ObjeCtiveTo quantify the association between atrial fibrillation and cardiovascular disease, renal disease, and death.Design Systematic review and meta-analysis.
In observational studies, abdominal adiposity has been associated with type 2 diabetes and coronary heart disease (CHD). Whether these associations represent causal relationships remains uncertain.OBJECTIVE To test the association of a polygenic risk score for waist-to-hip ratio (WHR) adjusted for body mass index (BMI), a measure of abdominal adiposity, with type 2 diabetes and CHD through the potential intermediates of blood lipids, blood pressure, and glycemic phenotypes. DESIGN, SETTING, AND PARTICIPANTSA polygenic risk score for WHR adjusted for BMI, a measure of genetic predisposition to abdominal adiposity, was constructed with 48 single-nucleotide polymorphisms. The association of this score with cardiometabolic traits, type 2 diabetes, and CHD was tested in a mendelian randomization analysis that combined case-control and cross-sectional data sets. Estimates for cardiometabolic traits were based on a combined data set consisting of summary results from 4 genome-wide association studies conducted from 2007 to 2015, including up to 322 154 participants, as well as individual-level, cross-sectional data from the UK Biobank collected from 2007-2011, including 111 986 individuals. Estimates for type 2 diabetes and CHD were derived from summary statistics of 2 separate genome-wide association studies conducted from 2007 to 2015 and including 149 821 individuals and 184 305 individuals, respectively, combined with individual-level data from the UK Biobank.EXPOSURES Genetic predisposition to increased WHR adjusted for BMI. MAIN OUTCOMES AND MEASURES Type 2 diabetes and CHD.RESULTS Among 111 986 individuals in the UK Biobank, the mean age was 57 (SD, 8) years, 58 845 participants (52.5%) were women, and mean WHR was 0.875. Analysis of summary-level genome-wide association study results and individual-level UK Biobank data demonstrated that a 1-SD increase in WHR adjusted for BMI mediated by the polygenic risk score was associated with 27-mg/dL higher triglyceride levels, 4.1-mg/dL higher 2-hour glucose levels, and 2.1-mm Hg higher systolic blood pressure (each P < .001). A 1-SD genetic increase in WHR adjusted for BMI was also associated with a higher risk of type 2 diabetes (odds ratio, 1.77 [95% CI, 1.57-2.00]; absolute risk increase per 1000 participant-years, 6.0 [95% CI, CI, 4.4-7.8]; number of participants with type 2 diabetes outcome, 40 530) and CHD (odds ratio, 1.46 [95% CI,; absolute risk increase per 1000 participant-years, 1.8 [95% CI, 1.3-2.4]; number of participants with CHD outcome, 66 440).CONCLUSIONS AND RELEVANCE A genetic predisposition to higher waist-to-hip ratio adjusted for body mass index was associated with increased risk of type 2 diabetes and coronary heart disease. These results provide evidence supportive of a causal association between abdominal adiposity and these outcomes.
ObjeCtiveTo determine whether atrial fibrillation is a stronger risk factor for cardiovascular disease and death in women compared with men.
Whether anxiety is a risk factor for a range of cardiovascular diseases is unclear. We aimed to determine the association between anxiety and a range of cardiovascular diseases. MEDLINE and EMBASE were searched for cohort studies that included participants with and without anxiety, including subjects with anxiety, worry, posttraumatic stress disorder, phobic anxiety, and panic disorder. We examined the association of anxiety with cardiovascular mortality, major cardiovascular events (defined as the composite of cardiovascular death, stroke, coronary heart disease, and heart failure), stroke, coronary heart disease, heart failure, and atrial fibrillation. We identified 46 cohort studies containing 2,017,276 participants and 222,253 subjects with anxiety. Anxiety was associated with a significantly elevated risk of cardiovascular mortality (relative risk [RR] 1.41, CI 1.13 to 1.76), coronary heart disease (RR 1.41, CI 1.23 to 1.61), stroke (RR 1.71, CI 1.18 to 2.50), and heart failure (RR 1.35, CI 1.11 to 1.64). Anxiety was not significantly associated with major cardiovascular events or atrial fibrillation although CIs were wide. Phobic anxiety was associated with a higher risk of coronary heart disease than other anxiety disorders, and posttraumatic stress disorder was associated with a higher risk of stroke. Results were broadly consistent in sensitivity analyses. Anxiety disorders are associated with an elevated risk of a range of different cardiovascular events, including stroke, coronary heart disease, heart failure, and cardiovascular death. Whether these associations are causal is unclear.
Objectives To determine whether an association exists between the number of published randomised controlled trials and the global burden of disease, whether certain diseases are under-investigated relative to their burden, and whether the relation between the output of randomised trials and global burden of disease can be explained by the relative disease burden in high and low income regions. Design Cross sectional investigation. Study sample All primary reports of randomised trials published in December 2012 and indexed in PubMed by 17 November 2013. Main outcome measures Number of trials conducted and number of participants randomised for each of 239 different diseases or injuries; variation in each outcome explainable by total disability adjusted life years (a measure of the overall burden of each disease) and the ratio of disability adjusted life years in low income to high income regions (a measure of whether a disease is more likely to affect people living in high income regions) quantified using multivariable regression. Results 4190 abstracts were reviewed and 1351 primary randomised trials identified, of which 1097 could be classified using the global burden of disease taxonomy. Total disability adjusted life years was poorly associated with number of randomised trials and number of participants randomised in univariable analysis (Spearman’s r =0.35 and 0.33, respectively), although it was a significant predictor in the univariable and multivariable models (P<0.001). Diseases for which the burden was predominantly located in low income regions had sevenfold fewer trials per million disability adjusted life years than diseases predominantly located in high income regions. However, only 26% of the variation in number of trials among diseases could be explained by total disability adjusted life years and the ratio of disability adjusted life years in low income regions to high income regions. Many high income type diseases (for example, neck pain, glomerulonephritis) have proportionally fewer randomised trials compared with low income type diseases (for example, vitamin A deficiency). Conclusions Overall, a weak association existed between global burden of disease and number of published randomised trials. A global observatory for research is needed to monitor and reduce the discordance between the output of randomised trials and global burden of disease.
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