participated. After propensity-score matching, there were no substantial differences in the baseline clinical and interventional features. All patients were treated with acetylsalicylic acid plus prasugrel 10 mg once daily or acetylsalicylic acid plus ticagrelor 90 mg twice daily. Mean duration of DAPT was 12.04 ± 3.4 months with prasugrel and 11.90 ± 4.1 months with ticagrelor (p = 0.47). The primary and secondary endpoints were long-term net adverse clinical events (NACE) and major adverse cardiovascular events (MACE), respectively, along with their single components. Subgroup analysis for freedom from NACE and MACE was performed according to length of DAPT and clinical presentation [ST-elevation myocardial infarction (STEMI)-ACS versus non-ST-elevation myocardial infarction (NSTEMI)-ACS]. RESULTS In total, 4424 patients (2725 ticagrelor, 1699 prasugrel) were enrolled. After propensity-score matching, 1290 patients in each cohort were included in the analysis. At 12 months, the incidence of both NACE and MACE was lower with prasugrel (NACE: 5.3% vs. 8.5% [p = 0.001]; MACE: 5% vs. 8.1% [p =  0.001]) mainly driven by a reduction in recurrent myocardial infarction (MI) (2.4 vs. 4.0%; p = 0.029) and a lower rate of Bleeding Academic Research Consortium (BARC) 3-5 bleeding (1.5 vs. 2.9%; p = 0.011). The benefit of prasugrel was confirmed for patients with NSTEMI and for those discharged with a DAPT regimen of ≤ 12 months. Only a trend in the reduction of NACE and MACE was noted for STEMI or for those treated with longer DAPT. CONCLUSIONS Comparison of these drugs suggested that prasugrel is safer and more efficacious than ticagrelor in combination with aspirin after NSTEMI but not STEMI. No differences were found for events occurring after 12 months. The nonrandomized design of the present research means further studies are required to support these findings.
Ovidio De Filippo, Martina Cortese, Fabrizio D Ascenzo, Sergio Raposeiras-Roubin, Emad Abu-Assi, Tim Kinnaird, Albert Ariza-Solé, Sergio Manzano-Fernández, Christian Templin, Lazar Velicki, Ioanna Xanthopoulou, Enrico Cerrato, Andrea Rognoni, Giacomo Boccuzzi, Antonio Montefusco, Andrea Montabone, Salma Taha, Alessandro Durante, Sebastiano Gili, Giulia Magnani, Michele Autelli, Alberto Grosso, Pedro Flores Blanco, Alberto Garay, Giorgio Quadri, Ferdinando Varbella, Berenice Caneiro Queija, Rafael Cobas Paz, María Cespón Fernández, Isabel Muñoz Pousa, Diego Gallo, Umberto Morbiducci, Alberto Dominguez-Rodriguez, Mariano Valdés, Angel Cequier, Dimitrios Alexopoulos, Andrés Iñiguez-Romo, Mauro Rinaldi,
Treatment / Management
Cardiovascular
Jul
11
Risk of Mortality and Hospitalization After Post-Pancreatitis Diabetes Mellitus vs Type 2 Diabetes Mellitus: A Population-Based Matched Cohort Study.
Abstract
OBJECTIVES To investigate the risk of mortality and hospitalization in individuals with post-pancreatitis diabetes mellitus (PPDM) compared with those with type 2 diabetes mellitus (T2DM). METHODS Using nationwide hospital discharge data on pancreatitis and diabetes in New Zealand (n = 231,943), a total of 959 individuals with PPDM were identified. For each individual with PPDM, 10 age- and sex-matched individuals with T2DM were randomly selected. Multivariable Cox regression analysis was conducted, and the risk was expressed as hazard ratio (HR) and 95% confidence interval (CI). RESULTS A total of 3,867 deaths occurred among 10,549 study individuals. Individuals with PPDM had all-cause mortality rate at 80.5 (95% CI, 70.3-90.6) per 1,000 person-years, which was higher compared with T2DM individuals (adjusted HR, 1.13 (95% CI, 1.00-1.29); absolute excess risk, 14.8 (95% CI, 4.5-25.2) per 1,000 person-years). Compared with T2DM, PPDM was associated with higher risks of mortality from cancer (adjusted HR, 1.44; 95% CI, 1.13-1.83), infectious disease (adjusted HR, 2.52; 95% CI, 1.69-3.77), and gastrointestinal disease (adjusted HR, 2.56; 95% CI, 1.64-4.01). Individuals with PPDM vs T2DM were also at significantly higher risks of hospitalization for chronic pulmonary disease, moderate to severe renal disease, and infectious disease. CONCLUSIONS Individuals with PPDM have higher risk of mortality and hospitalization compared with individuals with T2DM. Guidelines for management of PPDM need to be developed with a view to preventing excess deaths and hospitalizations in individuals with PPDM.
Jaelim Cho, Robert Scragg, Maxim S Petrov,
Causes and Prevention
Diabetes
Jul
09
Sub-optimal cholesterol response to initiation of statins and future risk of cardiovascular disease.
Abstract
OBJECTIVE To assess low-density lipoprotein cholesterol (LDL-C) response in patients after initiation of statins, and future risk of cardiovascular disease (CVD). METHODS Prospective cohort study of 165 411 primary care patients, from the UK Clinical Practice Research Datalink, who were free of CVD before statin initiation, and had at least one pre-treatment LDL-C within 12 months before, and one post-treatment LDL-C within 24 months after, statin initiation. Based on current national guidelines, <40% reduction in baseline LDL-C within 24 months was classified as a sub-optimal statin response. Cox proportional regression and competing-risks survival regression models were used to determine adjusted hazard ratios (HRs) and sub-HRs for incident CVD outcomes for LDL-C response to statins. RESULTS 84 609 (51.2%) patients had a sub-optimal LDL-C response to initiated statin therapy within 24 months. During 1 077 299 person-years of follow-up (median follow-up 6.2 years), there were 22 798 CVD events (12 142 in sub-optimal responders and 10 656 in optimal responders). In sub-optimal responders, compared with optimal responders, the HR for incident CVD was 1.17 (95% CI 1.13 to 1.20) and 1.22 (95% CI 1.19 to 1.25) after adjusting for age and baseline untreated LDL-C. Considering competing risks resulted in lower but similar sub-HRs for both unadjusted (1.13, 95% CI 1.10 to 1.16) and adjusted (1.19, 95% CI 1.16 to 1.23) cumulative incidence function of CVD. CONCLUSIONS Optimal lowering of LDL-C is not achieved within 2 years in over half of patients in the general population initiated on statin therapy, and these patients will experience significantly increased risk of future CVD.
Ralph Kwame Akyea, Joe Kai, Nadeem Qureshi, Barbara Iyen, Stephen F Weng,
Treatment / Management
Cardiovascular
Jun
27
Pre-eclampsia and risk of later kidney disease: nationwide cohort study.
Abstract
OBJECTIVE To investigate associations between pre-eclampsia and later risk of kidney disease. DESIGN Nationwide register based cohort study. SETTING Denmark. POPULATION All women with at least one pregnancy lasting at least 20 weeks between 1978 and 2015. MAIN OUTCOME MEASURE Hazard ratios comparing rates of kidney disease between women with and without a history of pre-eclampsia, stratified by gestational age at delivery and estimated using Cox regression. RESULTS The cohort consisted of 1 072 330 women followed for 19 994 470 person years (average 18.6 years/woman). Compared with women with no previous pre-eclampsia, those with a history of pre-eclampsia were more likely to develop chronic renal conditions: hazard ratio 3.93 (95% confidence interval 2.90 to 5.33, for early preterm pre-eclampsia (delivery <34 weeks); 2.81 (2.13 to 3.71) for late preterm pre-eclampsia (delivery 34-36 weeks); 2.27 (2.02 to 2.55) for term pre-eclampsia (delivery ≥37 weeks). In particular, strong associations were observed for chronic kidney disease, hypertensive kidney disease, and glomerular/proteinuric disease. Adjustment for cardiovascular disease and hypertension only partially attenuated the observed associations. Stratifying the analyses on time since pregnancy showed that associations between pre-eclampsia and chronic kidney disease and glomerular/proteinuric disease were much stronger within five years of the latest pregnancy (hazard ratio 6.11 (3.84 to 9.72) and 4.77 (3.88 to 5.86), respectively) than five years or longer after the latest pregnancy (2.06 (1.69 to 2.50) and 1.50 (1.19 to 1.88). By contrast, associations between pre-eclampsia and acute renal conditions were modest. CONCLUSION s Pre-eclampsia, particularly early preterm pre-eclampsia, was strongly associated with several chronic renal disorders later in life. More research is needed to determine which women are most likely to develop kidney disease after pre-eclampsia, what mechanisms underlie the association, and what clinical follow-up and interventions (and in what timeframe post-pregnancy) would be most appropriate and effective.
Jonas H Kristensen, Saima Basit, Jan Wohlfahrt, Mette Brimnes Damholt, Heather A Boyd,
Diagnosis; Prognosis
Kidney disease
Jun
18
Association of Diabetes and Glycated Hemoglobin With the Risk of Intracerebral Hemorrhage: A Population-Based Cohort Study.
Abstract
OBJECTIVE To examine the association of diabetes and glycated hemoglobin (HbA) with the risk of intracerebral hemorrhage (ICH) in a large population-based cohort. RESEARCH DESIGN AND METHODS The computerized database of the largest health care provider in Israel was used to identify adult members aged 40 years or older and alive at 1 January 2010 (297,486 with diabetes and 1,167,585 without diabetes). The cohort was followed until 31 December 2017 for incidence of ICH. Multivariable Cox proportional hazards regression models, adjusted for baseline disease risk score, were applied to estimate the hazard ratio (HR) of ICH. RESULTS Overall 4,170 ICH cases occurred during 10,730,915 person-years of follow-up. Diabetes was independently associated with increased ICH risk, with hazard ratio (HR) 1.36 (95% CI 1.27-1.45), and increased with longer diabetes duration: 1.23 (1.12-1.35) and 1.44 (1.34-1.56) for diabetes duration ≤5 years and >5 years, respectively. The increased ICH risk associated with diabetes was more pronounced in patients ≤60 years old ( <0.001). Among patients with diabetes, HbA had a nonlinear J-shaped relationship with ICH ( for nonlinearity = 0.0186). Compared to the fourth HbA decile, 6.5-6.7% (48-50 mmol/mol), the HR for ICH was 1.27 (1.01-1.59) and 2.19 (1.75-2.73) in the lowest HbA decile, ≤6.0% (≤42 mmol/mol), and highest HbA decile, >9.3% (>78 mmol/mol), respectively. CONCLUSIONS Diabetes is associated with increased risk of ICH that is directly associated with diabetes duration. ICH and HbA appear to have a J-shaped relationship, suggesting that both poor control as well as extreme intensive diabetes control might be associated with increased risk.
Walid Saliba, Ofra Barnett-Griness, Naomi Gronich, Jeremy Molad, Jonathan Naftali, Gad Rennert, Eitan Auriel,
Causes and Prevention
Cardiovascular, Diabetes
Jun
11
Sodium glucose cotransporter 2 inhibitors and risk of serious adverse events: nationwide register based cohort study.
Abstract
OBJECTIVE To assess the association between the use of sodium glucose cotransporter 2 (SGLT2) inhibitors and seven serious adverse events of current concern. DESIGN Register based cohort study. SETTING Sweden and Denmark from July 2013 to December 2016. PARTICIPANTS A propensity score matched cohort of 17 213 new users of SGLT2 inhibitors (dapagliflozin, 61%; empagliflozin, 38%; canagliflozin, 1%) and 17 213 new users of the active comparator, glucagon-like peptide 1 (GLP1) receptor agonists. MAIN OUTCOME MEASURES The primary outcomes were lower limb amputation, bone fracture, diabetic ketoacidosis, acute kidney injury, serious urinary tract infection, venous thromboembolism, and acute pancreatitis, as identified from hospital records. Hazard ratios and 95% confidence intervals were estimated by using Cox proportional hazards models. RESULTS Use of SGLT2 inhibitors, as compared with GLP1 receptor agonists, was associated with an increased risk of lower limb amputation (incidence rate 2.7 1.1 events per 1000 person years, hazard ratio 2.32, 95% confidence interval 1.37 to 3.91) and diabetic ketoacidosis (1.3 0.6, 2.14, 1.01 to 4.52) but not with bone fracture (15.4 13.9, 1.11, 0.93 to 1.33), acute kidney injury (2.3 3.2, 0.69, 0.45 to 1.05), serious urinary tract infection (5.4 6.0, 0.89, 0.67 to 1.19), venous thromboembolism (4.2 4.1, 0.99, 0.71 to 1.38) or acute pancreatitis (1.3 1.2, 1.16, 0.64 to 2.12). CONCLUSIONS In this analysis of nationwide registers from two countries, use of SGLT2 inhibitors, as compared with GLP1 receptor agonists, was associated with an increased risk of lower limb amputation and diabetic ketoacidosis, but not with other serious adverse events of current concern.
Peter Ueda, Henrik Svanström, Mads Melbye, Björn Eliasson, Ann-Marie Svensson, Stefan Franzén, Soffia Gudbjörnsdottir, Kristian Hveem, Christian Jonasson, Björn Pasternak,
Treatment / Management
Diabetes
May
23
Real-Life Benefits of Statins for Cardiovascular Prevention in Elderly Subjects: A Population-Based Cohort Study.
Abstract
OBJECTIVES The benefits of initiating statins in the elderly remains debated. We evaluated the effects of initiating statins in the elderly, according to cardiovascular risk. METHODS This population-based cohort study used data of the representative sample of the French health care system database for the 2008-2015 period. New users of statins, aged 75 years and older, were dynamically included in the cohort and matched 1:1 to statin nonusers on age, sex, numbers of different drugs dispensed and medical consultations, and cardiovascular history. Patients were classified into 3 cardiovascular risk groups: secondary prevention (history of coronary heart disease), primary prevention with modifiable risk factors (diabetes or cardiovascular medications), and primary prevention without modifiable risk factors (none of the above). Effect of cumulative use of statins on occurrence of acute coronary syndrome or all-cause death was analyzed by using multivariable time-dependent Cox models stratified on cardiovascular risk at inclusion. RESULTS Among the 7284 patients included, median follow-up was 4.7 years. Cumulative use of statins was associated with a lower risk of outcomes in the primary prevention with modifiable risk factors group (adjusted hazard ratio 0.93 per year of use; 95% confidence interval, 0.89-0.96; P < .01) and in the secondary prevention group (0.75; 0.63-0.90; P < .01), but not in the primary prevention without modifiable risk factors group (1.01; 0.86-1.18; P = .92). CONCLUSIONS Statin treatment was not associated with a reduction in acute coronary syndrome or all-cause death in elderly without modifiable cardiovascular risk factor treated in primary prevention.
Julien Bezin, Nicholas Moore, Yohann Mansiaux, Philippe Gabriel Steg, Antoine Pariente,
Treatment / Management
Cardiovascular
May
02
Association between glycemic control and risk of fracture in diabetic patients: A nested case-control study.
Abstract
Context Diabetes mellitus (DM) is associated with an increased risk of fractures. However, the impact of glycemic control on the risk of fracture is not well understood. Objective To evaluate the association between the level of glycemic control and the risk of low-trauma fractures in patients with type 1 (T1DM) and type 2 (T2DM) diabetes mellitus. Design Nested case-control analysis. Setting UK-based Clinical Practice Research Datalink. Patients or other participants The study population consisted of patients whose T1DM or T2DM was newly diagnosed between 1995 and 2015. Cases were patients with a low-trauma fracture after DM onset. We matched 4 controls to each case on age, sex, general practice, fracture date, and diabetes type and duration. Statistical analysis Conditional logistic regression analyses adjusted for covariates including BMI, smoking, diabetes complications and medications. Results The study population consisted of 3,329 T1DM and 44,275 T2DM patients. Median duration between diabetes onset and fracture date was 4.5 years for both, T1DM and T2DM. The risk of fracture was increased in T1DM patients with mean HbA1c >8.0% (aOR 1.39, 95% CI 1.06-1.83) compared to T1DM patients with mean HbA1c values ≤7.0%. There was no such effect in T2DM patients. Independently of glycemic control, the risk of fracture was elevated in patients with T2DM and current use of rosiglitazone and pioglitazone. Conclusions The impact of glycemic control on the risk of low-trauma fracture differs between T1DM and T2DM patients. Poor glycemic control increased the risk of fracture in T1DM but not in T2DM patients.
Janina Vavanikunnel, Sarah Charlier, Claudia Becker, Cornelia Schneider, Susan S Jick, Christoph R Meier, Christian Meier,
Causes and Prevention, Diagnosis; Prognosis
Diabetes
May
02
Cardiovascular Risk Factor Burden in U.S. People With Incident Type 2 Diabetes Receiving Antidiabetic and Cardioprotective Therapies.
Abstract
OBJECTIVE Individualized treatment of patients with diabetes requires detailed evaluation of risk factor dynamics at the population level. This study evaluated the persistent glycemic and cardiovascular (CV) risk factor burden over 2 years after treatment intensification (TI). RESEARCH DESIGN AND METHODS From U.S. Centricity Electronic Medical Records, 276,884 patients with incident type 2 diabetes who intensified metformin were selected. Systolic blood pressure (SBP) ≥130/140 mmHg and LDL ≥70/100 mg/dL were defined as uncontrolled for those with/without a history of CV disease at TI. Triglycerides ≥150 mg/dL and HbA ≥7.5% (58 mmol/mol) were defined as uncontrolled. Longitudinal measures over 2 years after TI were used to define risk factor burden. RESULTS With 3.7 years' mean follow-up, patients were 59 years, 70% obese, 22% had a history of CV disease; 60, 30, 50, and 48% had uncontrolled HbA, SBP, LDL, and triglycerides, respectively, at TI; and 81% and 69% were receiving antihypertensive(s) and lipid-modifying therapies, respectively. The proportion of patients with consistently uncontrolled HbA increased from 31% in 2005 to 41% in 2014. Among those on lipid-modifying drugs, 41% and 37% had consistently high LDL and triglycerides over 2 years, respectively. Being on antihypertensive therapies, 29% had consistently uncontrolled SBP. Among patients receiving cardioprotective therapies, 63% failed to achieve control in HbA + LDL, 57% in HbA + SBP, 55% in LDL + SBP, and 63% in HbA + triglycerides over 2 years after TI. CONCLUSIONS Among patients on multiple therapies for risk factor control, more than one-third had uncontrolled HbA, lipid, and SBP levels, and more than one-half had two CV risk factors that were simultaneously uncontrolled after TI.
Olga Montvida, Xiaoling Cai, Sanjoy K Paul,
Treatment / Management
Cardiovascular, Diabetes
Apr
30
High lipoprotein(a) and high risk of mortality.
Abstract
Aims Several lipoprotein(a)-lowering therapies are currently being developed with the long-term goal of reducing cardiovascular disease and mortality; however, the relationship between lipoprotein(a) and mortality is unclear. We tested the hypothesis that lipoprotein(a) levels are associated with risk of mortality. Methods and results We studied individuals from two prospective studies of the Danish general population, of which 69 764 had information on lipoprotein(a) concentrations, 98 810 on LPA kringle-IV type 2 (KIV-2) number of repeats, and 119 094 on LPA rs10455872 genotype. Observationally, lipoprotein(a) >93 mg/dL (199 nmol/L; 96th-100th percentiles) vs. <10 mg/dL (18 nmol/L; 1st-50th percentiles) were associated with a hazard ratio of 1.50 (95% confidence interval 1.28-1.76) for cardiovascular mortality and of 1.20 (1.10-1.30) for all-cause mortality. The median survival for individuals with lipoprotein(a) >93 mg/dL (199 nmol/L; 96th-100th percentiles) and ≤93 mg/dL (199 nmol/L; 1st-95th percentiles) were 83.9 and 85.1 years (log rank P = 0.005). For cardiovascular mortality, a 50 mg/dL (105 nmol/L) increase in lipoprotein(a) levels was associated observationally with a hazard ratio of 1.16 (1.09-1.23), and genetically with risk ratios of 1.23 (1.08-1.41) based on LPA KIV2 and of 0.98 (0.88-1.09) based on LPA rs10455872. For all-cause mortality, corresponding values were 1.05 (1.01-1.09), 1.10 (1.04-1.18), and 0.97 (0.92-1.02), respectively. Finally, for a similar cholesterol content increase, lipoprotein(a) was more strongly associated with cardiovascular and all-cause mortality than low-density lipoprotein, implying that the mortality effect of high lipoprotein(a) is above that explained by its cholesterol content. Conclusion High levels of lipoprotein(a), through corresponding low LPA KIV-2 number of repeats rather than through high cholesterol content were associated with high risk of mortality. These findings are novel.
Anne Langsted, Pia R Kamstrup, Børge G Nordestgaard,
Causes and Prevention
Cardiovascular
Apr
30
Net Clinical Benefit of Non-Vitamin K Antagonist vs Vitamin K Antagonist Anticoagulants in Elderly Patients with Atrial Fibrillation.
Abstract
BACKGROUND The risks of thromboembolic and hemorrhagic events in patients with atrial fibrillation both increase with age; therefore, net clinical benefit analyses of anticoagulant treatments in the elderly population are crucial to guide treatment. We evaluated the 1-year clinical outcomes with non-vitamin-K antagonist and vitamin K antagonist oral anticoagulants (NOACs vs VKAs) in elderly (≥75 years) patients with atrial fibrillation in a prospective registry setting. METHODS Data on 3825 elderly patients were pooled from the PREFER in AF and PREFER in AF PROLONGATION registries. The primary outcome was the incidence of the net composite endpoint, including major bleeding and ischemic cardiovascular events on NOACs (n = 1556) compared with VKAs (n = 2269). RESULTS The rates of the net composite endpoint were 6.6%/year with NOACs vs 9.1%/year with VKAs (odds ratio [OR] 0.71; 95% confidence interval [CI], 0.51-0.99; P = .042). NOAC therapy was associated with a lower rate of major bleeding compared with VKA use (OR 0.58; 95% CI, 0.38-0.90; P = .013). Ischemic events were nominally reduced too (OR 0.71; 95% CI, 0.51-1.00; P = .050). Major bleeding with NOACs was numerically lower in higher-risk patients with low body mass index (BMI; OR 0.50; 95% CI, 0.22-1.12; P = .07) or with age ≥85 years (OR 0.44; 95% CI, 0.13-1.49; P = .17). CONCLUSIONS Our real-world data indicate that, compared with VKAs, NOAC use is associated with a better net clinical benefit in elderly patients with atrial fibrillation, primarily due to lower rates of major bleeding. Major bleeding with NOACs was numerically lower also in higher-risk patients with low BMI or age ≥85 years.
Giuseppe Patti, Ladislav Pecen, Markus Lucerna, Kurt Huber, Miklos Rohla, Giulia Renda, Jolanta Siller-Matula, Fabrizio Ricci, Paulus Kirchhof, Raffaele De Caterina,
Treatment / Management
Cardiovascular
Apr
16
Effects of Statin Therapy on the Risk of Intracerebral Hemorrhage in Korean Patients with Hyperlipidemia.
Abstract
STUDY OBJECTIVE Statins are widely used for primary and secondary prevention of cardiovascular and cerebrovascular disease. Several large randomized trials have suggested that statins might increase the risk of intracerebral hemorrhage (ICH); studies have also shown interethnic variability in responses to statins. This study aimed to determine the association between statin use and the risk of ICH in patients with hyperlipidemia among a Korean population. DESIGN Population-based, retrospective cohort study. DATA SOURCE Korean National Health Insurance Service-National Sample Cohort database (2002-2015). PATIENTS A total of 313,368 patients, aged 40-85 years, without a history of hemorrhagic stroke were included after being diagnosed with hyperlipidemia between January 2003 and December 2013 (for follow-up through December 2015). Of those, statin users were compared with nonusers by using propensity score matching in a 1:1 ratio (21,797 in each group). The study groups were matched for age, sex, Charlson Comorbidity Index score, follow-up duration, comorbidities, and concurrent medications. MEASUREMENTS AND MAIN RESULTS The primary endpoint was occurrence of an ICH event. Secondary endpoints were mortality (all-cause, major adverse cardiovascular and cerebrovascular event related, and stroke related) and outcomes after ICH (e.g., recurrent ICH and mortality after primary ICH event). The Cox proportional hazard model was used to evaluate the ICH risk of statins. Subgroup analyses were performed based on ICH-related risk factors. During a mean follow-up period of 6.4 years, ICH occurred in 456 of the 43,594 patients (1.05%). Statin use was significantly associated with a decreased ICH risk (adjusted hazard ratio [aHR] 0.78, 95% confidence interval [CI] 0.65-0.94). Compared with nonusers, statin users showed significantly lower all-cause mortality (aHR 0.61, 95% CI 0.57-0.64), cardiovascular and cerebrovascular disease-related mortality (aHR 0.75, 95% CI 0.65-0.85), and stroke-related mortality (aHR 0.69, 95% CI 0.54-0.88). No significant differences in recurrence and mortality after an ICH event were noted between study groups. CONCLUSION Statin therapy was associated with a decreased ICH risk and improvements in ischemic cardiovascular and cerebrovascular outcomes in Korean patients with hyperlipidemia. Further large-scale clinical studies are needed to clarify the impact of statins on the risk of developing ICH.
Minji Jung, Sukhyang Lee,
Treatment / Management
Cardiovascular
Apr
16
Excess mortality and cardiovascular disease in young adults with type 1 diabetes in relation to age at onset: a nationwide, register-based cohort study.
Abstract
BACKGROUND People with type 1 diabetes are at elevated risk of mortality and cardiovascular disease, yet current guidelines do not consider age of onset as an important risk stratifier. We aimed to examine how age at diagnosis of type 1 diabetes relates to excess mortality and cardiovascular risk. METHODS We did a nationwide, register-based cohort study of individuals with type 1 diabetes in the Swedish National Diabetes Register and matched controls from the general population. We included patients with at least one registration between Jan 1, 1998, and Dec 31, 2012. Using Cox regression, and with adjustment for diabetes duration, we estimated the excess risk of all-cause mortality, cardiovascular mortality, non-cardiovascular mortality, acute myocardial infarction, stroke, cardiovascular disease (a composite of acute myocardial infarction and stroke), coronary heart disease, heart failure, and atrial fibrillation. Individuals with type 1 diabetes were categorised into five groups, according to age at diagnosis: 0-10 years, 11-15 years, 16-20 years, 21-25 years, and 26-30 years. FINDINGS 27 195 individuals with type 1 diabetes and 135 178 matched controls were selected for this study. 959 individuals with type 1 diabetes and 1501 controls died during follow-up (median follow-up was 10 years). Patients who developed type 1 diabetes at 0-10 years of age had hazard ratios of 4·11 (95% CI 3·24-5·22) for all-cause mortality, 7·38 (3·65-14·94) for cardiovascular mortality, 3·96 (3·06-5·11) for non-cardiovascular mortality, 11·44 (7·95-16·44) for cardiovascular disease, 30·50 (19·98-46·57) for coronary heart disease, 30·95 (17·59-54·45) for acute myocardial infarction, 6·45 (4·04-10·31) for stroke, 12·90 (7·39-22·51) for heart failure, and 1·17 (0·62-2·20) for atrial fibrillation. Corresponding hazard ratios for individuals who developed type 1 diabetes aged 26-30 years were 2·83 (95% CI 2·38-3·37) for all-cause mortality, 3·64 (2·34-5·66) for cardiovascular mortality, 2·78 (2·29-3·38) for non-cardiovascular mortality, 3·85 (3·05-4·87) for cardiovascular disease, 6·08 (4·71-7·84) for coronary heart disease, 5·77 (4·08-8·16) for acute myocardial infarction, 3·22 (2·35-4·42) for stroke, 5·07 (3·55-7·22) for heart failure, and 1·18 (0·79-1·77) for atrial fibrillation; hence the excess risk differed by up to five times across the diagnosis age groups. The highest overall incidence rate, noted for all-cause mortality, was 1·9 (95% CI 1·71-2·11) per 100 000 person-years for people with type 1 diabetes. Development of type 1 diabetes before 10 years of age resulted in a loss of 17·7 life-years (95% CI 14·5-20·4) for women and 14·2 life-years (12·1-18·2) for men. INTERPRETATION Age at onset of type 1 diabetes is an important determinant of survival, as well as all cardiovascular outcomes, with highest excess risk in women. Greater focus on cardioprotection might be warranted in people with early-onset type 1 diabetes. FUNDING Swedish Heart and Lung Foundation.
Araz Rawshani, Naveed Sattar, Stefan Franzén, Aidin Rawshani, Andrew T Hattersley, Ann-Marie Svensson, Björn Eliasson, Soffia Gudbjörnsdottir,
Causes and Prevention, Prevalence
Cardiovascular, Diabetes
Apr
16
Glucagon-Like Peptide 1 Receptor Agonists and the Risk of Incident Diabetic Retinopathy.
Abstract
OBJECTIVE Previous studies suggested that glucagon-like peptide 1 receptor agonists (GLP-1 RAs) may initially worsen and possibly increase the risk of diabetic retinopathy. However, data on this possible association remain limited. Thus, this population-based study aimed to determine whether use of GLP-1 RAs is associated with an increased risk of incident diabetic retinopathy. RESEARCH DESIGN AND METHODS Using the U.K. Clinical Practice Research Datalink (CPRD), we conducted a cohort study among 77,115 patients with type 2 diabetes initiating antidiabetic drugs between January 2007 and September 2015. Adjusted hazard ratios (HRs) and 95% CIs of incident diabetic retinopathy were estimated using time-dependent Cox proportional hazards models, comparing use of GLP-1 RAs with current use of two or more oral antidiabetic drugs. In an ancillary analysis, new users of GLP-1 RAs were compared with new users of insulin. RESULTS During 245,825 person-years of follow-up, 10,763 patients were newly diagnosed with diabetic retinopathy. Compared with current use of two or more oral antidiabetic drugs, use of GLP-1 RAs was not associated with an increased risk of incident diabetic retinopathy overall (HR 1.00, 95% CI 0.85-1.17). Compared with insulin, GLP-1 RAs were associated with a decreased risk of diabetic retinopathy (HR 0.67, 95% CI 0.51-0.90). CONCLUSIONS The associations with diabetic retinopathy varied according to the type of comparator. When compared with use of two or more oral antidiabetic drugs, use of GLP-1 RAs was not associated with an increased risk of incident diabetic retinopathy. The apparent lower risk of diabetic retinopathy associated with GLP-1 RAs compared with insulin may be due to residual confounding.
Antonios Douros, Kristian B Filion, Hui Yin, Oriana Hoi Yu, Mahyar Etminan, Jacob A Udell, Laurent Azoulay,
Treatment / Management
Diabetes
Apr
04
Benefits and Harms of Antihypertensive Treatment in Low-Risk Patients With Mild Hypertension.
Abstract
Importance Evidence to support initiation of pharmacologic treatment in low-risk patients with mild hypertension is inconclusive, with previous trials underpowered to demonstrate benefit. Clinical guidelines across the world are contradictory. Objective To examine whether antihypertensive treatment is associated with a low risk of mortality and cardiovascular disease (CVD) in low-risk patients with mild hypertension. Design, Setting, and Participants In this longitudinal cohort study, data were extracted from the Clinical Practice Research Datalink, from January 1, 1998, through September 30, 2015, for patients aged 18 to 74 years who had mild hypertension (untreated blood pressure of 140/90-159/99 mm Hg) and no previous treatment. Anyone with a history of CVD or CVD risk factors was excluded. Patients exited the cohort if follow-up records became unavailable or they experienced an outcome of interest. Exposures Prescription of antihypertensive medication. Propensity scores for likelihood of treatment were constructed using a logistic regression model. Individuals treated within 12 months of diagnosis were matched to untreated patients by propensity score using the nearest-neighbor method. Main Outcomes and Measures The rates of mortality, CVD, and adverse events among patients prescribed antihypertensive treatment at baseline, compared with those who were not prescribed such treatment, using Cox proportional hazards regression. Results A total of 19 143 treated patients (mean [SD] age, 54.7 [11.8] years; 10 705 [55.9%] women; 10 629 [55.5%] white) were matched to 19 143 similar untreated patients (mean [SD] age, 54.9 [12.2] years; 10 631 [55.5%] female; 10 654 [55.7%] white). During a median follow-up period of 5.8 years (interquartile range, 2.6-9.0 years), no evidence of an association was found between antihypertensive treatment and mortality (hazard ratio [HR], 1.02; 95% CI, 0.88-1.17) or between antihypertensive treatment and CVD (HR, 1.09; 95% CI, 0.95-1.25). Treatment was associated with an increased risk of adverse events, including hypotension (HR, 1.69; 95% CI, 1.30-2.20; number needed to harm at 10 years [NNH10], 41), syncope (HR, 1.28; 95% CI, 1.10-1.50; NNH10, 35), electrolyte abnormalities (HR, 1.72; 95% CI, 1.12-2.65; NNH10, 111), and acute kidney injury (HR, 1.37; 95% CI, 1.00-1.88; NNH10, 91). Conclusions and Relevance This prespecified analysis found no evidence to support guideline recommendations that encourage initiation of treatment in patients with low-risk mild hypertension. There was evidence of an increased risk of adverse events, which suggests that physicians should exercise caution when following guidelines that generalize findings from trials conducted in high-risk individuals to those at lower risk.
James P Sheppard, Sarah Stevens, Richard Stevens, Una Martin, Jonathan Mant, F D Richard Hobbs, Richard J McManus,
Treatment / Management
Cardiovascular
Apr
04
Sodium-glucose co-transporter-2 inhibitor use and risk of lower-extremity amputation: Evolving questions, evolving answers
Abstract
AIM To examine whether sodium-glucose co-transporter-2 (SGLT2) inhibitors are associated with a higher risk of lower-extremity amputation than dipeptidyl-peptidase-4 (DPP-4) inhibitors and sulphonylureas. METHODS We conducted a retrospective cohort study, using the MarketScan Commercial Claims and Encounters Database (2013-2015), to compare the incidence of lower-extremity amputation (LEA) between initiators of SGLT2 inhibitors and initiators of two second-line drugs, DPP-4 inhibitors and sulphonylureas (SUs). We estimated crude incidence rates (IRs) and adjusted hazard ratios (aHR), with 95% confidence intervals (CIs), before and after propensity-score weighting. We additionally conducted sensitivity analyses using a comparator group of all non-metformin, non-SGLT2 inhibitor glucose-lowering drugs, as previous studies used this approach. RESULTS In a cohort of 328 150 individuals aged 18 to 64 years, the IR of LEA ranged from 1.5 to 2.4 per 1000 person-years. In as-treated analysis, the estimated hazard of LEA was increased among SGLT2 inhibitor initiators compared to DPP-4 inhibitor initiators (aHR 1.69, 95% CI 1.20-2.38), but not compared to SU initiators (aHR 1.02, 95% CI 0.67-1.55) or non-metformin, non-SGLT2 inhibitor initiators (aHR 1.02, 95% CI 0.54-1.93). Results were consistent in intention-to-treat analysis and across a number of sensitivity analyses. CONCLUSIONS Among commercially insured patients in the United States, our results suggest that initiation of SGLT2 inhibitors may increase the risk of LEA compared to initiation of DPP-4 inhibitors. Contrasting results when comparing SGLT2 inhibitor initiators to DPP-4 inhibitor and SU initiators highlight the importance of choosing appropriate comparator drugs when addressing comparative effectiveness and safety questions that can inform clinical decision-making.
Jeff Y Yang, Tiansheng Wang, Virginia Pate, Emily W Gower, Matthew J Crowley, John B Buse, Til Stürmer,
Treatment / Management
Diabetes
Apr
04
Cumulative Risk of End-Stage Renal Disease Among Patients With Type 2 Diabetes: A Nationwide Inception Cohort Study.
Abstract
OBJECTIVE To estimate long-term cumulative risk of end-stage renal disease (ESRD) after diagnosis of type 2 diabetes. RESEARCH DESIGN AND METHODS This nationwide population-based inception cohort study included 421,429 patients with type 2 diabetes diagnosed in 1990-2011; patients were followed until the end of 2013. Data linkage between several national health care registers in Finland, covering 100% of the population, enabled the inclusion of almost all inhabitants who started taking diabetes medication or were hospitalized for diabetes. Cumulative risk of ESRD and hazard ratios [HR] for ESRD and death were estimated according to age, sex, and time period of diabetes diagnosis. RESULTS Among 421,429 patients with type 2 diabetes, 1,516 developed ESRD and 150,524 died during 3,458,797 patient-years of follow-up. Cumulative risk of ESRD was 0.29% at 10 years and 0.74% at 20 years from diagnosis of diabetes. Risk was higher among men than among women (HR 1.93 [95% CI 1.72-2.16]), decreased with older age at diagnosis (HR 0.70 [95% CI 0.60-0.81] for age 60-69 vs. 40-49 years), and was lower for those diagnosed in 2000-2011 than in 1990-1994 (HR 0.72 [95% CI 0.63-0.81]). Patients diagnosed with diabetes in 2000-2011 had lower risk of death during follow-up than those diagnosed in 1990-1994 (HR 0.64 [95% CI 0.63-0.65]). CONCLUSIONS Cumulative risk of ESRD is minimal among patients with type 2 diabetes compared with their risk of death. Patients diagnosed with diabetes at an older age have a lower risk of ESRD due to higher competing mortality.
Patrik Finne, Per-Henrik Groop, Martti Arffman, Marjo Kervinen, Jaakko Helve, Carola Grönhagen-Riska, Reijo Sund,
Diagnosis; Prognosis
Diabetes, Kidney disease
Apr
04
Inverse Association Between HDL (High-Density Lipoprotein) Cholesterol and Stroke Risk Among Patients With Type 2 Diabetes Mellitus.
Abstract
Background and Purpose- Few studies have assessed the association of HDL (high-density lipoprotein) cholesterol with stroke risk among patients with type 2 diabetes mellitus. We aimed to investigate the association of HDL cholesterol with total and type-specific stroke risk in patients with type 2 diabetes mellitus. Methods- We performed a retrospective cohort study of 27 113 blacks and 40 431 whites with type 2 diabetes mellitus. Cox proportional hazards regression models were used to estimate the association of different levels of HDL cholesterol with stroke risk. Results- During a mean follow-up period of 3.0 years, 8496 patients developed stroke (8048 ischemic and 448 hemorrhagic). Multivariable-adjusted hazard ratios across levels of HDL at baseline (<30 [reference group], 30-39.9, 40-49.9, 50-59.9, 60-69.9, 70-79.9, and ≥80 mg/dL) were 1.00, 0.86, 0.77, 0.71, 0.71, 0.77, and 0.69 ( P <0.001) for total stroke, 1.00, 0.89, 0.82, 0.75, 0.78, 0.76, and 0.75 ( P <0.001) for ischemic stroke, and 1.00, 0.89, 0.69, 0.66, 0.47, and 0.94 ( P =0.021) for hemorrhagic stroke, respectively. When we used an updated mean value of HDL cholesterol, the inverse association of HDL cholesterol with stroke risk did not change. This inverse association was consistent among patients of different ages, races, sexes, body mass index, hemoglobin A1c levels, never and past or current smokers, and patients with and without using glucose-lowering, cholesterol-lowering, or antihypertensive agents. Conclusions- The present study found consistent inverse associations between HDL cholesterol and the risk of total, ischemic and hemorrhagic stroke among patients with type 2 diabetes mellitus.
Yun Shen, Lizheng Shi, Elizabeth Nauman, Peter T Katzmarzyk, Eboni G Price-Haywood, Alessandra N Bazzano, Somesh Nigam, Gang Hu,
Causes and Prevention
Diabetes
Mar
21
Burden and causes for hospitalizations following coronary artery bypass grafting: a nationwide cohort study.
Abstract
OBJECTIVES Hospitalizations are a major burden for both patients and society and are potentially preventable. However, data on the burden and causes for hospitalizations after coronary artery bypass grafting (CABG) are sparse. We examined hospitalizations within 1 year after CABG and associated factors. METHODS Using the Danish nationwide registries, we identified 36 475 patients who underwent first-time isolated CABG (1998-2014) and were discharged alive. Subsequent hospitalizations were classified as cardiovascular or non-cardiovascular according to discharge diagnosis codes. Factors associated with any hospitalization were identified using the Cox regression. RESULTS Thirty-day hospitalization risks for all-cause, cardiovascular and non-cardiovascular reasons were 16.7%, 12.4% and 4.2%, respectively. The corresponding 1-year hospitalization risks were 40.2%, 28.6% and 11.5%. Among patients who survived the first year, 7877 (22.1%) patients were admitted once, 3198 (9.0%) patients were admitted twice and 2844 (8.0%) patients were admitted 3 or more times within the first year. Ischaemic heart disease (15.6%), angina pectoris (9.8%), atrial fibrillation (AF) (8.7%) and heart failure (8.0%) were the most frequent reasons for hospitalization. Factors associated with any hospitalization were lower income level, a history of stroke, heart failure, AF, diabetes, malignancy, chronic renal failure, chronic obstructive pulmonary disease, longer length of stay, postoperative AF and stroke. CONCLUSIONS Within 1-year post-CABG, 40% of patients had at least 1 hospitalization, and approximately 70% of all hospitalizations were attributed to a cardiovascular cause. Lower socioeconomic status, preoperative comorbidities, postoperative complications during index admission and a longer length of stay were associated with hospitalization.
Jawad H Butt, Peter Skov Olsen, Christian Torp-Pedersen, Gunnar H Gislason, Lars Køber, Emil L Fosbøl,
Causes and Prevention
Cardiovascular
Mar
21
Burden and causes for hospitalizations following coronary artery bypass grafting: a nationwide cohort study.
Abstract
OBJECTIVES Hospitalizations are a major burden for both patients and society and are potentially preventable. However, data on the burden and causes for hospitalizations after coronary artery bypass grafting (CABG) are sparse. We examined hospitalizations within 1 year after CABG and associated factors. METHODS Using the Danish nationwide registries, we identified 36 475 patients who underwent first-time isolated CABG (1998-2014) and were discharged alive. Subsequent hospitalizations were classified as cardiovascular or non-cardiovascular according to discharge diagnosis codes. Factors associated with any hospitalization were identified using the Cox regression. RESULTS Thirty-day hospitalization risks for all-cause, cardiovascular and non-cardiovascular reasons were 16.7%, 12.4% and 4.2%, respectively. The corresponding 1-year hospitalization risks were 40.2%, 28.6% and 11.5%. Among patients who survived the first year, 7877 (22.1%) patients were admitted once, 3198 (9.0%) patients were admitted twice and 2844 (8.0%) patients were admitted 3 or more times within the first year. Ischaemic heart disease (15.6%), angina pectoris (9.8%), atrial fibrillation (AF) (8.7%) and heart failure (8.0%) were the most frequent reasons for hospitalization. Factors associated with any hospitalization were lower income level, a history of stroke, heart failure, AF, diabetes, malignancy, chronic renal failure, chronic obstructive pulmonary disease, longer length of stay, postoperative AF and stroke. CONCLUSIONS Within 1-year post-CABG, 40% of patients had at least 1 hospitalization, and approximately 70% of all hospitalizations were attributed to a cardiovascular cause. Lower socioeconomic status, preoperative comorbidities, postoperative complications during index admission and a longer length of stay were associated with hospitalization.
Jawad H Butt, Peter Skov Olsen, Christian Torp-Pedersen, Gunnar H Gislason, Lars Køber, Emil L Fosbøl,
Causes and Prevention
Cardiovascular
Mar
19
β-blockers, calcium antagonists, and mortality in stable coronary artery disease: an international cohort study.
Abstract
Aims The effect of first-line antianginal agents, β-blockers, and calcium antagonists on clinical outcomes in stable coronary artery disease (CAD) remains uncertain. Methods and results We analysed the use of β-blockers or calcium antagonists (baseline and annually) and outcomes in 22 006 stable CAD patients (enrolled 2009-2010) followed annually to 5 years, in the CLARIFY registry (45 countries). Primary outcome was all-cause death. Secondary outcomes were cardiovascular death and the composite of cardiovascular death/non-fatal myocardial infarction (MI). After multivariable adjustment, baseline β-blocker use was not associated with lower all-cause death [1345 (7.8%) in users vs. 407 (8.4%) in non-users; hazard ratio (HR) 0.94, 95% confidence interval (CI) 0.84-1.06; P = 0.30]; cardiovascular death [861 (5.0%) vs. 262 (5.4%); HR 0.91, 95% CI 0.79-1.05; P = 0.20]; or cardiovascular death/non-fatal MI [1272 (7.4%) vs. 340 (7.0%); HR 1.03, 95% CI 0.91-1.16; P = 0.66]. Sensitivity analyses according to β-blocker use over time and to prescribed dose produced similar results. Among prior MI patients, for those enrolled in the year following MI, baseline β-blocker use was associated with lower all-cause death [205 (7.0%) vs. 59 (10.3%); HR 0.68, 95% CI 0.50-0.91; P = 0.01]; cardiovascular death [132 (4.5%) vs. 49 (8.5%); HR 0.52, 95% CI 0.37-0.73; P = 0.0001]; and cardiovascular death/non-fatal MI [212 (7.2%) vs. 59 (10.3%); HR 0.69, 95% CI 0.52-0.93; P = 0.01]. Calcium antagonists were not associated with any difference in mortality. Conclusion In this contemporary cohort of stable CAD, β-blocker use was associated with lower 5-year mortality only in patients enrolled in the year following MI. Use of calcium antagonists was not associated with superior mortality, regardless of history of MI.
Emmanuel Sorbets, Philippe Gabriel Steg, Robin Young, Nicolas Danchin, Nicola Greenlaw, Ian Ford, Michal Tendera, Roberto Ferrari, Bela Merkely, Alexander Parkhomenko, Christopher Reid, Jean-Claude Tardif, Kim M Fox,
Treatment / Management
Cardiovascular
Mar
05
Use of liraglutide and risk of major cardiovascular events: a register-based cohort study in Denmark and Sweden.
Abstract
BACKGROUND Trial evidence shows that the glucagon-like peptide-1 receptor agonist liraglutide significantly reduces the risk of major cardiovascular events among patients with type 2 diabetes who have established cardiovascular disease or are at high cardiovascular risk. We aimed to assess the cardiovascular effectiveness of liraglutide in routine clinical practice. METHODS We used data from nationwide registers in Denmark and Sweden for the period from Jan 1, 2010, to Dec 31, 2016, to investigate the risk of major cardiovascular events associated with use of liraglutide, compared with an active comparator drug class, dipeptidyl peptidase-4 (DPP-4) inhibitors, in patients with type 2 diabetes. The cohort included incident users of liraglutide or DPP-4 inhibitors, who were also using metformin at baseline, matched 1:1 on age, sex, and propensity score. The main outcome was major cardiovascular events, a composite outcome consisting of myocardial infarction, stroke, and cardiovascular death. Other outcomes assessed were the individual components of the main composite outcome, heart failure, death from any cause, and an expanded composite major cardiovascular events outcome that also included other ischaemic heart disease, coronary revascularisation, and peripheral arterial disease. FINDINGS The study population consisted of 23 402 users of liraglutide and 23 402 matched users of DPP-4 inhibitors; patients were followed up for a mean of 3·3 years (SD 2·0). A major cardiovascular event occurred in 1132 users of liraglutide (incidence rate 14·0 per 1000 person-years) and in 1141 users of DPP-4 inhibitors (15·4 per 1000 person-years; hazard ratio [HR] 0·90, 95% CI 0·83-0·98). The HRs were 0·81 (0·71-0·92) for patients with a history of major cardiovascular disease and 0·96 (0·86-1·06) for patients without such a history (p=0·057 [test of homogeneity], suggesting no statistical evidence of heterogeneity). Compared with use of DPP-4 inhibitors, use of liraglutide was associated with a significantly lower risk of cardiovascular death (HR 0·78, 95% CI 0·68-0·91), but no significant differences were identified for risk of myocardial infarction (0·94, 0·84-1·06) or stroke (0·88, 0·77-1·01). Furthermore, use of liraglutide was associated with a significantly lower risk of death from any cause (HR 0·83, 95% CI 0·77-0·90), but no significant differences were identified for risk of heart failure (0·90, 0·80-1·03) or for the expanded major cardiovascular events outcome (0·95, 0·89-1·01). INTERPRETATION In this large Scandinavian cohort, use of liraglutide, as compared with use of DPP-4 inhibitors, was associated with significantly reduced risk of major cardiovascular events. Patients with history of cardiovascular disease seemed to derive the largest benefit from treatment with liraglutide. These data provide support for the cardiovascular effectiveness of liraglutide in routine clinical practice. FUNDING Swedish Heart-Lung Foundation, Novo Nordisk Foundation, and Swedish Society for Medical Research.
Henrik Svanström, Peter Ueda, Mads Melbye, Björn Eliasson, Ann-Marie Svensson, Stefan Franzén, Soffia Gudbjörnsdottir, Kristian Hveem, Christian Jonasson, Björn Pasternak,
Treatment / Management
Cardiovascular, Diabetes
Feb
26
Association between gestational diabetes mellitus and depression in parents: a retrospective cohort study.
Abstract
Purpose The aim of this study was to examine the association between gestational diabetes mellitus (GDM) and depression incidence in mothers and fathers during prenatal and postnatal periods. Patients and methods Matched pairs (GDM vs no GDM) of randomly selected mothers with singleton live births (matched by age group, delivery year, and health region) and their partners (Quebec, Canada; cohort inception 1990-2007) were assessed for a composite outcome of depression/self-harm/suicide using a health administrative database. We examined the association of GDM and the composite outcome in the following three nonoverlapping periods: 1) 24 weeks gestation up to delivery; 2) delivery up to 1 year postpartum; and 3) 1 year postpartum to study end (March 31, 2012). We used stratified Cox proportional regression hazards models, with three models in mothers and three models in fathers, corresponding to each of the time periods of interest. Results In the 58,400 mothers, women with GDM had a nearly twofold greater risk (adjusted HR: 1.82, 95% CI 1.28, 2.59) of being diagnosed with depression compared to those without GDM during the prenatal period. In the first year postpartum, there was no conclusive difference observed between the two groups of mothers (adjusted HR: 1.05, 95% CI 0.84, 1.30). Beyond the first year postpartum, there was an 8% increased risk (adjusted HR: 1.08, 95% CI 1.03, 1.14) of depression in women with a history GDM compared to those without. A total of 63,384 fathers were included in our analyses, and no association between GDM in one's partner and depression was found during any of the three time periods evaluated. Conclusion GDM is associated with an increased risk of depression in women particularly during pregnancy highlighting the need to screen for depression and provide supportive interventions during this period.
Romina Pace, Elham Rahme, Deborah Da Costa, Kaberi Dasgupta,
Diagnosis; Prognosis
Diabetes
Feb
25
Association of metabolic syndrome and chronic kidney disease with atrial fibrillation: A nationwide population-based study in Korea.
Abstract
AIMS Metabolic syndrome (MetS) and chronic kidney disease (CKD) are significant risk factors for incident atrial fibrillation (AF). Few studies have reported the synergistic effect of MetS and CKD on development of AF. We investigated the individual and synergistic effects of MetS and CKD on the risk of incident AF. METHODS We studied a retrospective cohort comprising 22,886,663 Koreans whose data was obtained from the national health claims database established by the Korean National Health Insurance Service between 2008 and 2013. Patients were classified into a MetS and a CKD group and followed-up until 2016 for new-onset AF. A Cox proportional hazards model assessed the independent and synergistic effect of MetS and CKD on the risk of incident AF. RESULTS The prevalence of MetS and CKD in these patients was 27.4% and 5.4%, respectively. During a mean follow-up of 5.4 years, AF developed in 225,529 patients (1% of the total cohort). The adjusted hazard ratio (HR) for incident AF was 1.38 (95% confidence interval [CI] 1.36-1.39) for MetS, and 1.35 (95% CI 1.34-1.37) for CKD. Patients with MetS and CKD showed a higher risk of AF (HR 1.75, 95% CI 1.73-1.78) than that observed in those without MetS and CKD. CONCLUSIONS The combination of MetS and CKD showed a high risk of development of AF in a large-scale nationwide cohort. Further studies are warranted to determine whether pharmacological and/or lifestyle interventions can control/manage these modifiable risk factors to reduce the risk of development of AF.
Won-Seok Choe, Eue-Keun Choi, Kyung-Do Han, Eui-Jae Lee, So-Ryoung Lee, Myung-Jin Cha, Seil Oh,
Diagnosis; Prognosis
Cardiovascular, Kidney disease
Feb
04
Acute Kidney Injury in Patients Receiving Systemic Treatment for Cancer: A Population-Based Cohort Study.
Abstract
Background Patients undergoing treatment for cancer are at increased risk of acute kidney injury (AKI). There are few data on AKI incidence and risk factors in the current era of cancer treatment. Methods We conducted a population-based study of all patients initiating systemic therapy (chemotherapy or targeted agents) for a new cancer diagnosis in Ontario, Canada (2007-2014). The primary outcome was hospitalization with AKI or acute dialysis. We estimated the cumulative incidence of AKI and fitted Fine and Gray models, adjusting for demographics, cancer characteristics, comorbidities, and coprescriptions. We modeled exposure to systemic therapy (the 90-day period following treatments) as a time-varying covariate. We also assessed temporal trends in annual AKI incidence. Results We identified 163 071 patients initiating systemic therapy of whom 10 880 experienced AKI. The rate of AKI was 27 per 1000 person-years, with overall cumulative incidence of 9.3% (95% CI = 9.1% to 9.6%). Malignancies with the highest 5-year AKI incidence were myeloma (26.0%, 95% CI = 24.4% to 27.7%), bladder (19.0%, 95% CI = 17.6% to 20.5%), and leukemia (15.4%, 95% CI = 14.3% to 16.5%). Advanced cancer stage, chronic kidney disease, and diabetes were associated with increased risk of AKI (adjusted hazard ratios [aHR] = 1.41, 95% CI = 1.28 to 1.54; 1.80, 95% CI = 1.67 to 1.93; and 1.43, 95% CI = 1.37 to 1.50, respectively). In patients aged 66 years or older with universal drug benefits, diuretic, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker coprescription was associated with higher AKI risk (aHR = 1.20, 95% CI = 1.14 to 1.28; 1.30, 95% CI = 1.23 to 1.38). AKI risk was further accentuated during the 90-day period following systemic therapy (aHR = 2.34, 95% CI = 2.24 to 2.45). The annual incidence of AKI increased from 18 to 52 per 1000 person-years between 2007 and 2014. Conclusion Cancer-related AKI is common and associated with advanced stage, chronic kidney disease, diabetes, and concomitant receipt of diuretics or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. Risk is heightened in the 90 days after systemic therapy. Preventive strategies are needed to address the increasing burden of AKI in this population.
Abhijat Kitchlu, Eric McArthur, Eitan Amir, Christopher M Booth, Rinku Sutradhar, Habeeb Majeed, Danielle M Nash, Samuel A Silver, Amit X Garg, Christopher T Chan, S Joseph Kim, Ron Wald,
Causes and Prevention
Kidney disease
Jan
28
Time to Treatment Intensification After Monotherapy Failure and Its Association With Subsequent Glycemic Control Among 93,515 Patients With Type 2 Diabetes.
Abstract
OBJECTIVE The goal of this study was to evaluate the association between the timing of treatment intensification and subsequent glycemic control among patients with type 2 diabetes in whom monotherapy fails. RESEARCH DESIGN AND METHODS This retrospective analysis of the U.K. Clinical Practice Research Datalink database focused on patients with type 2 diabetes and one or more HbA measurements ≥7% (≥53 mmol/mol) after ≥3 months of metformin or sulfonylurea monotherapy (first measurement meeting these criteria was taken as the study index date). Baseline (6 months before the index date) characteristics were stratified by time from the index date to intensification (early: <12 months; intermediate: 12 to <24 months; late: 24 to <36 months). Intensification was defined as initiating after the index date one or more noninsulin antidiabetes medication in addition to metformin or a sulfonylurea. Association between time to intensification and subsequent glycemic control (first HbA <7% [<53 mmol/mol] after intensification) was evaluated using Kaplan-Meier analyses and Cox proportional hazard models that accounted for baseline differences. RESULTS Of the 93,515 patients who met the study criteria (mean age 60 years; ∼59% male; 80% taking metformin), 23,761 (25%) intensified <12 months after the index date; 11,908 (13%) intensified after 12 to <24 months; and 7,146 (8%) intensified after 24 to <36 months. Patients who intensified treatment ≥36 months after the index date ( = 9,638 [10%]) and those with no evidence of treatment intensification during the observable follow-up period ( = 41,062 [44%]) were not included in further analyses. The median times from intensification to control were 20.0, 24.1, and 25.7 months, respectively, for the early, intermediate, and late intensification cohorts. After adjustment for baseline differences, the likelihood of attaining glycemic control was 22% and 28% lower for patients in the intermediate and late intensification groups, respectively, compared with those intensifying early ( < 0.0001). CONCLUSIONS Earlier treatment intensification is associated with shorter time to subsequent glycemic control, independent of whether patients initiate first-line treatment with metformin or a sulfonylurea.
Urvi Desai, Noam Y Kirson, Jennifer Kim, Kamlesh Khunti, Sarah King, Erich Trieschman, Michael Hellstern, Phillip R Hunt, Jayanti Mukherjee,
Treatment / Management
Diabetes
Jan
21
Statins for Primary Prevention of Cardiovascular Events and Mortality in Older Men.
Abstract
BACKGROUND/OBJECTIVES We sought to determine whether statin use for primary prevention is associated with a lower risk of cardiovascular events or mortality in older men. DESIGN Prospective cohort study. SETTING Physicians' Health Study participants. PARTICIPANTS 7,213 male physicians ≥70 years without a history of cardiovascular disease (CVD). MEASUREMENTS Multivariable propensity score for statin use with greedy matching (1:1) to minimize confounding by indication. RESULTS Median baseline age was 77 (70-102), median follow-up was 7 years. Non-users were matched to 1,130 statin users. Statin use was associated with an 18% lower risk of all-cause mortality, HR 0.82 (95% CI 0.69-0.98) and non-significant lower risk of CVD events, HR 0.86 (95% CI 0.70-1.06) and stroke, HR 0.70 (95% CI 0.45-1.09). In subgroup analyses, results did not change according to age group at baseline (70-76 or >76 years) or functional status. There was a suggestion that those >76 at baseline did not benefit from statins for mortality, HR 1.14 (95% CI 0.89-1.47), compared to those 70-76 at baseline, HR 0.83 (95% CI 0.61-1.11); however the CIs overlap between the two groups, suggesting no difference. Statin users with elevated total cholesterol had fewer major CVD events than non-users, HR 0.68 (95% CI 0.50-0.94) and HR 1.43 (95% CI 0.99-2.07)), respectively. CONCLUSIONS Statin use was associated with a significant lower risk of mortality in older male physicians ≥70 and a nonsignificant lower risk of CVD events. Results did not change in those who were >76 years at baseline or according to functional status. There was a suggestion that those with elevated total cholesterol may benefit. Further work is needed to determine which older individuals will benefit from statins as primary prevention.
Ariela R Orkaby, J Michael Gaziano, Luc Djousse, Jane A Driver,
Treatment / Management
Cardiovascular
Jan
15
Cardiovascular Benefits of Acarbose vs Sulfonylureas in Patients With Type 2 Diabetes Treated With Metformin.
Abstract
Context Although α-glucosidase inhibitors (AGIs) have been shown to reduce the risk of myocardial infarction in patients with impaired glucose tolerance, the cardiovascular benefits of AGIs in those with type 2 diabetes (T2D) remains unclear. Objective We compared the clinical outcomes of adding acarbose vs sulfonylureas to metformin therapy in patients with T2D. Design, Setting, and Participants The study population was drawn from the database of the Diabetes Pay-for-Performance program in Taiwan. Sulfonylureas and acarbose were prescribed to 196,143 and 14,306 patients with T2D, respectively, from 2004 to 2015, who had been treated with metformin. A propensity score-matched cohort study was conducted. The patients were followed up for clinical adverse events of all-cause mortality and hospitalizations of major atherosclerotic events (i.e., myocardial infarction and ischemic stroke), heart failure, or hypoglycemia. Results A total of 14,306 propensity score-matched pairs (age, 55.8 ± 13.1 years; 47.8% men) were enrolled in the present analysis. Compared with sulfonylureas as the add-on therapy to metformin, the use of acarbose was associated with significantly lower risks of hospitalizations for major atherosclerotic events [hazard ratio (HR), 0.69; 95% CI, 0.52 to 0.91], ischemic stroke (HR, 0.68; 95% CI, 0.49 to 0.94), and hypoglycemia (HR, 0.23; 95% CI, 0.08 to 0.71), after accounting for major confounding factors. Conclusions In T2D treatment, the use of acarbose as an add-on remedy to metformin was associated with lower risks of major atherosclerotic events, ischemic stroke, and hypoglycemia compared with the use of sulfonylurea as an add-on remedy.
Pai-Feng Hsu, Shih-Hsien Sung, Hao-Min Cheng, Shyi-Jang Shin, Kun-Der Lin, Keong Chong, Fu-Shun Yen, Ben-Hui Yu, Chi-Ting Huang, Chih-Cheng Hsu,
Treatment / Management
Cardiovascular, Diabetes
Dec
04
Sulfonylureas as second line drugs in type 2 diabetes and the risk of cardiovascular and hypoglycaemic events: population based cohort study.
Abstract
OBJECTIVE To assess whether adding or switching to sulfonylureas is associated with an increased risk of myocardial infarction, ischaemic stroke, cardiovascular death, all cause mortality, and severe hypoglycaemia, compared with remaining on metformin monotherapy in patients with type 2 diabetes. DESIGN Population based cohort study. SETTING General practices contributing data to the UK Clinical Practice Research Datalink. PARTICIPANTS Patients with type 2 diabetes initiating metformin monotherapy between 1998 and 2013. MAIN OUTCOME MEASURES Using the prevalent new-user cohort design we matched 1:1 patients adding or switching to sulfonylureas with those remaining on metformin monotherapy on high-dimensional propensity score, haemoglobin A1c, and number of previous metformin prescriptions. The two groups were compared using Cox proportional hazards models to estimate adjusted hazard ratios and 95% confidence intervals for the study outcomes. RESULTS Among 77 138 metformin initiators, 25 699 added or switched to sulfonylureas during the study period. During a mean follow-up of 1.1 years, sulfonylureas were associated with an increased risk of myocardial infarction (incidence rate 7.8 6.2 per 1000 person years, hazard ratio 1.26, 95% confidence interval 1.01 to 1.56), all cause mortality (27.3 21.5, 1.28, 1.15 to 1.44), and severe hypoglycaemia (5.5 0.7, 7.60, 4.64 to 12.44) compared with continuing metformin monotherapy. There was a trend towards increased risks of ischaemic stroke (6.7 5.5, 1.24, 0.99 to 1.56) and cardiovascular death (9.4 8.1, 1.18, 0.98 to 1.43). Compared with adding sulfonylureas, switching to sulfonylureas was associated with an increased risk of myocardial infarction (hazard ratio 1.51, 95% confidence interval, 1.03 to 2.24) and all-cause mortality (1.23, 1.00 to 1.50). No differences were observed for ischaemic stroke, cardiovascular death, or severe hypoglycaemia. CONCLUSIONS Sulfonylureas as second line drugs are associated with an increased risk of myocardial infarction, all cause mortality, and severe hypoglycaemia, compared with remaining on metformin monotherapy. Continuing metformin when introducing sulfonylureas appears to be safer than switching.
Antonios Douros, Sophie Dell'Aniello, Oriana Hoi Yun Yu, Kristian B Filion, Laurent Azoulay, Samy Suissa,
Treatment / Management
Cardiovascular, Diabetes
Dec
04
Association Between Sodium-Glucose Cotransporter 2 Inhibitors and Lower Extremity Amputation Among Patients With Type 2 Diabetes.
Abstract
Importance Results of clinical trials suggest that canagliflozin, a sodium-glucose cotransporter 2 (SGLT-2) inhibitor for treating type 2 diabetes, may be associated with lower extremity amputation. Objective To quantify the association between the use of oral medication for type 2 diabetes and 5 outcomes (lower extremity amputation, peripheral arterial disease, critical limb ischemia, osteomyelitis, and ulcer). Design, Setting, and Participants A retrospective cohort study was conducted using Truven Health MarketScan Commercial Claims and Encounters data on new users between September 1, 2012, and September 30, 2015. The study focused on 2.0 million commercially insured individuals and used propensity score weighting to balance baseline differences among groups. Sensitivity analyses varied statistical models, assessed the effect of combining dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide 1 (GLP-1) agonists as a single referent group, adjusted for baseline use of older oral agents, and included people with baseline amputation. Exposures New use of SGLT-2 inhibitors alone, DPP-4 inhibitors alone, GLP-1 agonists alone, or other antidiabetic agents (sulfonylurea, metformin hydrochloride, or thiazolidinediones). Main Outcomes and Measures Foot and leg amputation, defined by validated International Classification of Diseases, Ninth Revision and Current Procedural Terminology codes. Results Among 2.0 million potentially eligible individuals, a total of 953 906 (516 046 women and 437 860 men; mean [SD] age, 51.8 [10.9] years) were included in the final analyses, including 39 869 new users of SGLT-2 inhibitors (4.2%), 105 023 new users of DPP-4 inhibitors (11.0%), and 39 120 new users of GLP-1 agonists (4.1%). The median observation time ranged from 99 days for new users of GLP-1 agonists to 127 days for those using metformin, sulfonylureas, and thiazolidinediones, while the crude incident rates ranged from 4.90 per 10 000 person-years for those using metformin, sulfonylureas, and thiazolidinediones to 10.53 per 10 000 person-years for new users of SGLT-2 inhibitors. After propensity score weighting and adjustment for demographics, severity of diabetes, comorbidities, and medications, there was a nonstatistically significant increased risk of amputation associated with new use of SGLT-2 inhibitors compared with DPP-4 inhibitors (adjusted hazard ratio, 1.50; 95% CI, 0.85-2.67) and GLP-1 agonists (adjusted hazard ratio, 1.47; 95% CI, 0.64-3.36). New use of SGLT-2 inhibitors was statistically significantly associated with amputation compared with sulfonylureas, metformin, or thiazolidinediones (adjusted hazard ratio, 2.12; 95% CI, 1.19-3.77). These results persisted in sensitivity analyses. Conclusions and Relevance Use of SGLT-2 inhibitors may be associated with increased risk of amputation compared with some oral treatments for type 2 diabetes. Further observational studies are needed with extended follow-up and larger sample sizes.
Hsien-Yen Chang, Sonal Singh, Omar Mansour, Sheriza Baksh, G Caleb Alexander,
Treatment / Management
Cardiovascular, Diabetes
Dec
03
Effects on clinical outcomes of intensifying triple oral antidiabetic drug (OAD) therapy by initiating insulin versus enhancing OAD therapy in patients with type 2 diabetes: A nationwide population-based, propensity-score-matched cohort study.
Abstract
AIMS To compare the effects of initiating insulin as a fourth-line antidiabetic therapy with the effects of enhancing oral antidiabetic drug (OAD) therapy in patients with type 2 diabetes mellitus (T2DM) with triple OAD therapy failure. MATERIALS AND METHODS We conducted a nationwide population-based, retrospective cohort study involving 1022 (without prevalent diabetes-related complications [PDRCs]) and 2077 (with/without PDRCs) propensity score-matched pairs of fourth-line insulin therapy users and enhanced OAD therapy users identified in the period 2004 to 2010. Clinical outcomes including a composite cardiovascular outcome (myocardial infarction, stroke, heart failure or ischaemic heart disease), peripheral vascular disease (PVD), hypoglycaemia and all-cause mortality were assessed up to 2013. Hypoglycaemia was adjusted in Cox models to consider its potential effect on study outcomes. RESULTS In a T2DM cohort without PDRCs, fourth-line insulin therapy was not associated with greater risks of clinical outcomes, except hypoglycaemia (hazard ratio [HR] 1.45, 95% confidence interval [CI] 1.02-2.07), compared with enhanced OAD therapy. Among patients with T2DM with/without PDRCs, fourth-line insulin therapy was associated with greater risks of the composite cardiovascular outcome (HR 1.23, 95% CI 1.03-1.46), heart failure (HR 1.59, 95% CI 1.12-2.25), ischaemic heart disease (HR 1.37, 95% CI 1.09-1.73), PVD (HR 1.17, 95% CI 1.00-1.36), hypoglycaemia (HR 1.49, 95% CI 1.20-1.85) and all-cause mortality (HR 1.48, 95% CI 1.01-2.17), but adjustment for hypoglycaemia significantly attenuated the risk of heart failure (HR 1.34, 95% CI 0.92-1.94), PVD (HR 1.15, 95% CI 0.98-1.34) and all-cause mortality (HR 1.30, 95% CI 0.84-1.99). CONCLUSIONS Initiation of fourth-line insulin therapy can be considered for patients with T2DM with triple OAD therapy failure, and the importance of awareness and prevention of hypoglycaemia among insulin-treated patients with T2DM cannot be overstated.
Shihchen Kuo, Chun-Ting Yang, Jin-Shang Wu, Huang-Tz Ou,
Treatment / Management
Cardiovascular, Diabetes
Nov
22
Association of BMI with overall and cause-specific mortality: a population-based cohort study of 3·6 million adults in the UK.
Abstract
BACKGROUND BMI is known to be strongly associated with all-cause mortality, but few studies have been large enough to reliably examine associations between BMI and a comprehensive range of cause-specific mortality outcomes. METHODS In this population-based cohort study, we used UK primary care data from the Clinical Practice Research Datalink (CPRD) linked to national mortality registration data and fitted adjusted Cox regression models to examine associations between BMI and all-cause mortality, and between BMI and a comprehensive range of cause-specific mortality outcomes (recorded by International Classification of Diseases, 10th revision [ICD-10] codes). We included all individuals with BMI data collected at age 16 years and older and with subsequent follow-up time available. Follow-up began at whichever was the latest of: start of CPRD research-standard follow up, the 5-year anniversary of the first BMI record, or on Jan 1, 1998 (start date for death registration data); follow-up ended at death or on March 8, 2016. Fully adjusted models were stratified by sex and adjusted for baseline age, smoking, alcohol use, diabetes, index of multiple deprivation, and calendar period. Models were fitted in both never-smokers only and the full study population. We also did an extensive range of sensitivity analyses. The expected age of death for men and women aged 40 years at baseline, by BMI category, was estimated from a Poisson model including BMI, age, and sex. FINDINGS 3 632 674 people were included in the full study population; the following results are from the analysis of never-smokers, which comprised 1 969 648 people and 188 057 deaths. BMI had a J-shaped association with overall mortality; the estimated hazard ratio per 5 kg/m increase in BMI was 0·81 (95% CI 0·80-0·82) below 25 kg/m and 1·21 (1·20-1·22) above this point. BMI was associated with all cause of death categories except for transport-related accidents, but the shape of the association varied. Most causes, including cancer, cardiovascular diseases, and respiratory diseases, had a J-shaped association with BMI, with lowest risk occurring in the range 21-25 kg/m. For mental and behavioural, neurological, and accidental (non-transport-related) causes, BMI was inversely associated with mortality up to 24-27 kg/m, with little association at higher BMIs; for deaths from self-harm or interpersonal violence, an inverse linear association was observed. Associations between BMI and mortality were stronger at younger ages than at older ages, and the BMI associated with lowest mortality risk was higher in older individuals than in younger individuals. Compared with individuals of healthy weight (BMI 18·5-24·9 kg/m), life expectancy from age 40 years was 4·2 years shorter in obese (BMI ≥30·0 kg/m) men and 3·5 years shorter in obese women, and 4·3 years shorter in underweight (BMI <18·5 kg/m) men and 4·5 years shorter in underweight women. When smokers were included in analyses, results for most causes of death were broadly similar, although marginally stronger associations were seen among people with lower BMI, suggesting slight residual confounding by smoking. INTERPRETATION BMI had J-shaped associations with overall mortality and most specific causes of death; for mental and behavioural, neurological, and external causes, lower BMI was associated with increased mortality risk. FUNDING Wellcome Trust.
Krishnan Bhaskaran, Isabel Dos-Santos-Silva, David A Leon, Ian J Douglas, Liam Smeeth,
Causes and Prevention
Cardiovascular, Diabetes
Nov
13
Glycemic Control and Risk of Infections Among People With Type 1 or Type 2 Diabetes in a Large Primary Care Cohort Study.
Abstract
OBJECTIVE Diabetes mellitus (DM) increases the risk of infections, but the effect of better control has not been thoroughly investigated. RESEARCH DESIGN AND METHODS With the use of English primary care data, average glycated hemoglobin (HbA) during 2008-2009 was estimated for 85,312 patients with DM ages 40-89 years. Infection rates during 2010-2015 compiled from primary care, linked hospital, and mortality records were estimated across 18 infection categories and further summarized as any requiring a prescription or hospitalization or as cause of death. Poisson regression was used to estimate adjusted incidence rate ratios (IRRs) by HbA categories across all DM, and type 1 and type 2 DM separately. IRRs also were compared with 153,341 age-sex-practice-matched controls without DM. Attributable fractions (AF%) among patients with DM were estimated for an optimal control scenario (HbA 6-7% [42-53 mmol/mol]). RESULTS Long-term infection risk rose with increasing HbA for most outcomes. Compared with patients without DM, those with DM and optimal control (HbA 6-7% [42-53 mmol/mol], IRR 1.41 [95% CI 1.36-1.47]) and poor control (≥11% [97 mmol/mol], 4.70 [4.24-5.21]) had elevated hospitalization risks for infection. In patients with type 1 DM and poor control, this risk was even greater (IRR 8.47 [5.86-12.24]). Comparisons within patients with DM confirmed the risk of hospitalization with poor control (2.70 [2.43-3.00]) after adjustment for duration and other confounders. AF% of poor control were high for serious infections, particularly bone and joint (46%), endocarditis (26%), tuberculosis (24%), sepsis (21%), infection-related hospitalization (17%), and mortality (16%). CONCLUSIONS Poor glycemic control is powerfully associated with serious infections and should be a high priority.
Julia A Critchley, Iain M Carey, Tess Harris, Stephen DeWilde, Fay J Hosking, Derek G Cook,
Diagnosis; Prognosis
Diabetes
Oct
30
Thiazolidinediones and reduced risk of incident bacterial abscess in adults with type 2 diabetes: A population-based cohort study.
Abstract
AIM Previous research has suggested that peroxisome proliferator-activated receptor-gamma (PPAR-γ) may play an important role in immunomodulation. We aimed to examine the association between thiazolidinediones, PPAR-γ agonists and incidence of bacterial abscess among patients with type 2 diabetes. MATERIALS AND METHODS This retrospective cohort study between 2000 and 2010 included 46 986 propensity (PS)-matched patients diagnosed with type 2 diabetes. We compared the incidence of bacterial abscess, including liver and non-liver abscesses, between patients treated with metformin plus a thiazolidinedione (M + T, N = 7831) or metformin plus a sulfonylurea (M + S, N = 39 155). Data were retrieved from a population-based Taiwanese database. We applied Cox proportional hazard regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), comparing M + T and M + S after PS matching. RESULTS During a median follow-up of 4.5 years, the incidence rate of bacterial abscess was lower with M + T than with M + S treatment (1.89 vs 3.15 per 1000 person-years) in the PS-matched cohort. M + T was associated with a reduced risk of bacterial abscess (HRs after PS matching, 0.58; 95% CI, 0.42-0.80 for total bacterial abscess; 0.54; 95% CI, 0.28-1.07 for liver abscess; 0.59; 95% CI, 0.41-0.85 for non-liver abscess). Results did not change materially after accounting for unmeasured confounding factors using high-dimenional PS matching and differential censoring between regimen groups. Rosiglitazone and pioglitazone, in combination with metformin, produced similar reductions in risk of all abscess outcomes. CONCLUSION We found that M + T may provide a protective benefit in reducing the incidence of bacterial abscesses. These findings merit further investigation.
Jiun-Ling Wang, Yaa-Hui Dong, Wen-Chien Ko, Chia-Hsuin Chang, Li-Chiu Wu, Lee-Ming Chuang, Pau-Chung Chen,
Treatment / Management
Diabetes
Oct
16
Acute Kidney Injury and Risk of Heart Failure and Atherosclerotic Events.
Abstract
BACKGROUND AND OBJECTIVES AKI in the hospital is common and is associated with excess mortality. We examined whether AKI is also independently associated with a higher risk of different cardiovascular events in the first year after discharge. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We conducted a retrospective analysis of a cohort between 2006 and 2013 with follow-up through 2014, within Kaiser Permanente Northern California. We identified all adults admitted to 21 hospitals who had one or more in-hospital serum creatinine test result and survived to discharge. Occurrence of AKI was on the basis of Kidney Disease: Improving Global Outcomes diagnostic criteria. Potential confounders were identified from comprehensive inpatient and outpatient, laboratory, and pharmacy electronic medical records. During the 365 days after discharge, we ascertained occurrence of heart failure, acute coronary syndromes, peripheral artery disease, and ischemic stroke events from electronic medical records. RESULTS Among a matched cohort of 146,941 hospitalized adults, 31,245 experienced AKI. At 365 days postdischarge, AKI was independently associated with higher rates of the composite outcome of hospitalization for heart failure and atherosclerotic events (adjusted hazard ratio [aHR], 1.18; 95% confidence interval [95% CI], 1.13 to 1.25) even after adjustment for demographics, comorbidities, preadmission eGFR and proteinuria, heart failure and sepsis complicating the hospitalization, intensive care unit (ICU) admission, length of stay, and predicted in-hospital mortality. This was driven by an excess risk of subsequent heart failure (aHR, 1.44; 95% CI, 1.33 to 1.56), whereas there was no significant association with follow-up atherosclerotic events (aHR, 1.05; 95% CI, 0.98 to 1.12). CONCLUSIONS AKI is independently associated with a higher risk of cardiovascular events, especially heart failure, after hospital discharge.
Alan S Go, Chi-Yuan Hsu, Jingrong Yang, Thida C Tan, Sijie Zheng, Juan D Ordonez, Kathleen D Liu,
Diagnosis; Prognosis
Cardiovascular, Kidney disease
Oct
09
End Stage Renal Disease Patients Using Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers May Reduce the Risk of Mortality: A Taiwanese Nationwide Cohort Study.
Abstract
BACKGROUND The association between angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) use and mortality in end stage renal disease (ESRD) patients lacks sufficient evidence. We aim to investigate the efficacy of ACEIs and ARBs in ESRD patients. METHODS This nationwide retrospective cohort study using data from the Taiwan National Health Insurance Research Database enrolled ESRD patients from January 1997 to December 2011. Propensity score matching provided two study groups (ACEI/ARB users vs. nonusers) balanced in sample size with similar comorbidities and prescriptions. These patients were followed from the first date of receiving dialysis until mortality, 5 years, or December 31, 2013 (whichever came first). We analyzed the association of the use of ACEIs or ARBs with cardiovascular (CV) death and all-cause mortality in patients with ESRD by using the Kaplan-Meier method and time-dependent Cox models with a robust sandwich variance method. RESULTS After propensity score matching, all characteristics of the user of ACEIs or ARBs (n = 17,280) and nonuser (n = 17,280) groups were appropriately balanced (P > .05). In the Cox proportional hazards model, the user group exhibited lower CV death and all-cause mortality with adjusted hazard ratios (HRs) and 95%CI of 0.58 (0.55-0.62) and 0.47 (0.46-0.49) than the nonuser group did. Furthermore, the association of ACEIs/ARBs use with low mortality risk was observed in all examined subgroups. CONCLUSION In this large-scale, population-based cohort study, ESRD patients using ACEIs/ARBs had a lower risk of CV death and all-cause mortality than nonusers did. This article is protected by copyright. All rights reserved.
Lee, Hsin-Fu See, Lai-Chu Chan, Yi-Hsin Yeh, Yung-Hsin Wu, Lung-Sheng Liu, Jia-Rou Tu, Hui-Tzu Wang, Chun-Li Kuo, Chi-Tai Chang, Shang-Hung
Diagnosis; Prognosis
Kidney disease
Oct
09
Chronic kidney disease and cause-specific hospitalisation: a matched cohort study using primary and secondary care patient data.
Abstract
BACKGROUND Although chronic kidney disease (CKD) is associated with various outcomes, the burden of each condition for hospital admission is unknown. AIM To quantify the association between CKD and cause-specific hospitalisation. DESIGN AND SETTING A matched cohort study in primary care using Clinical Practice Research Datalink linked to Hospital Episode Statistics in England. METHOD Patients with CKD (estimated glomerular filtration rate <60 mL/min/1.73 m for ≥3 months) and a comparison group of patients without known CKD (matched for age, sex, GP, and calendar time) were identified, 2004-2014. Outcomes were hospitalisations with 10 common conditions as the primary admission diagnosis: heart failure; urinary tract infection; pneumonia; acute kidney injury (AKI); myocardial infarction; cerebral infarction; gastrointestinal bleeding; hip fracture; venous thromboembolism; and intracranial bleeding. A difference in the incidence rate of first hospitalisation for each condition was estimated between matched patients with and without CKD. Multivariable Cox regression was used to estimate a relative risk for each outcome. RESULTS In a cohort of 242 349 pairs of patients, with and without CKD, the rate difference was largest for heart failure at 6.6/1000 person-years (9.7/1000 versus 3.1/1000 person-years in patients with and without CKD, respectively), followed by urinary tract infection at 5.2, pneumonia at 4.4, and AKI at 4.1/1000 person-years. The relative risk was highest for AKI with a fully adjusted hazard ratio of 4.90, 95% confidence interval (CI) = 4.47 to 5.38, followed by heart failure with 1.66, 95% CI = 1.59 to 1.75. CONCLUSION Hospitalisations for heart failure, infection, and AKI showed strong associations with CKD in absolute and(or) relative terms, suggesting targets for improved preventive care.
Masao Iwagami, Ben Caplin, Liam Smeeth, Laurie A Tomlinson, Dorothea Nitsch,
Diagnosis; Prognosis
Kidney disease
Oct
09
Effect of medication adherence on long-term all-cause-mortality and hospitalization for cardiovascular disease in 65,067 newly diagnosed type 2 diabetes patients.
Abstract
This study determined the effects of anti-diabetic medication adherence on the long-term all-cause mortality and hospitalization for cerebrovascular disease and myocardial infarction among newly diagnosed patients. The study used retrospective cohort from the National Health Insurance Service. Study participants were 65,076 newly diagnosed type 2 diabetes mellitus patients aged ≥40 years. The medication adherence was evaluated from the proportion of days covered (PDC) between 2006 and 2007. Outcome variables were mortality, newly diagnosed cerebrovascular disease (CVD) and myocardial infarction (MI) in 2008-2017. Cox-proportional hazard regression analysis was performed. After adjusting for sex, age, monthly contribution, insurance type, medical institution type, Charlson comorbidity index score, disability, hypertension, and active ingredients of oral hypoglycemic agents, the adjusted hazard ratio (aHR) for all-cause-mortality of the lowest PDC group (<0.20) was 1.45 (95% confidence interval [CI] = 1.36-1.54) as compared to the highest PDC (≥0.8). The aHR for all-cause-mortality associated with PDC levels of 0.60-0.79, 0.40-0.59, and 0.20-0.39 were 1.19, 1.26, and 1.34, respectively (P < 0.001). Compared to the highest PDC group, diabetic patients with the lowest PDC had elevated risk for CVD (aHR = 1.41; 95% CI = 1.30-1.52; P < 0.001). Improving anti-diabetic medication adherence among newly diagnosed type 2 diabetes mellitus patients is essential to the reduce risk for cardiovascular disease and long-term all-cause mortality.
Yeon-Yong Kim, Jin-Seok Lee, Hee-Jin Kang, Sang Min Park,
Treatment / Management
Cardiovascular, Diabetes
Sep
04
Young-Adult Polycystic Kidney Disease is Associated with Major Cardiovascular Complications.
Abstract
Patients with polycystic kidney disease (PKD) might have a risk of cardiovascular diseases because several cardiovascular risk factors are occasionally associated with PKD patients. Data on the association between PKD and the risk of cardiovascular events, including acute coronary syndrome (ACS), stroke, and congestive heart failure (CHF), are scant. Patients aged &ge;20 years who were newly diagnosed with PKD (International Classification of Diseases, Ninth Revision, Clinical Modification codes 753.12 and 753.13) between 2000 and 2011 were selected as a PKD cohort (N = 5157). The association between PKD and cardiovascular events was analyzed. We randomly selected a comparison cohort of people without PKD, who were frequency-matched by sex, age, and index date of diagnosis. At the end of 2011, the PKD cohort had a 1.40-fold greater incidence of ACS compared with the comparison cohort (8.59 vs. 6.17 per 1000 person-years), in addition to a 1.40-fold greater incidence of stroke, a 1.49-fold greater incidence of CHF, and a 1.64-fold greater incidence of mortality. This retrospective cohort study shows that patients with PKD have an increased risk of cardiovascular events including ACS, stroke, and CHF as well as mortality, particularly in younger patients. Early identification is necessary to attenuate the risk of cardiovascular complications in patients with PKD.
Ya-Wen Chuang, Tung-Min Yu, Shih-Ting Huang, Kuo-Ting Sun, Ying-Chih Lo, Pin-Kuei Fu, Bor-Jen Lee, Cheng-Hsu Chen, Cheng-Li Lin, Chia-Hung Kao,
Diagnosis; Prognosis
Cardiovascular
Aug
09
Increased risk of open-angle glaucoma among patients with diabetes mellitus: a 10-year follow-up nationwide cohort study.
Abstract
PURPOSE To evaluate the risk of open-angle glaucoma among patients with diabetes. METHODS This retrospective propensity score-matched cohort study included patients with diabetes and a matched comparison group from the Korean National Health Insurance Service National Health Screening Cohort, which includes approximately 500 000 adults aged ≥40 years. Nondiabetes group was matched to diabetes group in a 1:1 ratio using a propensity score based on age, sex, comorbidities, antihypertensive medication use and medical care visits. Each group was followed from January 1, 2004 to either the date of developing open-angle glaucoma or the date of last follow-up in 2013. RESULTS Incidence of open-angle glaucoma was 20.0/10 000 person-years in diabetes group (n = 58 358) and 17.0/10 000 person-years in nondiabetes group (n = 58 358). Age- and sex- adjusted hazard ratio (HR) was 1.19 (95% confidence interval [CI], 1.09-1.30). In the subgroup analyses, diabetes was associated with an increased risk of open-angle glaucoma in both younger and older age groups (HR = 1.20 for those aged 40-59 years and HR = 1.18 for those aged 60-79 years) and in both sexes (men, HR = 1.13; women, HR = 1.27). CONCLUSION Patients diagnosed with diabetes were more likely to develop open-angle glaucoma compared with patients without diabetes.
Tyler Hyungtaek Rim, Sang Yeop Lee, Hyoung Won Bae, Gong Je Seong, Sung Soo Kim, Chan Yun Kim,
Diagnosis; Prognosis
Diabetes
Aug
09
Hyperkalaemia in people with diabetes: occurrence, risk factors and outcomes in a Danish population-based cohort study.
Abstract
AIMS To examine the incidence, risk factors and clinical outcomes of hyperkalaemia in people with diabetes in a real-world setting. METHODS Using Danish health registries, we identified a population-based cohort of people with first-time drug-treated diabetes, in the period 2000-2012. First, the cumulative incidence of hyperkalaemia, defined as first blood test with potassium level >5.0 mmol/l after diabetes treatment initiation, was ascertained. Second, in a case-control analysis, risk factors were compared in people with vs without hyperkalaemia. Third, clinical outcomes were assessed among individuals with hyperkalaemia in a before-after analysis, and among people with and without hyperkalaemia in a matched cohort analysis. RESULTS Of 68 601 individuals with diabetes (median age 62 years, 47% women), 16% experienced hyperkalaemia (incidence rate 40 per 1000 person-years) during a mean follow-up of 4.1 years. People who developed hyperkalaemia had a higher prevalence of chronic kidney disease [prevalence ratio 1.74 (95% CI 1.68-1.81)], heart failure [prevalence ratio 2.35 (95% CI 2.18-2.54)], use of angiotensin-converting enzyme inhibitors [prevalence ratio 1.24 (95% CI 1.20-1.28)], use of spironolactone [prevalence ratio 2.68 (95% CI 2.48-2.88)] and potassium supplements [prevalence ratio 1.59 (95% CI 1.52-1.67)]. In people with diabetes who developed hyperkalaemia, 31% were acutely hospitalized within 6 months before hyperkalaemia, increasing to 50% 6 months after hyperkalaemia [before-after risk ratio 1.67 (95% CI 1.61-1.72)]. The 6-month mortality rate after hyperkalaemia was 20%. Compared with matched individuals without hyperkalaemia, the hazard ratio for death was 6.47 (95% CI 5.81-7.21). CONCLUSIONS One in six newly diagnosed people with diabetes experienced a hyperkalaemic event, which was associated with severe clinical outcomes and death.
R W Thomsen, S K Nicolaisen, K Adelborg, E Svensson, P Hasvold, E Palaka, L Pedersen, H T Sørensen,
Diagnosis; Prognosis, Prevalence
Diabetes, Kidney disease
Aug
09
Association between BMI and risk of severe hypoglycaemia in type 2 diabetes.
Abstract
AIM This study aimed to assess the association between body mass index (BMI) and the development of severe hypoglycaemia in patients with type 2 diabetes (T2D), using nationwide data for the entire South Korean population. METHODS The association between BMI and severe hypoglycaemia was retrospectively examined from claims and National Health examination data registered between 2002 and 2015. A total of 1,366,692 subjects assigned clinical codes for T2D and prescribed antihypoglycaemic agents were included. The primary outcome was an episode of severe hypoglycaemia after the baseline health examination. RESULTS A total of 37,682 subjects (2.7%) experienced a new severe hypoglycaemic event during the follow-up period (mean: 8.6 years). An inverse J-shaped association was observed between BMI and severe hypoglycaemic events. The association between low BMI and high risk of severe hypoglycaemia was similar in subjects who had never smoked, did not consume alcohol, did not use insulin and had no major comorbidities, after adjusting for multiple confounding variables. This association was also found to be intensified in men, young people aged 30-49 years, those with major comorbidities and insulin users. CONCLUSION BMI and severe hypoglycaemia were found to be inversely associated. Thus, those who fall into the category of having low BMI and high risk of severe hypoglycaemia should be warned about the risk of having a hypoglycaemic event and be properly informed about hypoglycaemia to minimize the risk of fatal hypoglycaemia-related outcomes.
Yun, J-S Park, Y-M Han, K Cha, S-A Ahn, Y-B Ko, S-H
Diagnosis; Prognosis
Cardiovascular
Aug
07
Utilization Patterns of Lipid-lowering Therapies in Patients With Atherosclerotic Cardiovascular Disease or Diabetes: A Population-based Study in South Korea.
Abstract
PURPOSE We aimed to study the utilization patterns of lipid-lowering treatment (LLT), including treatment modification, adherence, and possible statin intolerance, in patients with atherosclerotic cardiovascular disease (ASCVD) or diabetes using national claims data in South Korea. METHODS A retrospective cohort study was conducted using data from the Korean Health Insurance Review & Assessment Service claims database. Patients aged ≥18 years with >1 outpatient pharmacy claim for a statin and/or ezetimibe dated January 1, 2012, to December 31, 2014, were identified and categorized into the following cohorts: patients with ASCVD, and patients with diabetes mellitus without ASCVD. LLT modification, adherence to index LLT, and possible statin intolerance were explored during the 12 months after the date of first prescription for a statin and/or ezetimibe. FINDINGS Among 1,399,872 patients who met the eligibility criteria, 807,547 (57.7%) were patients with ASCVD and 592,325 (42.3%) were patients with diabetes without ASCVD. About half of the patients had no modification in their index treatment (46.2% in the ASCVD cohort and 48.9% in the diabetes cohort), and the most common modification was permanent discontinuation (19.6% in the ASCVD cohort and 21.4% in the diabetes cohort). The mean medication possession ratios were 0.77 in the ASCVD cohort and 0.73 in the diabetes cohort and showed a decreasing trend during the 12-month follow-up period. Among patients who initiated a statin and/or ezetimibe, possible statin intolerance was observed in 53,921 patients (6.7%) in the ASCVD cohort and 42,172 patients (7.1%) in the diabetes cohort. IMPLICATIONS In South Korea, a high rate of permanent discontinuation of statin therapy in patients with ASCVD or diabetes places these patients at high risk for cardiovascular events in the future. A decreasing trend of adherence to LLT implies that more intensive education and management are required to improve therapeutic effect and reduce the risk for ASCVD. The high rate of possible statin intolerance highlights an unmet need in the prevention and management of ASCVD in South Korea.
Kim, Siin Kim, Hyungtae Kim, Eunju Han, Sola Rane, Pratik P Fox, Kathleen M Zhao, Zhongyun Qian, Yi Suh, Hae Sun
Treatment / Management
Cardiovascular
Aug
07
The impact of outpatient acute kidney injury on mortality and chronic kidney disease: a retrospective cohort study.
Abstract
Background Acute kidney injury (AKI) has been extensively studied in hospital settings. Limited data exist regarding outcomes for patients with outpatient AKI who are not subsequently admitted. We investigated whether outpatient AKI, defined by a 50% increase in creatinine (Cr), is associated with increased mortality and renal events. Methods In this retrospective study, outpatient serum Cr values from adults receiving primary care at a health system during an 18-month exposure period were used to categorize patients into one of five groups (no outpatient AKI, outpatient AKI with recovery, outpatient AKI without recovery, outpatient AKI without repeat Cr and no Cr). Principal outcomes of all-cause mortality and renal events (50% decline in estimated glomerular filtration rate to <30 mL/min/1.73 m2) were examined using Cox proportional hazards models. Results Among 384 869 eligible patients, 51% had at least one Cr measured during the exposure period. Outpatient AKI occurred in 1.4% of patients while hospital AKI occurred in only 0.3% of patients. The average follow-up was 5.3 years. Outpatient AKI was associated with an increased risk of all-cause mortality {adjusted hazard ratio [aHR] 1.90 [95% confidence interval (CI) 1.76-2.06]} and results were consistent across all AKI groups. Outpatient AKI was also associated with an increased risk of renal events [aHR 1.33 (95% CI 1.11-1.59)], even among those who recovered. Conclusions Outpatient AKI is more prevalent than inpatient AKI and is a risk factor for all-cause mortality and renal events, even among those who recover kidney function. Further research is necessary to determine risk factors and identify strategies for preventing outpatient AKI.
Leither, Maxwell D Murphy, Daniel P Bicknese, Luke Reule, Scott Vock, David M Ishani, Areef Foley, Robert N Drawz, Paul E
Diagnosis; Prognosis
Kidney disease
Aug
07
Low serum creatinine predicts risk for type 2 diabetes.
Abstract
AIMS As an insulin target tissue, skeletal muscle is inversely related to type 2 diabetes mellitus (T2DM). Serum creatinine originates mainly from creatine in muscle and is considered as a reliable surrogate marker for muscle mass in apparently healthy subjects. It is therefore hypothesized that low serum creatinine could effectively predict increased risk of T2DM. Yet information is scarce regarding the longitudinal relationship between serum creatinine and T2DM. This study aims to investigate this relation in a large general population of both men and women. METHODS A prospective cohort study (n = 57 587; follow-up range: 1-9 years, mean: 3.57 years, 95% confidence interval: 3.55-3.58 years) was conducted in a general population sample from Tianjin, China. Multivariable Cox proportional hazards regression models were used to assess the relationship between baseline serum creatinine and the risk of developing T2DM (as defined by the American Diabetes Association criteria). RESULTS During the follow-up period, 2017 subjects developed T2DM. The multivariate-adjusted hazard ratios (95% confidence interval) for T2DM incidence across quintiles of serum creatinine were 1.00 (reference), 0.86 (0.75, 0.99), 0.82 (0.72, 0.94), 0.85 (0.74, 0.97), and 0.77 (0.67, 0.89; P for trend <.01). Similar results were observed in both sexes (interaction P = .56). CONCLUSIONS These findings indicate that serum creatinine concentration is inversely related to incident T2DM in both men and women. Measuring serum creatinine may assist in the early detection of individuals at high risk of developing T2DM.
Bao, Xue Gu, Yeqing Zhang, Qing Liu, Li Meng, Ge Wu, Hongmei Xia, Yang Shi, Hongbin Wang, Honglei Sun, Shaomei Wang, Xing Zhou, Ming Jia, Qiyu Song, Kun Niu, Kaijun
Diagnosis; Prognosis
Diabetes
Aug
06
Pioglitazone and cause-specific risk of mortality in patients with type 2 diabetes: extended analysis from a European multidatabase cohort study.
Abstract
Objectives Describe and compare the risk of cardiovascular and non-cardiovascular mortality in patients whose antidiabetic therapy is modified to include pioglitazone compared with an alternative antidiabetic medication at the same stage of disease progression. Research design and methods This exploratory linked database cohort analysis used pooled health and mortality data from three European countries: Finland, Sweden and the UK. Propensity score together with exact matching was used to match 31 133 patients with type 2 diabetes first prescribed pioglitazone from 2000 to 2011, to 31 133 patients never prescribed pioglitazone. Exact matching variables were treatment stage, history of diabetes, diabetes complications and cardiovascular disease, and year of cohort entry. Mean follow-up time was 2.60 (SD 2.00) and 2.69 (SD 2.31) years in the pioglitazone and non-pioglitazone-exposed groups, respectively. Crude cause-specific mortality rates were ascertained. Association with pioglitazone use was estimated using Cox proportional hazards models adjusted a priori for country, age, sex, the propensity score quintile and time-dependent variables representing use of antidiabetic drugs. Stepwise testing identified no additional confounders to include in adjusted models. Results The crude mortality rate was lower in the pioglitazone-exposed group than the non-exposed group for both cardiovascular and non-cardiovascular mortality. Adjusted HRs comparing pioglitazone to alternative antidiabetic exposure were 0.58 (95% CI 0.52 to 0.63) and 0.63 (95% CI 0.58 to 0.68) for cardiovascular and non-cardiovascular mortality, respectively. A protective effect associated with pioglitazone was also found for all specific cardiovascular causes. Conclusions This analysis suggests that pioglitazone is associated with a decrease in both cardiovascular and non-cardiovascular mortality. Results should be interpreted with caution due to the potential for residual confounding in this exploratory analysis. Further studies, specifically designed to test the association between pioglitazone use and patient-focused outcomes, are suggested. Study registration number European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP; EUPAS3626).
Strongman, Helen Christopher, Solomon Majak, Maila Williams, Rachael Bahmanyar, Shahram Linder, Marie Heintjes, Edith M Bennett, Dimitri Korhonen, Pasi Hoti, Fabian
Treatment / Management
Diabetes
Aug
06
Mean HbA, HbA variability, and mortality in people with diabetes aged 70 years and older: a retrospective cohort study.
Abstract
BACKGROUND Glycaemic targets for older people have been revised in recent years because of concern that more stringent targets are associated with increased mortality. We aimed to investigate the association between glycaemic control (mean HbA) and variability (variability of HbA over time) and mortality in older people with diabetes. METHODS We did a 5-year retrospective cohort study using The Health Improvement Network database, which includes data from 587 UK primary care practices. We included patients of either sex who were aged 70 years and older with type 1 or type 2 diabetes. The primary outcome was time to all-cause mortality. Our primary exposure variables were mean HbA and variability of HbA over time. The observation included a 4-year run-in period (from 2003) as a baseline, with a 5-year follow-up (from 2007 to 2012). We assessed mean HbA in three models: a baseline mean HbA for 2003-06 (model 1), the mean across the whole follow-up period (model 2), and a time-varying yearly updated mean (model 3). A variability score (from 0 [low] to 100 [high]) was calculated on the basis of number of changes in HbA of 0·5% (5·5 mmol/mol) or more from 2003 to 2012 or to the point of mortality, based on changes in the annual mean as per each model with a minimum of six readings. FINDINGS The cohort consisted of 54 803 people, of whom 17 680 (8614 [30·7%] of 28 017 women and 9066 [33·8%] of 26 786 men) died during the observation period. The overall mortality rate was 77 per 1000 person-years (73 per 1000 person-years for women and 80 per 1000 person-years for men). The data showed a J-shaped distribution for mortality risk in both sexes, with significant increases with HbA values greater than 8% (64 mmol/mol) and less than 6% (42 mmol/mol), although excess mortality risk was non-significant in model 1 for men at HbA values of 8% (64 mmol/mol) to less than 8·5% (<69 mmol/mol) and in models 1 and 3 for both sexes assessed individually at HbA values less than 6% (42 mmol/mol). Mortality increased substantially with increasing HbA variability in all models (overall and for both sexes). For the model 2 HbA measure, the adjusted hazard ratios comparing patients with a glycaemic variability score of more than 80 to 100 with those with a score of 0 to 20 were 2·47 (95% CI 2·08-2·93) for women and 2·21 (1·87-2·61) for men. Fitting the mean HbA models with the glycaemic variability score altered the risk distribution; this observation was most marked in the model 2 analysis, in which a significant increased risk was only apparent with HbA values greater than 9·5% (80 mmol/mol) in women and 9% (75 mmol/mol) in men. INTERPRETATION Both low and high levels of glycaemic control were associated with an increased mortality risk, and the level of variability also seems to be an important factor, suggesting that a stable glycaemic level in the middle range is associated with lower risk. Glycaemic variability, as assessed by variability over time in HbA, might be an important factor in understanding mortality risk in older people with diabetes. FUNDING King's College London and Diabetes Frail.
Forbes, Angus Murrells, Trevor Mulnier, Henrietta Sinclair, Alan J
Diagnosis; Prognosis
Diabetes
Jul
03
Ischaemic stroke, haemorrhage, and mortality in older patients with chronic kidney disease newly started on anticoagulation for atrial fibrillation: a population based study from UK primary care.
Abstract
OBJECTIVE To assess the association between anticoagulation, ischaemic stroke, gastrointestinal and cerebral haemorrhage, and all cause mortality in older people with atrial fibrillation and chronic kidney disease. DESIGN Propensity matched, population based, retrospective cohort analysis from January 2006 through December 2016. SETTING The Royal College of General Practitioners Research and Surveillance Centre database population of almost 2.73 million patients from 110 general practices across England and Wales. PARTICIPANTS Patients aged 65 years and over with a new diagnosis of atrial fibrillation and estimated glomerular filtration rate (eGFR) of <50 mL/min/1.73m, calculated using the chronic kidney disease epidemiology collaboration creatinine equation. Patients with a previous diagnosis of atrial fibrillation or receiving anticoagulation in the preceding 120 days were excluded, as were patients requiring dialysis and recipients of renal transplants. INTERVENTION Receipt of an anticoagulant prescription within 60 days of atrial fibrillation diagnosis. MAIN OUTCOME MEASURES Ischaemic stroke, cerebral or gastrointestinal haemorrhage, and all cause mortality. RESULTS 6977 patients with chronic kidney disease and newly diagnosed atrial fibrillation were identified, of whom 2434 were on anticoagulants within 60 days of diagnosis and 4543 were not. 2434 pairs were matched using propensity scores by exposure to anticoagulant or none and followed for a median of 506 days. The crude rates for ischaemic stroke and haemorrhage were 4.6 and 1.2 after taking anticoagulants and 1.5 and 0.4 in patients who were not taking anticoagulant per 100 person years, respectively. The hazard ratios for ischaemic stroke, haemorrhage, and all cause mortality for those on anticoagulants were 2.60 (95% confidence interval 2.00 to 3.38), 2.42 (1.44 to 4.05), and 0.82 (0.74 to 0.91) compared with those who received no anticoagulation. CONCLUSION Giving anticoagulants to older people with concomitant atrial fibrillation and chronic kidney disease was associated with an increased rate of ischaemic stroke and haemorrhage but a paradoxical lowered rate of all cause mortality. Careful consideration should be given before starting anticoagulants in older people with chronic kidney disease who develop atrial fibrillation. There remains an urgent need for adequately powered randomised trials in this population to explore these findings and to provide clarity on correct clinical management.
Kumar, Shankar de Lusignan, Simon McGovern, Andrew Correa, Ana Hriskova, Mariya Gatenby, Piers Jones, Simon Goldsmith, David Camm, A John
Treatment / Management
Cardiovascular, Kidney disease
Jul
05
Trajectories of Long-Term Normal Fasting Plasma Glucose and Risk of Coronary Heart Disease: A Prospective Cohort Study.
Abstract
BACKGROUND Fasting plasma glucose (FPG) levels can vary over time and its longitudinal changing patterns may predict cardiometabolic risk. We aim to identify different trajectories of FPG in those who remained normoglycemic and investigate the association between trajectory groups and coronary heart disease risk in a large prospective cohort study. METHODS AND RESULTS A total of 20 514 subjects between ages 20 and 80 years were included at baseline. All participants had maintained normal FPG throughout an average follow-up period of 5.8 years. We identified 3 distinct trajectories using a group-based trajectory model, labeled by initial value and changing pattern: low-increasing (n=12 694), high-increasing-decreasing (n=5330), and high-decreasing-increasing (n=2490). The coronary heart disease incidence density among these 3 groups (3.00, 4.05, and 3.26 per 1000 person-years, respectively) was significantly different (=0.038). The high-increasing-decreasing group was characterized by a starting FPG of 4.80 mmol/L, and increased up to 5.42 mmol/L at age 55, then decreased thereafter. Treating the low-increasing group as the reference, the age- and sex-adjusted hazard ratio was 1.58 (95% confidence interval, 1.23-2.02) for the high-increasing-decreasing group by Cox proportional hazard regression. After adjustment for other potential confounding factors, the hazard ratio is 1.40 (95% confidence interval, 1.08-1.81). The association persisted after adjustment for baseline FPG, mean, or SD of FPG. CONCLUSIONS Distinct trajectories of long-term normal FPG are associated with the development of coronary heart disease, which is independent of other metabolic factors including FPG levels. These findings have implications for intervention and prevention of coronary heart disease among individuals who are normoglycemic.
Yuan, Zhongshang Yang, Yang Wang, Chunxia Liu, Jing Sun, Xiubin Liu, Yi Li, Shengxu Xue, Fuzhong
Diagnosis; Prognosis
Cardiovascular
Jul
08
Invasive Dental Treatment and Risk for a First Myocardial Infarction.
Abstract
Invasive dental treatment is suggested to be associated with an increased risk for the development of cardiovascular events. We tested the hypothesis that the incidence of a first myocardial infarction (MI) within 4 wk after invasive dental treatments is increased. A registry-based case-control study within nationwide health care and population registries in Sweden was performed. The case patients included 51,880 individuals with a first fatal or nonfatal MI between January 2011 and December 2013. For each case, 5 control subjects, free from prior MI and matched for age, sex, and geographic area of residence, were randomly selected from the national population registry through risk set sampling with replacement, resulting in 246,978 control subjects. Information on dental treatments was obtained from the Dental Health Register, and the procedures were categorized into invasive dental treatments or other dental treatments. Conditional logistic regression was used to estimate odds ratios (ORs) for MI with corresponding 95% confidence intervals (CIs). In addition to the matching variables, adjustments were made for the following confounders: diabetes, previous cardiovascular disease (CVD), CVD drug treatment, education, and income. The mean age for case patients and controls subjects was 72.6 ± 13.0 y and 72.3 ± 13.0 y, respectively. Case patients more often had previous CVD (49% vs. 23%; P < 0.001) and diabetes (19% vs. 11%; P < 0.001) and received more treatment with CVD drugs (68% vs. 56%; P < 0.001) than control subjects. There was no association between invasive dental treatments during the 4 wk preceding the MI index date (crude OR = 0.99; 95% CI, 0.92 to 1.06; adjusted for confounders OR = 0.98; 95% CI, 0.91 to 1.06). This study did not support the hypothesis of an increased incidence of MI after recent invasive dental treatment.
Nordendahl, E Kjellström, B Fored, C M Ekbom, A Svensson, T Norhammar, A Gustafsson, A
Diagnosis; Prognosis
Cardiovascular
May
09
Lipid profile and incidence of atrial fibrillation: A prospective cohort study in China.
Abstract
BACKGROUND The association between dyslipidemia, a major risk factor for cardiovascular diseases, and atrial fibrillation (AF) is not clear because of limited evidence. HYPOTHESIS Dyslipidemia may be associated with increased risk of AF in a Chinese population. METHODS A total of 88 785 participants free from AF at baseline (2006-2007) were identified from the Kailuan Study. Fasting levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were measured at baseline using standard procedures. The study population was stratified based on quartiles of lipid profile. Incident AF was ascertained from electrocardiograms at biennial follow-up visits (2008-2015). The associations between incident AF and the different lipid parameters (TC, LDL-C, HDL-C, and TG) were assessed by Cox proportional hazards regression analysis. RESULTS Over a mean follow-up period of 7.12 years, 328 subjects developed AF. Higher TC (hazard ratio [HR]: 0.60, 95% confidence interval [CI]: 0.43-0.84) and LDL-C (HR: 0.60, 95% CI: 0.43-0.83) levels were inversely associated with incident AF after multivariable adjustment. HDL-C and TG levels showed no association with newly developed AF. The results remained consistent after exclusion of individuals with myocardial infarction or cerebral infarction, or those on lipid-lowering therapy. Both TC/HDL-C and LDL-C/HDL-C ratios were inversely associated with risk of AF (per unit increment, HR: 0.88, 95% CI: 0.79-0.98 and HR: 0.77, 95% CI: 0.66-0.91, respectively). CONCLUSIONS TC and LDL-C levels were inversely associated with incident AF, whereas no significant association of AF with HDL-C or TG levels was observed.
Li, Xintao Gao, Lianjun Wang, Zhao Guan, Bo Guan, Xumin Wang, Binhao Han, Xu Xiao, Xianjie Waleed, Khalid Bin Chandran, Clarance Wu, Shouling Xia, Yunlong
Diagnosis; Prognosis
Cardiovascular
Jul
04
Use of haloperidol versus atypical antipsychotics and risk of in-hospital death in patients with acute myocardial infarction: cohort study.
Abstract
OBJECTIVE To compare the risk of in-hospital mortality associated with haloperidol compared with atypical antipsychotics in patients admitted to hospital with acute myocardial infarction. DESIGN Cohort study using a healthcare database. SETTING Nationwide sample of patient data from more than 700 hospitals across the United States. PARTICIPANTS 6578 medical patients aged more than 18 years who initiated oral haloperidol or oral atypical antipsychotics (olanzapine, quetiapine, risperidone) during a hospital admission with a primary diagnosis of acute myocardial infarction between 2003 and 2014. MAIN OUTCOME MEASURE In-hospital mortality during seven days of follow-up from treatment initiation. RESULTS Among 6578 patients (mean age 75.2 years) treated with an oral antipsychotic drug, 1668 (25.4%) initiated haloperidol and 4910 (74.6%) initiated atypical antipsychotics. The mean time from admission to start of treatment (5.3 5.6 days) and length of stay (12.5 13.6 days) were similar, but the mean treatment duration was shorter in patients using haloperidol compared with those using atypical antipsychotics (2.4 3.9 days). 1:1 propensity score matching was used to adjust for confounding. In intention to treat analyses with the matched cohort, the absolute rate of death per 100 person days was 1.7 for haloperidol (129 deaths) and 1.1 for atypical antipsychotics (92 deaths) during seven days of follow-up from treatment initiation. The survival probability was 0.93 in patients using haloperidol and 0.94 in those using atypical antipsychotics at day 7, accounting for the loss of follow-up due to hospital discharge. The unadjusted and adjusted hazard ratios of death were 1.51 (95% confidence interval 1.22 to 1.85) and 1.50 (1.14 to 1.96), respectively. The association was strongest during the first four days of follow-up and decreased over time. By day 5, the increased risk was no longer evident (1.12, 0.79 to 1.59). In the as-treated analyses, the unadjusted and adjusted hazard ratios were 1.90 (1.43 to 2.53) and 1.93 (1.34 to 2.76), respectively. CONCLUSION The results suggest a small increased risk of death within seven days of initiating haloperidol compared with initiating an atypical antipsychotic in patients with acute myocardial infarction. Although residual confounding cannot be excluded, this finding deserves consideration when haloperidol is used for patients admitted to hospital with cardiac morbidity.
Park, Yoonyoung Bateman, Brian T Kim, Dae Hyun Hernandez-Diaz, Sonia Patorno, Elisabetta Glynn, Robert J Mogun, Helen Huybrechts, Krista F
Treatment / Management
Cardiovascular
Jun
09
Sodium-glucose co-transporter-2 inhibitors and the risk of ketoacidosis in patients with type 2 diabetes mellitus: A nationwide population-based cohort study.
Abstract
AIMS To estimate the risk of diabetic ketoacidosis (DKA) associated with sodium-glucose co-transporter-2 (SGLT2) inhibitor treatment compared with the risk associated with dipeptidyl-peptidase-4 (DPP-4) inhibitor treatment. METHODS A nationwide population-based cohort study using claims data from the Korean Health Insurance Review and Assessment Service from January 1, 2013 to June 30, 2017 was performed. A total of 56 325 patients who were started on SGLT2 inhibitors were included in this study and were matched with same number of patients who were started on DPP-4 inhibitors using propensity score matching. Kaplan-Meier curves and Cox proportional hazards regression analyses were used to estimate the risk of hospitalization for DKA. RESULTS The risk of hospitalization for DKA was not increased in SGLT2 inhibitor users vs DPP-4 inhibitor users (hazard ratio [HR] 0.956, 95% confidence interval [CI] 0.581-1.572; P = .996). The incidence rate of hospitalization for DKA during the first 30 days after initiation of the SGLT2 inhibitor was 2.501 cases per 1000 person-years, which was higher than the rate during 3 years (0.614 cases per 1000 person-years). SGLT2 inhibitor use was associated with a higher HR in patients with diabetic microvascular complications (HR 2.044, 95% CI 0.900-4.640; P = .088) and in patients taking diuretics (HR 3.648, 95% CI 0.720-18.480; P = .118), although these associations were not statistically significant. CONCLUSION We found that SGLT2 inhibitor treatment did not increase the risk of DKA compared with DPP-4 inhibitor treatment. Our findings suggest that patients prescribed diuretics or those with microvascular complications may have a greater tendency to be hospitalized for DKA.
Kim, Young-Gun Jeon, Ja Young Han, Seung Jin Kim, Dae Jung Lee, Kwan-Woo Kim, Hae Jin
Treatment / Management
Diabetes
Jun
10
Rates of myocardial infarction and stroke in patients initiating treatment with SGLT2-inhibitors versus other glucose-lowering agents in real-world clinical practice: Results from the CVD-REAL study.
Abstract
The multinational, observational CVD-REAL study recently showed that initiation of sodium-glucose co-transporter-2 inhibitors (SGLT-2i) was associated with significantly lower rates of death and heart failure vs other glucose-lowering drugs (oGLDs). This sub-analysis of the CVD-REAL study sought to determine the association between initiation of SGLT-2i vs oGLDs and rates of myocardial infarction (MI) and stroke. Medical records, claims and national registers from the USA, Sweden, Norway and Denmark were used to identify patients with T2D who newly initiated treatment with SGLT-2i (canagliflozin, dapagliflozin or empagliflozin) or oGLDs. A non-parsimonious propensity score was developed within each country to predict initiation of SGLT-2i, and patients were matched 1:1 in the treatment groups. Pooled hazard ratios (HRs) and 95% CIs were generated using Cox regression models. Overall, 205 160 patients were included. In the intent-to-treat analysis, over 188 551 and 188 678 person-years of follow-up (MI and stroke, respectively), there were 1077 MI and 968 stroke events. Initiation of SGLT-2i vs oGLD was associated with a modestly lower risk of MI and stroke (MI: HR, 0.85; 95%CI, 0.72-1.00; P = .05; Stroke: HR, 0.83; 95% CI, 0.71-0.97; P = .02). These findings complement the results of the cardiovascular outcomes trials, and offer additional reassurance with regard to the cardiovascular effects of SGLT-2i, specifically as it relates to ischaemic events.
Kosiborod, Mikhail Birkeland, Kåre I Cavender, Matthew A Fu, Alex Z Wilding, John P Khunti, Kamlesh Holl, Reinhard W Norhammar, Anna Jørgensen, Marit E Wittbrodt, Eric T Thuresson, Marcus Bodegård, Johan Hammar, Niklas Fenici, Peter ,
Treatment / Management
Cardiovascular
Jul
01
Socioeconomic inequality in medication persistence in primary and secondary prevention of coronary heart disease - A population-wide electronic cohort study.
Abstract
BACKGROUND Coronary heart disease (CHD) mortality in England fell by 36% between 2000 and 2007 and it is estimated that approximately 50% of the fall was due to improved treatment uptake. Marked socio-economic inequalities in CHD mortality in the United Kingdom (UK) remain, with higher age-adjusted rates in more deprived groups. Inequalities in the persistence of medication for primary and secondary prevention of CHD may contribute to the observed social gradient and we investigated this possibility in the population of Wales (UK). METHODS AND FINDINGS An electronic cohort of individuals aged over 20 (n = 1,199,342) in Wales (UK) was formed using linked data from primary and secondary care and followed for six years (2004-2010). We identified indications for medication (statins, aspirin, ACE inhibitors, clopidogrel) recommended in UK National Institute for Clinical Excellence (NICE) guidance for CHD (high risk, stable angina, stable angina plus diabetes, unstable angina, and myocardial infarction) and measured the persistence of indicated medication (time from initiation to discontinuation) across quintiles of the Welsh Index of Multiple Deprivation, an area-based measure of socio-economic inequality, using Cox regression frailty models. In models adjusted for demographic factors, CHD risk and comorbidities across 15 comparisons for persistence of the medications, none favoured the least deprived quintile, two favoured the most deprived quintile and 13 showed no significant differences. CONCLUSIONS During our study period (2004-2010) we found no significant evidence of socio-economic inequality in the persistence of recommended medication for primary and secondary prevention of CHD.
King, William Lacey, Arron White, James Farewell, Daniel Dunstan, Frank Fone, David
Causes and Prevention
Cardiovascular
Jul
01
One-Year Clinical Effectiveness Comparison of Prasugrel with Ticagrelor: Results from a Retrospective Observational Study using an Integrated Claims Database.
Abstract
BACKGROUND No direct comparisons of ticagrelor and prasugrel with 1-year clinical follow-up have been reported. OBJECTIVES Our objective was to compare 1-year clinical outcomes among patients with acute coronary syndrome (ACS) managed with percutaneous coronary intervention (PCI) and treated with either ticagrelor or prasugrel in a real-world setting. METHODS This retrospective study included patients from a payer database who were aged ≥18 years and had ACS managed with PCI with no history of transient ischemic attack (TIA)/stroke. Data were propensity matched for prasugrel use with a 3:1 prasugrel:ticagrelor ratio. Post-discharge net adverse clinical event (NACE) rate at 1 year was evaluated for noninferiority using a pre-defined 20% margin. NACE was a composite of major adverse cardiovascular events (MACE) or rehospitalization for bleeding. RESULTS In total, 15,788 ACS-PCI patients were included (prasugrel 12,797; ticagrelor 2991). Prasugrel-treated patients were younger; less likely to be female, have prior myocardial infarction (MI), diabetes, or non-ST-segment elevation MI (NSTEMI); and more likely to have unstable angina (UA) than ticagrelor-treated patients. Prior to matching, NACE and MACE (P < 0.01) were lower, with no difference in bleeding with prasugrel compared with ticagrelor. After matching, there was no significant difference in baseline characteristics. Noninferiority was demonstrated for NACE, MACE, and bleeding between prasugrel and ticagrelor. NACE and MACE were significantly lower with prasugrel use, primarily driven by heart failure, with no significant difference in all-cause death, MI, UA, revascularization, TIA/stroke, or bleeding. CONCLUSIONS In this retrospective study, physicians preferentially used prasugrel rather than ticagrelor in younger ACS-PCI patients with lower risk of bleeding or comorbidities. After propensity matching, clinical outcomes associated with prasugrel were noninferior to those with ticagrelor.
Effron, Mark B Nair, Kavita V Molife, Cliff Keller, Stuart Y Page, Robert L Simeone, Jason C Murphy, Brian Nordstrom, Beth L Zhu, Yajun McCollam, Patrick L Vetrovec, George W
Treatment / Management
Cardiovascular
Jun
09
Real-world evidence of superiority of endovascular repair in treating ruptured abdominal aortic aneurysm.
Abstract
OBJECTIVE The majority of previous studies, including randomized controlled trials, have failed to provide sufficient evidence of superiority of endovascular aneurysm repair (EVAR) over open aortic repair (OAR) of ruptured abdominal aortic aneurysm (rAAA) while comparing mortality and complications. This is in part due to small study size, patient selection bias, scarce adjustment for essential variables, single insurance type, or selection of only older patients. This study aimed to provide real-world, contemporary, comprehensive, and robust evidence on mortality of EVAR vs OAR of rAAA. METHODS A retrospective observational cohort study was performed of rAAA patients registered in the Premier Healthcare Database between July 2009 and March 2015. A multivariate logistic regression model was operated to estimate the association between procedure types (OAR vs EVAR) and in-hospital mortality. The final model was adjusted for demographics (age, sex, race, marital status, and geographic region), hospital characteristics (urban or rural, teaching or not), and potential confounders (hypertension, diabetes, hypercholesterolemia, obesity, ischemic heart disease, chronic kidney disease, symptoms of critical limb ischemia, chronic obstructive pulmonary disease, smoking, and alcoholism). Furthermore, coarsened exact matching was applied to substantiate the result in the matched cohort. RESULTS There were a total of 3164 patients with rAAA (1550 [49.0%] OAR and 1614 [51.0%] EVAR). Mortality was 23.79% in the EVAR group compared with 36.26% in the OAR group (P < .001). The adjusted odds ratios of mortality (1.91; 95% confidence interval [CI], 1.62-2.25; P < .001), cardiac complication (1.54; 95% CI, 1.22-1.96; P < .001), pulmonary failure (1.90; 95% CI, 1.60-2.24; P < .001), renal failure (1.90; 95% CI, 1.61-2.23; P < .001), and bowel ischemia (2.40; 95% CI, 1.70-3.35; P < .001) were significantly higher after OAR compared with EVAR. We further applied coarsened exact matching, which followed the same pattern of mortality (odds ratio, 1.68; 95% CI 1.41-1.99; P < .001) and all major complications. CONCLUSIONS Although the choice of repair of rAAA is highly dependent on the experience of the operating team and the anatomic suitability of the patient, this contemporary analysis of a large cohort of rAAA showed significantly higher adjusted risk of mortality in OAR compared with EVAR and substantially higher complications.
Gupta, Akshay Kumar Dakour Aridi, Hanaa Locham, Satinderjit Nejim, Besma Veith, Frank J Malas, Mahmoud B
Diagnosis; Prognosis
Cardiovascular
May
09
Can traditional risk factors explain the higher risk of cardiovascular disease in South Asians compared to Europeans in Norway and New Zealand? Two cohort studies.
Abstract
OBJECTIVES The objective was to prospectively examine potential differences in the risk of first cardiovascular disease (CVD) events between South Asians and Europeans living in Norway and New Zealand, and to investigate whether traditional risk factors could explain any differences. METHODS We included participants (30-74 years) without prior CVD in a Norwegian (n=16 606) and a New Zealand (n=129 449) cohort. Ethnicity and cardiovascular risk factor information was linked with hospital registry data and cause of death registries to identify subsequent CVD events. We used Cox proportional hazards regression to investigate the relationship between risk factors and subsequent CVD for South Asians and Europeans, and to calculate age-adjusted HRs for CVD in South Asians versus Europeans in the two cohorts separately. We sequentially added the major CVD risk factors (blood pressure, lipids, diabetes and smoking) to study their explanatory role in observed ethnic CVD risk differences. RESULTS South Asians had higher total cholesterol (TC)/high-density lipoprotein (HDL) ratio and more diabetes at baseline than Europeans, but lower blood pressure and smoking levels. South Asians had increased age-adjusted risk of CVD compared with Europeans (87%-92% higher in the Norwegian cohort and 42%-75% higher in the New Zealand cohort) and remained with significantly increased risk after adjusting for all major CVD risk factors. Adjusted HRs for South Asians versus Europeans in the Norwegian cohort were 1.57 (95% CI 1.19 to 2.07) in men and 1.76 (95% CI 1.09 to 2.82) in women. Corresponding figures for the New Zealand cohort were 1.64 (95% CI 1.43 to 1.88) in men and 1.39 (95% CI 1.11 to 1.73) in women. CONCLUSION Differences in TC/HDL ratio and diabetes appear to explain some of the excess risk of CVD in South Asians compared with Europeans. Preventing dyslipidaemia and diabetes in South Asians may therefore help reduce their excess risk of CVD.
Rabanal, Kjersti S Meyer, Haakon E Tell, Grethe S Igland, Jannicke Pylypchuk, Romana Mehta, Suneela Kumar, Bernadette Jenum, Anne Karen Selmer, Randi M Jackson, Rod
Causes and Prevention
Cardiovascular
May
15
An electronic health records cohort study on heart failure following myocardial infarction in England: incidence and predictors.
Abstract
OBJECTIVES To investigate the incidence and determinants of heart failure (HF) following a myocardial infarction (MI) in a contemporary cohort of patients with MI using routinely collected primary and hospital care electronic health records (EHRs). METHODS Data were used from the CALIBER programme, linking EHRs in England from primary care, hospital admissions, an MI registry and mortality data. Subjects were eligible if they were 18 years or older, did not have a history of HF and survived a first MI. Factors associated with time to HF were examined using Cox proportional hazard models. RESULTS Of the 24 479 patients with MI, 5775 (23.6%) developed HF during a median follow-up of 3.7 years (incidence rate per 1000 person-years: 63.8, 95% CI 62.2 to 65.5). Baseline characteristics significantly associated with developing HF were: atrial fibrillation (HR 1.62, 95% CI 1.51 to 1.75), age (per 10 years increase: 1.45, 1.41 to 1.49), diabetes (1.45, 1.35 to 1.56), peripheral arterial disease (1.38, 1.26 to 1.51), chronic obstructive pulmonary disease (1.28, 1.17 to 1.40), greater socioeconomic deprivation (5th vs 1st quintile: 1.27, 1.13 to 1.41), ST-segment elevation MI at presentation (1.19, 1.11 to 1.27) and hypertension (1.16, 1.09 to 1.23). Results were robust to various sensitivity analyses such as competing risk analysis and multiple imputation. CONCLUSION In England, one in four survivors of a first MI develop HF within 4 years. This contemporary study demonstrates that patients with MI are at considerable risk of HF. Baseline patient characteristics associated with time until HF were identified, which may be used to target preventive strategies.
Gho, Johannes M I H Schmidt, Amand F Pasea, Laura Koudstaal, Stefan Pujades-Rodriguez, Mar Denaxas, Spiros Shah, Anoop D Patel, Riyaz S Gale, Chris P Hoes, Arno W Cleland, John G Hemingway, Harry Asselbergs, Folkert W
Diagnosis; Prognosis
Cardiovascular
Jul
09
Utilization Patterns of Glucagon-Like Peptide-1 Receptor Agonists in Patients with Type 2 Diabetes Mellitus in Italy: A Retrospective Cohort Study.
Abstract
INTRODUCTION Real-world evidence on glucagon-like peptide-1 receptor agonist (GLP-1 RAs) usage is emerging in different European countries but is lacking in Italy. This retrospective cohort study aimed to describe the real-world drug utilization patterns in patients initiating GLP-1 RAs for treating T2DM in Italy. METHODS Adults aged ≥ 20 years and with ≥ 1 oral antidiabetic drug (alone or in combination with insulin) other than GLP-1 RAs in the 6 months prior to initiating exenatide twice daily (exBID), exenatide once weekly (exQW), dulaglutide once weekly (DULA), liraglutide once daily (LIRA) or lixisenatide once daily (LIXI) between March and July 2016 were retrospectively identified in the Italian IMS LifeLink™ longitudinal prescriptions database (retail pharmacy data). Patients with ≥ 6-month follow-up (defined as evidence of any prescription activity) were included. Proportions of patients who remained persistent (continued treatment until discontinuation/switch) in the first 6 months and of those who discontinued or switched to a different GLP-1 RA over the entire follow-up were recorded. For each treatment, the average daily/weekly dosage (ADD/AWD) while persistent during the available follow-up was calculated. RESULTS We identified 7319 patients: 92 exBID, 970 exQW, 3368 DULA, 2573 LIRA and 316 LIXI. Across treatments, 89% patients were ≥ 50 years old, 54% were males, and the median follow-up duration ranged between 8.1 and 8.7 months. At 6 months, 35% exBID, 47% exQW, 62% DULA, 50% LIRA and 40% LIXI patients remained persistent. Over the entire follow-up, median persistence days varied from 73 (exBID) to > 300 days (DULA). The mean ± SD ADD/AWD was exBID: 17.7 ± 2.1 µg/day; exQW: 2.1 ± 0.1 mg/week; DULA: 1.5 ± 0.2 mg/week; LIRA: 1.5 ± 0.2 mg/day; LIXI: 21.0 ± 5.5 µg/day. CONCLUSIONS This real-world analysis suggests differences exist in persistence between patients treated with various GLP-1 RAs. Among the investigated treatments, patients prescribed exBID recorded the lowest and those prescribed DULA the highest persistence with therapy. FUNDING Eli Lilly and Co., Indianapolis, IN, USA.
Federici, Marco Orsini McQuillan, Janette Biricolti, Giovanni Losi, Serena Lebrec, Jeremie Richards, Catrina Miglio, Cristiana Norrbacka, Kirsi
Treatment / Management
Diabetes
May
02
Comparative effectiveness of novel oral anticoagulants in UK patients with non-valvular atrial fibrillation and chronic kidney disease: a matched cohort study.
Abstract
OBJECTIVES To evaluate the effectiveness and safety of novel oral anticoagulants (NOACs) compared with vitamin K antagonists (VKAs) among patients with non-valvular atrial fibrillation (NVAF), particularly those with chronic kidney disease (CKD). DESIGN Population-based matched cohort study. SETTING Over 670 primary care practices in the UK, contributing to the Clinical Practice Research Datalink. PARTICIPANTS Up to 6818 adult patients newly treated with NOACs between 2011 and 2016, matched 1:1 to new users of VKAs on age, sex and high-dimensional propensity score. INTERVENTIONS Current exposure to NOACs compared with current exposure to VKAs. MAIN OUTCOME MEASURES HRs of ischaemic stroke and systemic embolism (SE), major bleeding, gastrointestinal (GI) bleeding, intracranial bleeding, myocardial infarction and all-cause mortality. RESULTS In as-treated analyses, the rates of ischaemic stroke/SE were similar between NOACs and VKAs (HR 0.94; 95% CI 0.62 to 1.42), as were the rates of major bleeding (HR 0.86; 95% CI 0.56 to 1.33). NOACs also significantly increased the risk of GI bleeding (HR 1.78; 95% CI 1.27 to 2.48). In patients with NVAF and CKD, NOACs and VKAs remained comparable with respect to the risk of ischaemic stroke/SE (HR 0.79; 95% CI 0.40 to 1.58) and major bleeding (HR 0.88; 95% CI 0.47 to 1.62), with no difference in the risk of GI bleeding (HR 0.99; 95% CI 0.63 to 1.55). Similar results were obtained in on-treatment analyses using a time-dependent exposure definition. CONCLUSIONS Our results suggest that in the UK primary care, NOACs are overall effective and safe alternatives to VKAs, among patients with NVAF altogether, as well as in patients with NVAF and CKD.
Loo, Simone Y Coulombe, Janie Dell'Aniello, Sophie Brophy, James M Suissa, Samy Renoux, Christel
Treatment / Management
Cardiovascular, Kidney disease
Jun
07
Probability of Achieving Glycemic Control with Basal Insulin in Patients with Type 2 Diabetes in Real-World Practice in the USA.
Abstract
INTRODUCTION Basal insulin (BI) plays an important role in treating type 2 diabetes (T2D), especially when oral antidiabetic (OAD) medications are insufficient for glycemic control. We conducted a retrospective, observational study using electronic medical records (EMR) data from the IBM Explorys database to evaluate the probability of achieving glycemic control over 24 months after BI initiation in patients with T2D in the USA. METHODS A cohort of 6597 patients with T2D who started BI following OAD(s) and had at least one valid glycated hemoglobin (HbA1c) result recorded both within 90 days before and 720 days after BI initiation were selected. We estimated the changes from baseline in HbA1c every 6 months, the quarterly conditional probabilities of reaching HbA1c < 7% if a patient had not achieved glycemic control prior to each quarter (Q), and the cumulative probability of reaching glycemic control over 24 months. RESULTS Our cohort was representative of patients with T2D who initiated BI from OADs in the USA. The average HbA1c was 9.1% at BI initiation, and decreased robustly (1.5%) in the first 6 months after initiation with no further reductions thereafter. The conditional probability of reaching glycemic control decreased rapidly in the first year (26.6% in Q2; 17.6% in Q3; 8.6% in Q4), and then remained low (≤ 6.1%) for each quarter in the second year. Cumulatively, about 38% of patients reached HbA1c < 7% in the first year; only approximately 8% more did so in the second year. CONCLUSION Our study of real-world data from a large US EMR database suggested that among patients with T2D who initiated BI after OADs, the likelihood of reaching glycemic control diminished over time, and remained low from 12 months onwards. Additional treatment options should be considered if patients do not reach glycemic control within 12 months of BI initiation. FUNDING Sanofi Corporation.
Blonde, Lawrence Meneghini, Luigi Peng, Xuejun Victor Boss, Anders Rhee, Kyu Shaunik, Alka Kumar, Supriya Balodi, Sidhartha Brulle-Wohlhueter, Claire McCrimmon, Rory J
Treatment / Management
Diabetes
May
15
Prospective Study of Fasting Blood Glucose and Intracerebral Hemorrhagic Risk.
Abstract
BACKGROUND AND PURPOSE Although diabetes mellitus is an established independent risk factor for ischemic stroke, the association between fasting blood glucose and intracerebral hemorrhage (ICH) is limited and inconsistent. The objective of the current study was to examine the potential impact of long-term fasting blood glucose concentration on subsequent risk of ICH. METHODS This prospective study included 96 110 participants of the Kailuan study, living in Kailuan community, Tangshan city, China, who were free of cardiovascular diseases and cancer at baseline (2006). Fasting blood glucose concentration was measured in 2006, 2008, 2010, and 2012. Updated cumulative average fasting blood glucose concentration was used as primary exposure of the current study. Incident ICH from 2006 to 2015 was confirmed by review of medical records. RESULTS During 817 531 person-years of follow-up, we identified 755 incident ICH cases. The nadir risk of ICH was observed at fasting blood glucose concentration of 5.3 mmol/L. The adjusted hazard ratios and their 95% confidence intervals (CIs) of ICH were 1.59 (95% CI, 1.26-2.02) for diabetes mellitus or fasting blood glucose ≥7.00 mmol/L, 1.31 (95% CI, 1.02-1.69) for impaired fasting blood glucose (fasting blood glucose, 6.10-6.99 mmol/L), 0.98 (95% CI, 0.78-1.22) for fasting blood glucose 5.60 to 6.09 mmol/L, and 2.04 (95% CI, 1.23-3.38) for hypoglycemia (fasting blood glucose, <4.00 mmol/L), comparing with normal fasting blood glucose 4.00 to 5.59 mmol/L. The results persisted after excluding individuals who used hypoglycemic, aspirin, antihypertensive agents, or anticoagulants, and those with intracerebral hemorrhagic cases occurred in the first 2 years of follow-up. CONCLUSIONS In this large community-based cohort, low (<4.0 mmol/L) and high (≥6.1 mmol/L) fasting blood glucose concentrations were associated with higher risk of incident ICH, relative to fasting blood glucose concentrations of 4.00 to 6.09 mmol/L.
Jin, Cheng Li, Guohong Rexrode, Kathryn M Gurol, Mahmut E Yuan, Xiaodong Hui, Ying Ruan, Chunyu Vaidya, Anand Wang, Yanxiu Wu, Shouling Gao, Xiang
Diagnosis; Prognosis
Cardiovascular, Diabetes
May
01
Racial and Ethnic Disparities in Hospital Mortality among Ischemic Stroke Patients in Hawaii.
Abstract
BACKGROUND We evaluated disparities in in-hospital mortality rates among whites, Native Hawaiians and other Pacific Islanders (NHOPI), Filipinos, and other Asian groups in Hawaii who were hospitalized for acute ischemic stroke. MATERIALS AND METHODS Using a statewide hospital claims database, we performed a retrospective study including sequential acute ischemic stroke patients between 2010 and 2015. We compared in-hospital mortality rates among whites, NHOPI, Filipinos, other Asian groups excluding Filipinos, and other races (Blacks, Hispanics, Native Americans, mixed race). RESULTS A total of 13,030 patient discharges were included in this study. The mean (±SD) age in years at the time of stroke was 63.5 ± 14.3 for NHOPI, 69.6 ± 14.4 for Filipinos, 67.8 ± 14.2 for other race, 71.4 ± 13.8 for whites, and 76.1 ± 13.5 for other Asians (P < .001). NHOPI patients had higher rates of diabetes (48.8%), obesity (18.4%), and tobacco use (31.3%) compared with patients in other racial-ethnic categories. Filipino patients had the highest rate of hemorrhagic transformation (9.7%). Age-adjusted stroke mortality rates were highest among Filipinos (15.9%; 95% confidence interval [CI] = 14.3%-17.6%), followed by other Asian groups (15.1%; 95% CI = 14.0%-16.2%), NHOPI (14.8%; 95% CI = 12.8%-16.8%), other race (14.4%; 95% CI = 11.3%-17.4%), and lowest among whites (12.8%; 11.5%-14.2%). After adjusting for other confounding variables, Filipinos had higher mortality (odds ratio = 1.22, 95% CI = 1.03-1.45), whereas other Asian groups, NHOPI, and other race patients had mortality rates that were similar to whites. CONCLUSION In Hawaii, Filipino ethnicity is an independent risk factor for higher in-hospital stroke mortality compared with whites.
Ideta, Trevor R Lim, Eunjung Nakagawa, Kazuma Koenig, Matthew A
Diagnosis; Prognosis
Cardiovascular
May
12
Risk of chronic kidney disease in young adults with impaired glucose tolerance/impaired fasting glucose: a retrospective cohort study using electronic primary care records.
Abstract
BACKGROUND The risk of chronic kidney disease (CKD) is known to be elevated in patients with diabetes mellitus but the risk of young adults aged 18 to 40 years with impaired glucose tolerance/impaired fasting glucose (IGT/IFG) developing CKD is not well characterised. Furthermore, progression of IGT/IFG to diabetes and subsequent CKD development is not well understood. METHODS A retrospective cohort study was undertaken using The Health Improvement Network (THIN) database, a large dataset of electronic patient records. THIN database is jointly managed by IMS Health Real World Evidence Solution ( http://www.epic-uk.org/index.html ) and In Practice System (InPs). Cases were aged 18 to 40, with a diagnosis of IGT/IFG and registered at a practice contributing to THIN between 2000 and 2015. The study population consisted of 40,092 patients, including 21,454 (53.5%) female and 18,638 (46.5%) male. The median follow-up was approximately 2 years. The outcome was a diagnosis of CKD determined from either clinical coding or laboratory results. For the primary analysis the unadjusted and adjusted relative risk of CKD in IGT/IFG was compared to age, sex and practice matched controls with normoglycaemia. For the secondary analysis we compared the incidence of CKD before to after a diagnosis of type 2 diabetes (T2DM) in the IGT/IFG study cohort. RESULTS The Incidence Rate Ratio (IRR) for CKD for IGT/IFG compared to normoglycaemia was 4.0 [95% confidence interval (CI), 3.2 to 5.1, P < 0.001]. The adjusted IRR was 2.6 [95% CI, 2.0 to 3.4, P < 0.001]. The unadjusted IRR was 8.8 [95% CI, 7.7 to 10.0, P < 0.001] after IGT/IFG patients had developed T2DM and the adjusted IRR was 6.3 [95% CI, 5.5 to 7.2, P < 0.001]. CONCLUSION Our results show that young IGT/IFG subjects are also at higher risk of developing CKD. This risk is modulated by the degree of baseline renal function and glucose tolerance, being higher in those developing T2DM.
Jadhakhan, Ferozkhan Marshall, Tom Ryan, Ronan Gill, Paramjit
Diagnosis; Prognosis
Kidney disease
May
15
Relation between HbA and incident cardiovascular disease over a period of 6 years in the Hong Kong population.
Abstract
AIM The current trend on diabetes management advocates replacing the paradigm from a uniform to an individualized patient-centered haemoglobin A (HbA) target, but there is no consensus on the optimal HbA level. The study aimed at examining the association between HbA and the risk of cardiovascular diseases (CVD) for diabetic patients with different characteristics, in order to identify patient-centered treatment targets. METHODS A retrospective cohort study was conducted on 115,782 Chinese adult primary care patients with type 2 diabetes mellitus (DM) but no known CVD history, who were prescribed antidiabetic medications in 2010-2011. The cumulative mean HbA over a median follow-up period of 5.8 years was used to evaluate the relationship between HbA and CVD incidence using Cox analysis. Subgroup analyses were conducted by stratifying different baseline characteristics including gender, age, smoking status, diabetes duration, body mass index, Charlson's comorbidity index and DM treatment modalities. RESULTS For patients with a DM duration of<2years, an exponential relationship between HbA and risk of CVD was identified, suggesting that there was no threshold HbA level for CVD risk. For other diabetic patients, an HbA level of 6.8-7.2% was associated with a minimum risk for CVD and a J-shaped curvilinear association between HbA. The risk of CVD increased in patients with HbA<6.5% or ≥7.5%. CONCLUSION Among Chinese primary care patients at the early (<2years) disease stage, lower HbA targets (<6.5%) may be warranted to prevent CVD events whilst for all others, excessively lower HbA levels may not necessarily better and can potentially be harmful.
Wan, E Y F Yu, E Y T Fung, C S C Chin, W Y Fong, D Y T Chan, A K C Lam, C L K
Diagnosis; Prognosis
Cardiovascular, Diabetes, Kidney disease
Apr
24
Ethnic Differences in the Prevalence and Risk Factors of Diabetic Retinopathy: The Singapore Epidemiology of Eye Diseases Study.
Abstract
PURPOSE To evaluate the prevalence and risk factors for diabetic retinopathy (DR) in the Singapore Epidemiology of Eye Diseases (SEED) Study. DESIGN Population-based, cross-sectional study. PARTICIPANTS Persons of Malay, Indian, and Chinese ethnicity aged 40+ years, living in Singapore. METHODS Diabetes was defined as nonfasting plasma glucose ≥200 mg/dl (11.1 mmol/l), glycated hemoglobin A1c (HbA1c) >6.5%, self-reported physician-diagnosed diabetes, or the use of glucose-lowering medication. Retinal photographs, were graded for the presence and severity of DR using the modified Airlie House classification system. MAIN OUTCOME MEASURES Diabetic retinopathy, diabetic macular edema (DME), vision-threatening diabetic retinopathy (VTDR), defined as the presence of severe nonproliferative or proliferative DR, or clinically significant macular edema (CSME). RESULTS Of the 10 033 subjects, 2877 (28.7%) had diabetes and gradable photographs for analysis. The overall age-standardized prevalence (95% confidence interval [CI]) was 28.2% (25.9-30.6) for any DR, 7.6% (6.5-9.0) for DME, and 7.7% (6.6-9.0) for VTDR. Indians had a higher prevalence of any DR (30.7% vs. 26.2% in Chinese and 25.5% in Malays, P = 0.012); a similar trend was noted for any DME (P = 0.001) and CSME (P = 0.032). Independent risk factors for any DR were Indian ethnicity (odds ratio [OR], 1.41; 95% CI, 1.09-1.83, vs. Chinese), diabetes duration (OR, 1.10; 95% CI, 1.08-1.11, per year), HbA1c (OR, 1.25; 95% CI, 1.18-1.32, per %), serum glucose (OR, 1.03; 95% CI, 1.00-1.06, per mmol/l), and systolic blood pressure (OR, 1.14; 95% CI, 1.09-1.19, per 10 mmHg). Diastolic blood pressure (OR, 0.74; 95% CI, 0.65-0.84, per 10 mmHg increase), total cholesterol (OR, 0.87; 95% CI, 0.80-0.95, per mmol/l increase), and low-density lipoprotein (LDL) cholesterol (OR, 0.83; 95% CI, 0.74-0.92, per mmol/l increase) were associated with lower odds of any DR. Risk factors were largely similar across the 3 ethnic groups. CONCLUSIONS Indian Singaporeans have a higher prevalence of DR and DME compared with Chinese and Malays. Major risk factors for DR in this study were similar across the 3 ethnic groups. Addressing these risk factors may reduce the impact of DR in Asia, regardless of ethnicity.
Tan, Gavin S Gan, Alfred Sabanayagam, Charumathi Tham, Yih Chung Neelam, Kumari Mitchell, Paul Wang, Jie Jin Lamoureux, Ecosse L Cheng, Ching-Yu Wong, Tien Y
Prevalence
Diabetes
Apr
17
Risk of recurrent severe hypoglycemia remains associated with a past history of severe hypoglycemia up to 4 years: Results from a large prospective contemporary pediatric cohort of the DPV initiative.
Abstract
OBJECTIVES In a contemporary cohort of youth with type 1 diabetes, we examined the interval between episodes of severe hypoglycemia (SH) as a risk factor for recurrent SH or hypoglycemic coma (HC). METHODS This was a large longitudinal observational study. Using the DPV Diabetes Prospective follow-up data, we analyzed frequency and timing of recurrent SH (defined as requiring assistance from another person) and HC (loss of consciousness or seizures) in 14 177 youths with type 1 diabetes aged <20 years and at least 5 years of follow-up. RESULTS Among 14 177 patients with type 1 diabetes, 72% (90%) had no, 14% (6.8%) had 1 and 14% (3.2%) >1 SH (HC). SH or HC in the last year of observation was highest with SH in the previous year (odds ratio [OR] 4.7 [CI 4.0-5.5]/4.6 [CI 3.6-6.0]), but remained elevated even 4 years after an episode (OR 2.0 [CI 1.6-2.7]/2.2 [CI 1.5-3.1]). The proportion of patients who experienced SH or HC during the last year of observation was highest with SH/HC recorded during the previous year (23% for SH and 13% for HC) and lowest in those with no event (4.6% for SH and 2% for HC) in the initial 4 years of observation. CONCLUSIONS Even 4 years after an episode of SH/HC, risk for SH/HC remains higher compared to children who never experienced SH/HC. Clinicians should continue to regularly track hypoglycemia history at every visit, adjust diabetes education and therapy in order to avoid recurrences.
Pacaud, D Hermann, J M Karges, B Rosenbauer, J Danne, T Dürr, R Herbst, A Lindauer, S Müther, S Pötzsch, S Raile, K Witsch, M Holl, R W ,
Diagnosis; Prognosis
Diabetes
Apr
11
Social deprivation modifies the association between incident foot ulceration and mortality in type 1 and type 2 diabetes: a longitudinal study of a primary-care cohort.
Abstract
AIMS/HYPOTHESIS The aim of this study was to determine whether social deprivation in the presence of diabetes is an independent predictor of developing a foot ulcer and separately of mortality. METHODS This was a primary-care-based retrospective analysis of 13,955 adults with type 1 (n = 1370) or type 2 (n = 12,585) diabetes after a median follow-up of 10.5 years. Demographic characteristics, indices of social deprivation and clinical variables were assessed at baseline. The primary outcomes were new foot ulceration (in those without a previous history of foot ulcers) and all-cause mortality. Cox proportional hazard models were used to describe the associations among foot ulceration, social deprivation and mortality. RESULTS The mean age of the population was 69.4 (range: 16-89) years. The incidence of foot ulceration was greater in individuals with type 2 (8.6%) compared with type 1 diabetes (4.8%). Occurrence was similar by sex, but increased with age and deprivation index. Individuals in the highest quintile of deprivation were 77% more likely to develop a foot ulcer compared with those in the lowest quintile (OR 1.77 [95% CI 1.45, 2.14], p < 0.0001). Overall, 2946 (21.1%) deaths were recorded. Compared with individuals without a foot ulcer, the development of a foot ulcer was associated with a higher age- and sex-adjusted mortality rate (25.9% vs 14.0%), and a 72% (HR 1.72 [95% CI 1.56, 1.90], p < 0.001) increased risk of mortality in those with type 2 diabetes. Risk of death increased by 14% per quintile of deprivation in a univariable analysis (HR 1.14 [95% CI 1.10, 1.17]). In multivariable Cox regression analyses, there was a 48% increased risk of mortality in individuals with a foot ulcer (HR 1.48 [95% CI 1.33, 1.66]) independent of the Townsend index score (HR 1.13 [95% CI 1.10, 1.17], per quintile), baseline age, sex, diabetes type, smoking status, hypertension, statin use, β-blocker use, metformin use, HbAlevels and insulin use. CONCLUSIONS/INTERPRETATION This study confirms the high mortality rate in individuals with diabetes-related foot ulcers. In addition, socioeconomic disadvantage was found to be an independent effect modifier, contributing to an increased burden of mortality in people with diabetes who develop foot ulceration. In light of this, and as diabetes service configurations are orientated for the next 5-10 years, modelling of foot ulceration risk needs to take socioeconomic disadvantage into account.
Anderson, Simon G Shoo, Haika Saluja, Sushant Anderson, Christian D Khan, Adnan Livingston, Mark Jude, Edward B Lunt, Mark Dunn, George Heald, Adrian H
Causes and Prevention
Diabetes
Apr
11
Acute kidney injury impact on inpatient mortality in Clostridium difficile infection: A national propensity-matched study.
Abstract
BACKGROUND AND AIM Acute kidney injury (AKI) is used as a marker of severity in Clostridium difficile infection (CDI) patients. We estimated the true effect of AKI in inpatient mortality of CDI patients, as there are no large-scale, population-based, propensity-matched studies evaluating AKI's effect in this patient cohort. METHODS A retrospective observational study utilizing the National Inpatient Sample from years 2003 to 2012, including all adults with CDI, excluding cases missing data on age, inpatient mortality or gender. Trends and CDI-related complications as mortality predictors were assessed using survey-weighted multivariable regression. We estimated AKI's independent effect by propensity-matching, post-stratifying by chronic kidney disease status, allowing for multiple comorbidity adjustment. RESULTS A total of 2 859 599 patients with CDI were included, of which 896 122 (31.3%) had principal diagnosis of CDI. AKI prevalence was 22%. Mortality rate was 8.4%, while among AKI patients was higher (18.2%). In multivariable regression, AKI was associated with higher mortality (odds ratio [OR] = 3.16, 95% confidence interval [CI]: 3.02-3.30; P < 0.001), while after propensity matching, AKI increased mortality by 86% (OR = 1.86, 95% CI: 1.79-1.94; P < 0.001). CDI incidence increased by 1.8, together with the rate of AKI (12.6% in 2003 to 28.8% in 2012, P-trend < 0.001). Despite increasing hospitalizations, mortality over the study period decreased to 7.2% (2012) from 9.0% (2003); P-trend < 0.001. CONCLUSION Hospital admissions of patients with CDI and concomitant AKI are increasing, but their inpatient mortality has improved over the study period. AKI is a significant contributor to mortality, independently of other comorbidities, complications, and hospital characteristics, emphasizing the need for early diagnosis and aggressive management in such patients.
Charilaou, Paris Devani, Kalpit John, Febin Kanna, Sowjanya Ahlawat, Sushil Young, Mark Khanna, Sahil Reddy, Chakradhar
Diagnosis; Prognosis
Diabetes
Apr
10
Sex Differences in Treatments, Relative Survival, and Excess Mortality Following Acute Myocardial Infarction: National Cohort Study Using the SWEDEHEART Registry.
Abstract
BACKGROUND This study assessed sex differences in treatments, all-cause mortality, relative survival, and excess mortality following acute myocardial infarction. METHODS AND RESULTS A population-based cohort of all hospitals providing acute myocardial infarction care in Sweden (SWEDEHEART [Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies]) from 2003 to 2013 was included in the analysis. Excess mortality rate ratios (EMRRs), adjusted for clinical characteristics and guideline-indicated treatments after matching by age, sex, and year to background mortality data, were estimated. Although there were no sex differences in all-cause mortality adjusted for age, year of hospitalization, and comorbidities for ST-segment-elevation myocardial infarction (STEMI) and non-STEMI at 1 year (mortality rate ratio: 1.01 [95% confidence interval (CI), 0.96-1.05] and 0.97 [95% CI, 0.95-0.99], respectively) and 5 years (mortality rate ratio: 1.03 [95% CI, 0.99-1.07] and 0.97 [95% CI, 0.95-0.99], respectively), excess mortality was higher among women compared with men for STEMI and non-STEMI at 1 year (EMRR: 1.89 [95% CI, 1.66-2.16] and 1.20 [95% CI, 1.16-1.24], respectively) and 5 years (EMRR: 1.60 [95% CI, 1.48-1.72] and 1.26 [95% CI, 1.21-1.32], respectively). After further adjustment for the use of guideline-indicated treatments, excess mortality among women with non-STEMI was not significant at 1 year (EMRR: 1.01 [95% CI, 0.97-1.04]) and slightly higher at 5 years (EMRR: 1.07 [95% CI, 1.02-1.12]). For STEMI, adjustment for treatments attenuated the excess mortality for women at 1 year (EMRR: 1.43 [95% CI, 1.26-1.62]) and 5 years (EMRR: 1.31 [95% CI, 1.19-1.43]). CONCLUSIONS Women with acute myocardial infarction did not have statistically different all-cause mortality, but had higher excess mortality compared with men that was attenuated after adjustment for the use of guideline-indicated treatments. This suggests that improved adherence to guideline recommendations for the treatment of acute myocardial infarction may reduce premature cardiovascular death among women.
Alabas, Oras A Gale, Chris P Hall, Marlous Rutherford, Mark J Szummer, Karolina Lawesson, Sofia Sederholm Alfredsson, Joakim Lindahl, Bertil Jernberg, Tomas
Treatment / Management
Cardiovascular
Apr
10
Association of Hemoglobin Concentration and Its Change With Cardiovascular and All-Cause Mortality.
Abstract
BACKGROUND Anemia is thought to increase mortality risks, but the effects of high hemoglobin concentration on survival are unclear. The effect of change in hemoglobin concentrations on survival in the general population is also unknown. This study aimed to examine the effect of hemoglobin concentrations and their changes on cardiovascular and all-cause mortality risks. METHODS AND RESULTS We retrospectively analyzed a cohort from the NHIS-HEALS (National Health Insurance Service-National Health Screening Cohort) database, including 170 078 men and 122 116 women without cardiovascular diseases, aged >40 years at baseline, with hemoglobin concentrations available for both first and second health examinations. We assessed 2 independent variables: "One-time" hemoglobin concentrations and changes in hemoglobin from first to second examination. Participants were followed up for a median of 8 years to determine mortality related to myocardial infarction, stroke, all cardiovascular diseases, and all causes. Hemoglobin concentrations showed a U- or J-shaped association with cardiovascular and all-cause mortality after adjusting for cardiovascular risk factors. When anemic men achieved normal hemoglobin concentrations, the all-cause mortality risk decreased, with an adjusted hazard ratio of 0.67 (95% confidence interval, 0.59-0.77), in comparison with those whose anemia persisted. Both increases and decreases of hemoglobin concentration outside the normal range elevated all-cause mortality risk (adjusted hazard ratio: 1.39 [95% confidence interval, 1.28-1.49] and 1.10 [95% confidence interval, 1.01-1.20], respectively), compared with persistent normal hemoglobin concentrations. The trend was similar in women but was less significant. CONCLUSIONS Low or high hemoglobin concentrations were associated with elevated cardiovascular and all-cause mortality. Reaching and maintaining hemoglobin concentrations within the normal range correlated with decreased all-cause mortality.
Lee, Gyeongsil Choi, Seulggie Kim, Kyuwoong Yun, Jae-Moon Son, Joung Sik Jeong, Su-Min Kim, Sung Min Park, Sang Min
Diagnosis; Prognosis
Cardiovascular
Apr
10
Anesthetic type and hospital outcomes after carotid endarterectomy from the Vascular Quality Initiative database
Abstract
OBJECTIVE Studies on the safety of carotid endarterectomy (CEA) under different anesthetic techniques are sometimes contradictory. The aim of this study was to compare real-world outcomes of CEA under general anesthesia (GA) vs regional or local anesthesia (RA/LA). METHODS A retrospective analysis of the Vascular Quality Initiative database (2003-2017) was performed. Primary outcomes included perioperative stroke, death, and myocardial infarction (MI) occurring during the hospital stay. Univariate and multivariate analyses were used. To minimize selection bias and to evaluate comparable groups, patients were matched on baseline variables using coarsened exact matching. RESULTS Of 75,319 CEA cases, 6684 (8.9%) were performed under RA/LA. These patients were more likely to be older (median age, 72 vs 71 years) and male (62.5% vs 60.2%), with higher American Society of Anesthesiologists class (class 3-5, 94.2% vs 93.0%) than those undergoing CEA-GA (all P < .001). CEA-GA had higher crude rates of in-hospital cardiac outcomes including MI mainly diagnosed clinically or on electrocardiography (0.5% vs 0.2%; P = .01), dysrhythmia (1.6% vs 1.2%; P < .001), acute congestive heart failure (CHF; 0.5% vs 0.2%; P < .001), and hemodynamic instability (27.0% vs 20.0%; P < .001) compared with CEA-RA/LA. No difference in perioperative stroke or death was seen between the two groups. On multivariate analysis, CEA-GA was associated with twice the odds of in-hospital MI (adjusted odds ratio [aOR], 1.95; 95% confidence interval [CI], 1.06-3.59; P = .03), 4 times the odds of acute CHF (aOR, 3.92; 95% CI, 1.84-8.34; P < .001), and 1.5 times the odds of hemodynamic instability (aOR, 1.54; 95% CI, 1.44-1.66; P < .001). Patients undergoing CEA-GA had 1.8 times the odds of staying in the hospital for >1 day (aOR, 1.80; 95% CI, 1.67-1.93; P < .001). Coarsened exact matching confirmed our results. Risk factors associated with increased cardiac complications (MI and CHF) under GA included female gender, increased age, Medicaid insurance, history of smoking, medical comorbidities (such as hypertension, diabetes, coronary artery disease, and CHF), prior ipsilateral carotid intervention, and urgent/emergent procedures. CONCLUSIONS Patients undergoing CEA under GA have higher odds of postoperative MI, acute CHF, and hemodynamic instability compared with those undergoing CEA under RA/LA. They are also more likely to stay in the hospital for >1 day. However, the overall risk of cardiac adverse events after CEA was low, which made the differences clinically irrelevant. The choice of anesthesia approach to CEA should be driven by the team's experience and the patient's risk factors and preference.
Dakour Aridi, Hanaa Paracha, Nawar Nejim, Besma Locham, Satinderjit Malas, Mahmoud B
Treatment / Management
Cardiovascular
Apr
10
Increased risk of ischemic heart disease, hypertension, and type 2 diabetes in women with previous gestational diabetes mellitus, a target group in general practice for preventive interventions: A population-based cohort study.
Abstract
BACKGROUND Gestational diabetes mellitus (GDM) is associated with developing type 2 diabetes, but very few studies have examined its effect on developing cardiovascular disease. METHODS AND FINDINGS We conducted a retrospective cohort study utilizing a large primary care database in the United Kingdom. From 1 February 1990 to 15 May 2016, 9,118 women diagnosed with GDM were identified and randomly matched with 37,281 control women by age and timing of pregnancy (up to 3 months). Adjusted incidence rate ratios (IRRs) with 95% confidence intervals (CIs) were calculated for cardiovascular risk factors and cardiovascular disease. Women with GDM were more likely to develop type 2 diabetes (IRR = 21.96; 95% CI 18.31-26.34) and hypertension (IRR = 1.85; 95% CI 1.59-2.16) after adjusting for age, Townsend (deprivation) quintile, body mass index, and smoking. For ischemic heart disease (IHD), the IRR was 2.78 (95% CI 1.37-5.66), and for cerebrovascular disease 0.95 (95% CI 0.51-1.77; p-value = 0.87), after adjusting for the above covariates and lipid-lowering medication and hypertension at baseline. Follow-up screening for type 2 diabetes and cardiovascular risk factors was poor. Limitations include potential selective documentation of severe GDM for women in primary care, higher surveillance for outcomes in women diagnosed with GDM than control women, and a short median follow-up postpartum period, with a small number of outcomes for IHD and cerebrovascular disease. CONCLUSIONS Women diagnosed with GDM were at very high risk of developing type 2 diabetes and had a significantly increased incidence of hypertension and IHD. Identifying this group of women in general practice and targeting cardiovascular risk factors could improve long-term outcomes.
Daly, Barbara Toulis, Konstantinos A Thomas, Neil Gokhale, Krishna Martin, James Webber, Jonathan Keerthy, Deepi Jolly, Kate Saravanan, Ponnusamy Nirantharakumar, Krishnarajah
Causes and Prevention
Diabetes
Apr
10
Resting heart rate, temporal changes in resting heart rate, and overall and cause-specific mortality.
Abstract
OBJECTIVE Most studies investigating the association between resting heart rate (RHR) and mortality have focused on cardiovascular disease (CVD) mortality, and measured RHR at only one time point. We aimed to assess associations of RHR and changes in RHR over approximately a decade with overall and cause-specific mortality. METHODS We used data from participants in the Melbourne Collaborative Cohort Study with RHR measures at baseline (1990-1994; n=41 386; 9846 deaths) and at follow-up (2003-2007; n=21 692; 2818 deaths). RHR measures were taken by trained staff, using Dinamap monitors. Cox models were used to estimate HR and 95% CI for the associations between RHR and mortality. Vital status and cause of death were ascertained until August 2015 and December 2013, respectively. RESULTS After adjustment for confounders, including blood pressure and known medical conditions but not arrhythmias or atrial fibrillation, RHR was associated with a higher risk of death of similar magnitude for CVD (HR per 10 beats per minute (bpm)=1.11, 95% CI 1.07 to 1.16), cancer (HR=1.10, 95% CI 1.06 to 1.13) and other causes (HR=1.20, 95% CI 1.16 to 1.25). Higher mortality was observed for most cancer sites, including breast (HR=1.16, 95% CI 1.03 to 1.31), colorectal (HR=1.18, 95% CI 1.08 to 1.29), kidney (HR=1.27, 95% CI 1.03 to 1.57) and lung cancer (HR=1.19, 95% CI 1.10 to 1.29). Temporal increases in RHR were associated with higher mortality, particularly for individuals whose RHR increased by more than 15 bpm. CONCLUSIONS RHR and changes in RHR over a decade are associated with mortality risk, including from causes other than CVD such as breast, colorectal or lung cancer. Monitoring of RHR may have utility in identifying individuals at higher mortality risk.
Seviiri, Mathias Lynch, Brigid M Hodge, Allison M Yang, Yi Liew, Danny English, Dallas R Giles, Graham G Milne, Roger L Dugué, Pierre-Antoine
Causes and Prevention
Cardiovascular
Apr
10
Migraine and risk of cardiovascular diseases: Danish population based matched cohort study.
Abstract
OBJECTIVE To examine the risks of myocardial infarction, stroke (ischaemic and haemorrhagic), peripheral artery disease, venous thromboembolism, atrial fibrillation or atrial flutter, and heart failure in patients with migraine and in a general population comparison cohort. DESIGN Nationwide, population based cohort study. SETTING All Danish hospitals and hospital outpatient clinics from 1995 to 2013. PARTICIPANTS 51 032 patients with migraine and 510 320 people from the general population matched on age, sex, and calendar year. MAIN OUTCOME MEASURES Comorbidity adjusted hazard ratios of cardiovascular outcomes based on Cox regression analysis. RESULTS Higher absolute risks were observed among patients with incident migraine than in the general population across most outcomes and follow-up periods. After 19 years of follow-up, the cumulative incidences per 1000 people for the migraine cohort compared with the general population were 2517 for myocardial infarction, 4525 for ischaemic stroke, 116 for haemorrhagic stroke, 1311 for peripheral artery disease, 2718 for venous thromboembolism, 4734 for atrial fibrillation or atrial flutter, and 1918 for heart failure. Correspondingly, migraine was positively associated with myocardial infarction (adjusted hazard ratio 1.49, 95% confidence interval 1.36 to 1.64), ischaemic stroke (2.26, 2.11 to 2.41), and haemorrhagic stroke (1.94, 1.68 to 2.23), as well as venous thromboembolism (1.59, 1.45 to 1.74) and atrial fibrillation or atrial flutter (1.25, 1.16 to 1.36). No meaningful association was found with peripheral artery disease (adjusted hazard ratio 1.12, 0.96 to 1.30) or heart failure (1.04, 0.93 to 1.16). The associations, particularly for stroke outcomes, were stronger during the short term (0-1 years) after diagnosis than the long term (up to 19 years), in patients with aura than in those without aura, and in women than in men. In a subcohort of patients, the associations persisted after additional multivariable adjustment for body mass index and smoking. CONCLUSIONS Migraine was associated with increased risks of myocardial infarction, ischaemic stroke, haemorrhagic stroke, venous thromboembolism, and atrial fibrillation or atrial flutter. Migraine may be an important risk factor for most cardiovascular diseases.
Adelborg, Kasper Szépligeti, Szimonetta Komjáthiné Holland-Bill, Louise Ehrenstein, Vera Horváth-Puhó, Erzsébet Henderson, Victor W Sørensen, Henrik Toft
Causes and Prevention
Cardiovascular
Apr
10
Migraine and subsequent chronic kidney disease risk: a nationwide population-based cohort study.
Abstract
OBJECTIVE We compared the incidence and risk of chronic kidney disease (CKD) between subjects with new-onset migraine and matched controls without migraine in this large-scale retrospective cohort study. DESIGN Population-based cohort study. SETTING 8880 subjects with migraine and 503 070 subjects without migraine were enrolled between January 1, 2000 and December 31, 2013, all diagnosed to be without kidney disease. All the participants were registered in the National Health Insurance Research Database. PARTICIPANTS Finally, data from 7156 subjects with migraine and 7156 propensity-score-matched control subjects were analysed. PRIMARY OUTCOME MEASURE We used Cox proportional hazards regression to estimate adjusted HRs for incident CKD; subgroup analyses were performed to assess the interactive effects of migraine with demographics, comorbidities and long-term medications. RESULTS The incidence of CKD was higher in the migraine group than in the control group. The risk of developing CKD was significantly higher in subjects with migraine than without migraine (P=0.031). Subjects with migraine aged <65 years (age 40-64 (adjusted HR (aHR) 1.35; 95% CI 1.05 to 1.73); age <40 (aHR 1.55; 95% CI 1.02 to 2.36)), with ≥1 comorbid diseases (1-2 diseases (aHR 1.30; 95% CI 1.01 to 1.68); ≥3 diseases (aHR 1.45; 95% CI 1.01 to 2.07)), and not receiving anti-migraine agents (aHR 1.26; 95% CI 1.04 to 1.54) were at a higher risk of developing CKD compared with the control subjects. The interaction between migraine and comorbidities was not significant; age, male gender and long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) were independent risk factors for CKD in subjects with migraine. CONCLUSION Migraine may be an independent risk factor for CKD. Young subjects with migraine, and those with comorbid conditions or without medical control, are likely to be at higher risk for CKD. Ageing, male sex and NSAIDs tend to have an association with CKD in subjects with migraine.
Weng, Shuo-Chun Wu, Chia-Lin Kor, Chew-Teng Chiu, Ping-Fang Wu, Ming-Ju Chang, Chia-Chu Tarng, Der-Cherng
Causes and Prevention
Kidney disease
Apr
10
Associations of Four Community Factors With Longitudinal Change in Hemoglobin ALevels in Patients With Type 2 Diabetes.
Abstract
OBJECTIVE To evaluate associations of community factors with glycated hemoglobin (HbA). RESEARCH DESIGN AND METHODS We identified patients with type 2 diabetes who had an HbA≥7.5% (58 mmol/mol) and subsequent HbAtesting within 90-270 days. We used mixed-effect models to assess whether treatment intensification (TI) and community domains (community socioeconomic deprivation [CSD], food availability, fitness assets, and utilitarian physical activity favorability [quartiled]) were associated with HbAchange over 6 and 24 months, controlling for demographics, HbA, BMI, and time with evidence of type 2 diabetes. We evaluated whether community domains modified associations of TI with HbAchange using cross product terms. RESULTS There were 15,308 patients with 69,818 elevated HbAmeasures. The average reduction in HbAover 6 months was 0.07% less in townships with a high level of CSD (third quartile versus the first). Reductions were 0.10% greater for HbAin townships with the best food availability (versus worst). HbAreductions were 0.17-0.19% greater in census tracts in the second and third quartiles of utilitarian physical activity favorability versus the first. The association of TI with 6-month HbAchange was weaker in townships and boroughs with the worst CSD (versus best) and in boroughs with the best fitness assets (versus worst). The association of TI with 24-month HbAchange was weaker in census tracts with the worst CSD (versus third quartile) and strongest in census tracts most favorable for utilitarian physical activity (versus worst). CONCLUSIONS Community domains were associated with HbAchange and blunted TI effectiveness.
Hirsch, Annemarie G Durden, T Elizabeth Nordberg, Cara Berger, Andrea Schwartz, Brian S
Diagnosis; Prognosis
Diabetes
Apr
10
Factors of importance to 30-day survival after in-hospital cardiac arrest in Sweden - A population-based register study of more than 18,000 cases.
Abstract
BACKGROUND AND OBJECTIVE In-hospital cardiac arrest (IHCA) constitutes a major contributor to cardiovascular mortality. The aim of the present study was to investigate factors of importance to 30-day survival after IHCA in Sweden. METHODS A retrospective register study based on the Swedish Register of Cardiopulmonary Resuscitation (SRCPR) 2006-2015. Sixty-six of 73 hospitals in Sweden participated. The inclusion criterion was a confirmed cardiac arrest in which resuscitation was attempted among patients aged >18years. RESULTS In all, 18,069 patients were included, 39% of whom were women. The median age was 75years. Thirty-day survival was 28.3%, 93% with a CPC score of 1-2. One-year survival was 25.0%. Overall IHCA incidence in Sweden was 1.7 per 1000 hospital admissions. Several factors were found to be associated with 30-day survival in a multivariable analysis. They included cardiac arrest (CA) at working days during the daytime (08-20) compared with weekends and night-time (20-08) (OR 1.51 95% CI 1.39-1.64), monitored CA (OR 2.18 95% CI 1.99-2.38), witnessed CA (OR 2.87 95% CI 2.48-3.32) and if the first recorded rhythm was ventricular fibrillation/tachycardia, especially in combination with myocardial ischemia/infarction as the assumed aetiology of the CA (OR for interaction 4.40 95% CI 3.54-5.46). CONCLUSION 30-day survival after IHCA is associated with the time of the event, the aetiology of the CA and the degree of monitoring and this should influence decisions regarding the appropriate level of monitoring and care.
Hessulf, Fredrik Karlsson, Thomas Lundgren, Peter Aune, Solveig Strömsöe, Annelie Södersved Källestedt, Marie-Louise Djärv, Therese Herlitz, Johan Engdahl, Johan
Diagnosis; Prognosis
Cardiovascular
Mar
07
Anesthetic type and hospital outcomes after carotid endarterectomy from the Vascular Quality Initiative database
Abstract
OBJECTIVE Studies on the safety of carotid endarterectomy (CEA) under different anesthetic techniques are sometimes contradictory. The aim of this study was to compare real-world outcomes of CEA under general anesthesia (GA) vs regional or local anesthesia (RA/LA). METHODS A retrospective analysis of the Vascular Quality Initiative database (2003-2017) was performed. Primary outcomes included perioperative stroke, death, and myocardial infarction (MI) occurring during the hospital stay. Univariate and multivariate analyses were used. To minimize selection bias and to evaluate comparable groups, patients were matched on baseline variables using coarsened exact matching. RESULTS Of 75,319 CEA cases, 6684 (8.9%) were performed under RA/LA. These patients were more likely to be older (median age, 72 vs 71 years) and male (62.5% vs 60.2%), with higher American Society of Anesthesiologists class (class 3-5, 94.2% vs 93.0%) than those undergoing CEA-GA (all P < .001). CEA-GA had higher crude rates of in-hospital cardiac outcomes including MI mainly diagnosed clinically or on electrocardiography (0.5% vs 0.2%; P = .01), dysrhythmia (1.6% vs 1.2%; P < .001), acute congestive heart failure (CHF; 0.5% vs 0.2%; P < .001), and hemodynamic instability (27.0% vs 20.0%; P < .001) compared with CEA-RA/LA. No difference in perioperative stroke or death was seen between the two groups. On multivariate analysis, CEA-GA was associated with twice the odds of in-hospital MI (adjusted odds ratio [aOR], 1.95; 95% confidence interval [CI], 1.06-3.59; P = .03), 4 times the odds of acute CHF (aOR, 3.92; 95% CI, 1.84-8.34; P < .001), and 1.5 times the odds of hemodynamic instability (aOR, 1.54; 95% CI, 1.44-1.66; P < .001). Patients undergoing CEA-GA had 1.8 times the odds of staying in the hospital for >1 day (aOR, 1.80; 95% CI, 1.67-1.93; P < .001). Coarsened exact matching confirmed our results. Risk factors associated with increased cardiac complications (MI and CHF) under GA included female gender, increased age, Medicaid insurance, history of smoking, medical comorbidities (such as hypertension, diabetes, coronary artery disease, and CHF), prior ipsilateral carotid intervention, and urgent/emergent procedures. CONCLUSIONS Patients undergoing CEA under GA have higher odds of postoperative MI, acute CHF, and hemodynamic instability compared with those undergoing CEA under RA/LA. They are also more likely to stay in the hospital for >1 day. However, the overall risk of cardiac adverse events after CEA was low, which made the differences clinically irrelevant. The choice of anesthesia approach to CEA should be driven by the team's experience and the patient's risk factors and preference.
Dakour Aridi, Hanaa Paracha, Nawar Nejim, Besma Locham, Satinderjit Malas, Mahmoud B
Treatment / Management
Cardiovascular