Does type 2 diabetes confer higher relative rates of cardiovascular events in women compared with men?
ABSTRACT: AIMS:To investigate whether diabetes confers higher relative rates of cardiovascular events in women compared with men using contemporary data, and whether these sex-differences depend on age. METHODS AND RESULTS:All Danish residents aged 40-89?years without a history major adverse cardiovascular events, including heart failure, as of 1 January 2012 until 31 December 2016 were categorized by diabetes-status and characterized by individual-level linkage of Danish nationwide administrative registers. We used Poisson regression to calculate overall and age-dependent incidence rates, incidence rate ratios, and women-to-men ratios for myocardial infarction, heart failure, ischaemic stroke, or cardiovascular death (MACE-HF). Among 218 549 (46% women) individuals with diabetes, the absolute rate of MACE-HF was higher in men than in women (24.9 vs. 19.9 per 1000 person-years). Corresponding absolute rates in men and women without diabetes were 10.1 vs. 7.0 per 1000 person-years. Comparing individuals with and without diabetes, women had higher relative rates of MACE-HF than men [2.8 (confidence interval, CI 2.9-2.9) in women vs. 2.5 (CI 2.4-2.5) in men] with a women-to-men ratio of 1.15 (CI 1.11-1.19, P?
Project description:Aspirin has been recommended for the prevention of major adverse cardiovascular events (MACE, composite of non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death) in diabetic patients without previous cardiovascular disease. However, recent meta-analyses have prompted re-evaluation of this practice. The study objective was to evaluate the relative and absolute benefits and harms of aspirin for the prevention of incident MACE in patients with diabetes.We performed a systematic review and meta-analysis on seven studies (N=11,618) reporting on the use of aspirin for the primary prevention of MACE in patients with diabetes. Two reviewers conducted a systematic search of electronic databases (MEDLINE, EMBASE, the Cochrane Library, and BIOSIS) and hand searched bibliographies and clinical trial registries. Reviewers extracted data in duplicate, evaluated the quality of the trials, and calculated pooled estimates.A total of 11,618 participants were included in the analysis. The overall risk ratio (RR) for MACE was 0.91 (95% confidence intervals, CI, 0.82-1.00) with little heterogeneity among trials (I2 0.0%). Secondary outcomes of interest included myocardial infarction (RR, 0.85; 95% CI, 0.66-1.10), stroke (RR, 0.84; 95% CI, 0.64-1.11), cardiovascular death (RR, 0.95; 95% CI, 0.71-1.27), and all-cause mortality (RR, 0.95; 95% CI, 0.85-1.06). There were higher rates of hemorrhagic and gastrointestinal events. In absolute terms, these relative risks indicate that for every 10,000 diabetic patients treated with aspirin, 109 MACE may be prevented at the expense of 19 major bleeding events (with the caveat that the relative risk for the latter is not statistically significant).The studies reviewed suggest that aspirin reduces the risk of MACE in patients with diabetes without cardiovascular disease, while also causing a trend toward higher rates of bleeding and gastrointestinal complications. These findings and our absolute benefit and risk calculations suggest that those with diabetes but without cardiovascular disease lie somewhere between primary and secondary prevention patients on the spectrum of benefit and risk. This underscores the importance of considering individual risk in clinical decision making regarding aspirin in those with diabetes.
Project description:Background In statin trials, men and women derived similar relative risk reductions in cardiovascular events per 39 mg/ dL low-density lipoprotein cholesterol ( LDL -C) reduction. We explored whether lower LDL -C levels and greater LDL -C percentage reductions than those achieved with statins are associated with reduced major adverse cardiovascular event ( MACE ) rates in women as well as men. Methods and Results Data pooled from 10 phase 3 ODYSSEY randomized trials (n=4983) comparing alirocumab with control (placebo/ezetimibe) were assessed for association between 39 mg/dL lower on-treatment LDL -C and percentage LDL -C change from baseline, and MACE risk by sex, using multivariable Cox regression. Mean baseline LDL -C was 135 mg/dL (women) and 121 mg/dL (men). Average on-treatment LDL -C levels with alirocumab, ezetimibe, and placebo were 71, 114, and 134 mg/dL, respectively, in women (n=1882) and 52, 93, and 122 mg/dL, respectively, in men (n=3090). Overall, 36.5% and 58.7% of women and men, respectively, achieved on-treatment LDL -C <50 mg/dL. Each 39 mg/dL lower LDL -C was associated with a 33% and 22% lower risk of MACE in women ( P=0.0209) and men ( P=0.0307), respectively, with no significant between-sex difference ( P for heterogeneity=0.4597). Results were similar when analyzed per 50% LDL -C reduction, 24% ( P=0.1094) and 29% ( P=0.0125) lower MACE risk in women and men, respectively ( P for heterogeneity=0.7499). Alirocumab was generally well tolerated in both sexes. Conclusions The present analysis reinforces the notion that both sexes derive a similar cardiovascular benefit from LDL -C lowering. Although women had slightly higher on-treatment LDL -C than men, both sexes showed a similar lower MACE risk with lower LDL -C.
Project description:Secondary prevention of cardiovascular disease (CVD) has improved immensely during the past decade but controversies persist on cardiovascular benefits among women with diabetes. We investigated 11-year trends in hospital admission rates for acute myocardial infarction (AMI), stroke, percutaneous coronary intervention (PCI), and coronary artery bypass graft (CABG) in people with and without diabetes by gender in England.We identified all hospital admissions for cardiovascular disease causes among people aged 17 years and above between 2004 and 2014 in England. We calculated diabetes-specific and non-diabetes-specific rates for study outcomes by gender. To assess temporal changes, we fitted negative binomial regression models.Diabetes-related admission rates remained unchanged for AMI (incidence rate ratio (IRR) 0.99 [95% CI 0.98-1.01]), increased for stroke by 2% (1.02 [1.01-1.03]) and PCI by 3% (1.03 [1.01-1.04]) and declined for CABG by 3% (0.97 [0.96-0.98]) annually. Trends did not differ significantly by diabetes status. Women with diabetes had significantly lower rates of AMI (IRR 0.46 [95% CI 0.40-0.53]) and stroke (0.73 [0.63-0.84]) compared with men with diabetes. However, gender differences in admission rates for AMI attenuated in diabetes compared with the non-diabetic group. While diabetes tripled admission rates for AMI in men (IRR 3.15 [95% CI 2.72-3.64]), it increased it by over fourfold among women (4.27 [3.78-4.93]). Furthermore, while the presence of diabetes was associated with a threefold increased rates for PCI and fivefold increased rates for CABG (IRR 3.14 [2.83-3.48] and 5.01 [4.59-5.05], respectively) in men, among women diabetes was associated with a 4.4-fold increased admission rates for PCI and 6.2-fold increased rates for CABG (4.37 [3.93-4.85] and 6.24 [5.66-6.88], respectively). Proportional changes in rates were similar in men and women for all study outcomes, leaving the relative risk of admissions unchanged.Diabetes still confers a greater increase in risk of hospital admission for AMI in women relative to men. However, the absolute risk remains higher in men. These results call for intensified CVD risk factor management among people with diabetes, consideration of gender-specific treatment targets and treatment intensity to be aligned with levels of CVD risk.
Project description:Our aims were to determine the pace of change in cardiovascular risk factors by age, gender and socioeconomic groups from 1994 to 2008, and quantify the magnitude, direction and change in absolute and relative inequalities.Time trend analysis was used to measure change in absolute and relative inequalities in risk factors by gender and age (16-54, ? 55 years), using repeated cross-sectional data from the Health Survey for England 1994-2008. Seven risk factors were examined: smoking, obesity, diabetes, high blood pressure, raised cholesterol, consumption of five or more daily portions of fruit and vegetables, and physical activity. Socioeconomic group was measured using the Index of Multiple Deprivation 2007.Between 1994 and 2008, the prevalence of smoking, high blood pressure and raised cholesterol decreased in most deprivation quintiles. However, obesity and diabetes increased. Increasing absolute inequalities were found in obesity in older men and women (p = 0.044 and p = 0.027 respectively), diabetes in young men and older women (p = 0.036 and p = 0.019 respectively), and physical activity in older women (p = 0.025). Relative inequality increased in high blood pressure in young women (p = 0.005). The prevalence of raised cholesterol showed widening absolute and relative inverse gradients from 1998 onwards in older men (p = 0.004 and p ? 0.001 respectively) and women (p ? 0.001 and p ? 0.001).Favourable trends in smoking, blood pressure and cholesterol are consistent with falling coronary heart disease death rates. However, adverse trends in obesity and diabetes are likely to counteract some of these gains. Furthermore, little progress over the last 15 years has been made towards reducing inequalities. Implementation of known effective population based approaches in combination with interventions targeted at individuals/subgroups with poorer cardiovascular risk profiles are therefore recommended to reduce social inequalities.
Project description:Atrial fibrillation (AF) is a strong risk factor for heart failure (HF); HF onset in patients with AF is associated with increased morbidity and mortality. Risk factors that predict HF in individuals with AF in the community are not well established.We examined clinical variables related to the 10-year incidence of HF in 725 individuals (mean 73.3 years, 45% women) with documented AF in the Framingham Heart Study. Event rates for incident HF (n = 161, 48% in women) were comparable in women (4.30 per 100 person-years) and men (3.34 per 100 person-years). Age, body mass index, ECG LV hypertrophy, diabetes, significant murmur, and history of myocardial infarction were positively associated with incident HF in multivariable models (C-statistic 0.71; 95% confidence interval 0.67-0.75). We developed a risk algorithm for estimating absolute risk of HF in AF patients with good model fit and calibration (adjusted calibration ?2 statistic 7.29; P(?2) = 0.61). Applying the algorithm, 47.6% of HF events occurred in the top tertile in men compared with 13.1% in the bottom tertile, and 58.4% in women in the upper tertile compared with 18.2% in the lowest category. For HF type, women had a non-significantly higher incidence of HF with preserved EF compared with men.We describe advancing age, LV hypertrophy, body mass index, diabetes, significant heart murmur, and history of myocardial infarction as clinical predictors of incident HF in individuals with AF. A risk algorithm may help identify individuals with AF at high risk of developing HF.
Project description:To determine whether an angiotensin-converting enzyme inhibitor (lisinopril) or calcium channel blocker (amlodipine) is superior to a diuretic (chlorthalidone) in reducing cardiovascular disease incidence in sex subgroups, we carried out a prespecified subgroup analysis of 15 638 women and 17 719 men in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Total follow-up (active treatment + passive surveillance using national administrative databases to ascertain deaths and hospitalizations) was 8 to 13 years. The primary outcome was fatal coronary heart disease or nonfatal myocardial infarction. Secondary outcomes included all-cause mortality, stroke, combined cardiovascular disease (coronary heart disease death, nonfatal myocardial infarction, stroke, angina, coronary revascularization, heart failure [HF], or peripheral vascular disease), and end-stage renal disease. In-trial rates of HF, stroke, and combined cardiovascular disease were significantly higher for lisinopril compared with chlorthalidone, and rates of HF were significantly higher for amlodipine compared with chlorthalidone in both men and women. There were no significant treatment sex interactions. These findings did not persist through the extension period with the exception of the HF result for amlodipine versus chlorthalidone, which did not differ significantly by sex. For both women and men, rates were not lower in the amlodipine or lisinopril groups than in the chlorthalidone group for either the primary coronary heart disease outcome or any other cardiovascular disease outcome, and chlorthalidone-based treatment resulted in the lowest risk of HF. Neither lisinopril nor amlodipine is superior to chlorthalidone for initial treatment of hypertension in either women or men. Clinical Trial Registration- clinicaltrials.gov; Identifier: NCT00000542.
Project description:Importance:Coronary computed tomographic angiography (coronary CTA) can characterize coronary artery disease, including high-risk plaque. A noninvasive method of identifying high-risk plaque before major adverse cardiovascular events (MACE) could provide practice-changing optimizations in coronary artery disease care. Objective:To determine whether high-risk plaque detected by coronary CTA was associated with incident MACE independently of significant stenosis (SS) and cardiovascular risk factors. Design, Setting, and Participants:This prespecified nested observational cohort study was part of the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial. All stable, symptomatic outpatients in this trial who required noninvasive cardiovascular testing and received coronary CTA were included and followed up for a median of 25 months. Exposures:Core laboratory assessment of coronary CTA for SS and high-risk plaque (eg, positive remodeling, low computed tomographic attenuation, or napkin-ring sign). Main Outcomes and Measures:The primary end point was an adjudicated composite of MACE (defined as death, myocardial infarction, or unstable angina). Results:The study included 4415 patients, of whom 2296 (52%) were women, with a mean age of 60.5 years, a median atherosclerotic cardiovascular disease (ASCVD) risk score of 11, and a MACE rate of 3% (131 events). A total of 676 patients (15.3%) had high-risk plaques, and 276 (6.3%) had SS. The presence of high-risk plaque was associated with a higher MACE rate (6.4% vs 2.4%; hazard ratio, 2.73; 95% CI, 1.89-3.93). This association persisted after adjustment for ASCVD risk score and SS (adjusted hazard ratio [aHR], 1.72; 95% CI, 1.13-2.62). Adding high-risk plaque to the ASCVD risk score and SS assessment led to a significant continuous net reclassification improvement (0.34; 95% CI, 0.02-0.51). Presence of high-risk plaque increased MACE risk among patients with nonobstructive coronary artery disease relative to patients without high-risk plaque (aHR, 4.31 vs 2.64; 95% CI, 2.25-8.26 vs 1.49-4.69). There were no significant differences in MACE in patients with SS and high-risk plaque as opposed to those with SS but not high-risk plaque (aHR, 8.68 vs. 9.31; 95% CI, 4.25-17.73 vs 4.21-20.61). High-risk plaque was a stronger predictor of MACE in women (aHR, 2.41; 95% CI, 1.25-4.64) vs men (aHR, 1.40; 95% CI, 0.81-2.39) and younger patients (aHR, 2.33; 95% CI, 1.20-4.51) vs older ones (aHR, 1.36; 95% CI, 0.77-2.39). Conclusions and Relevance:High-risk plaque found by coronary CTA was associated with a future MACE in a large US population of outpatients with stable chest pain. High-risk plaque may be an additional risk stratification tool, especially in patients with nonobstructive coronary artery disease, younger patients, and women. The importance of findings is limited by low absolute MACE rates and low positive predictive value of high-risk plaque. Trial Registration:clinicaltrials.gov Indentifier: NCT01174550.
Project description:By 2017 estimates, diabetes mellitus affects 425 million people globally; approximately 90-95% of these have type 2 diabetes. This narrative review highlights two domains of sex differences related to the burden of type 2 diabetes across the life span: sex differences in the prevalence and incidence of type 2 diabetes, and sex differences in the cardiovascular burden conferred by type 2 diabetes. In the presence of type 2 diabetes, the difference in the absolute rates of cardiovascular disease (CVD) between men and women lessens, albeit remaining higher in men. Large-scale observational studies suggest that type 2 diabetes confers 25-50% greater excess risk of incident CVD in women compared with men. Physiological and behavioural mechanisms that may underpin both the observed sex differences in the prevalence of type 2 diabetes and the associated cardiovascular burden are discussed in this review. Gender differences in social behavioural norms and disparities in provider-level treatment patterns are also highlighted, but not described in detail. We conclude by discussing research gaps in this area that are worthy of further investigation.
Project description:A prospective observational study was conducted to investigate the residual risk factors to predict recurrence of major adverse cardiovascular events (MACE) in atherosclerotic cardiovascular disease (ASCVD) patients with a high prevalence under lipid-lowering therapy, particularly in the subpopulations of diabetic and nondiabetic individuals. A total of 5,483 adults (with a mean age of 66.4 and 73.3% male) with established coronary heart disease, cerebrovascular disease, or peripheral artery disease were identified from the T-SPARCLE multi-center registry. Of them, 38.6% had diabetes. The residual risk factors for MACE are divergent in these atherosclerotic patients with and without diabetes. In diabetic subpopulation, the risk of MACE was significantly increased with heart failure (HF), chronic kidney disease (CKD) stage 4-5 (vs. stage 1-2), without beta blocker use, and higher non-HDL-C, after controlling for covariates including statin use and the intensity of therapy. Increased LDL-C and TG levels were also associated with increased risk, but to a much less extent. Among nondiabetic individuals, HF, CKD stage 4-5, and history of myocardial infarction were the significant independent predictors of MACE. It is suggested that ASCVD patients with concomitant diabetes need stricter control of lipid, particularly non-HDL-C levels, to reduce cardiovascular risk when on statin therapy.
Project description:This study sought to compared the use and effectiveness of bleeding avoidance strategies (BAS) by sex.Women have higher rates of bleeding following percutaneous coronary intervention (PCI).Among 570,777 men (67.5%) and women (32.5%) who underwent PCI in the National Cardiovascular Data Registry's CathPCI Registry between July 1, 2009 and March 31, 2011, in-hospital bleeding rates and the use of BAS (vascular closure devices, bivalirudin, radial approach, and their combinations) were assessed. The relative risk of bleeding for each BAS compared with no BAS was determined in women and men using multivariable logistic regressions adjusted for clinical characteristics and the propensity for receiving BAS. Finally, the absolute risk differences in bleeding associated with BAS were compared.Overall, the use of any BAS differed slightly between women and men (75.4% vs. 75.7%, p = 0.01). When BAS was not used, women had significantly higher rates of bleeding than men (12.5% vs. 6.2%, p < 0.01). Both sexes had similar adjusted risk reductions of bleeding when any BAS was used (women, odds ratio: 0.60, 95% confidence interval [CI]: 0.57 to 0.63; men, odds ratio: 0.62, 95% CI: 0.59 to 0.65). Women and men had lower absolute bleeding risks with BAS; however, these absolute risk differences were greater in women (6.3% vs. 3.2%, p < 0.01).Women continue to have almost twice the rate of bleeding following PCI. The use of any BAS was associated with a similarly lower risk of bleeding for men and women; however, the absolute risk differences were substantially higher in women. These data underscore the importance of applying effective strategies to limit post-PCI bleeding, especially in women.