scholarly journals Sex Differences in the Risk of Coronary Heart Disease Associated With Type 2 Diabetes: A Mendelian Randomization Analysis

2020 ◽  
Author(s):  
Tricia M. Peters ◽  
Michael V. Holmes ◽  
J. Brent Richards ◽  
Tom Palmer ◽  
Vincenzo Forgetta ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Sensitivity Analyses ◽  
Chd Risk ◽  
Unit Increase

<b>Objective</b>: Observational studies have demonstrated that type 2 diabetes is a stronger risk factor for coronary heart disease (CHD) in women compared with men. However, it is not clear whether this reflects a sex differential in the causal effect of diabetes on CHD risk or results from sex-specific residual confounding. <p><b>Methods</b>: Using 270 single nucleotide polymorphisms (SNPs) for type 2 diabetes identified in a type 2 diabetes genome-wide association study, we performed a sex-stratified Mendelian randomization (MR) study of type 2 diabetes and CHD using individual participant data in UK Biobank (N=251,420 women and 212,049 men). Weighted-median, MR Egger, MR-PRESSO and radial MR from summary-level analyses were used for pleiotropy assessment. </p> <p><b>Results</b>: MR analyses showed that genetic risk of type 2 diabetes increased the odds of CHD for women (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.08-1.18 per 1-log unit increase in odds of type 2 diabetes) and men (OR 1.21, 95% CI 1.17-1.26 per 1-log unit increase in odds of type 2 diabetes). Sensitivity analyses showed some evidence of directional pleiotropy, however, results were similar after correction for outlier SNPs.</p> <p><b>Conclusions</b>: This MR analysis supports a causal effect of genetic liability to type 2 diabetes on risk of CHD that is not stronger for women than men. Assuming a lack of bias, these findings suggest that the prevention and management of type 2 diabetes for CHD risk reduction is of equal priority in both sexes.</p>

scholarly journals Sex Differences in the Risk of Coronary Heart Disease Associated With Type 2 Diabetes: A Mendelian Randomization Analysis

2020 ◽  
Author(s):  
Tricia M. Peters ◽  
Michael V. Holmes ◽  
J. Brent Richards ◽  
Tom Palmer ◽  
Vincenzo Forgetta ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Sensitivity Analyses ◽  
Chd Risk ◽  
Unit Increase

<b>Objective</b>: Observational studies have demonstrated that type 2 diabetes is a stronger risk factor for coronary heart disease (CHD) in women compared with men. However, it is not clear whether this reflects a sex differential in the causal effect of diabetes on CHD risk or results from sex-specific residual confounding. <p><b>Methods</b>: Using 270 single nucleotide polymorphisms (SNPs) for type 2 diabetes identified in a type 2 diabetes genome-wide association study, we performed a sex-stratified Mendelian randomization (MR) study of type 2 diabetes and CHD using individual participant data in UK Biobank (N=251,420 women and 212,049 men). Weighted-median, MR Egger, MR-PRESSO and radial MR from summary-level analyses were used for pleiotropy assessment. </p> <p><b>Results</b>: MR analyses showed that genetic risk of type 2 diabetes increased the odds of CHD for women (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.08-1.18 per 1-log unit increase in odds of type 2 diabetes) and men (OR 1.21, 95% CI 1.17-1.26 per 1-log unit increase in odds of type 2 diabetes). Sensitivity analyses showed some evidence of directional pleiotropy, however, results were similar after correction for outlier SNPs.</p> <p><b>Conclusions</b>: This MR analysis supports a causal effect of genetic liability to type 2 diabetes on risk of CHD that is not stronger for women than men. Assuming a lack of bias, these findings suggest that the prevention and management of type 2 diabetes for CHD risk reduction is of equal priority in both sexes.</p>

scholarly journals Gender Differences in Risks of Coronary Heart Disease and Stroke in Patients with Type 2 Diabetes Mellitus and Their Association with Metabolic Syndrome in China

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Mei-Fang Yao ◽  
Jie He ◽  
Xue Sun ◽  
Xiao-Li Ji ◽  
Yue Ding ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Coronary Heart Disease ◽  
Type 2 Diabetes Mellitus ◽  
Heart Disease ◽  
Stroke Risk ◽  
Chinese Women ◽  
Chd Risk

Coronary heart disease (CHD) and stroke are common complications of type 2 diabetes mellitus (T2DM). We aimed to explore the differences in the risks of CHD and stroke between Chinese women and men with T2DM and their association with metabolic syndrome (MS). This study included 1514 patients with T2DM. The Asian Guidelines of ATPIII (2005) were used for MS diagnosis, and the UKPDS risk engine was used to evaluate the 10-year CHD and stroke risks. Women had lower CHD risk (15.3% versus 26.3%), fatal CHD risk (11.8% versus 19.0%), stroke risk (8.4% versus 10.3%), and fatal stroke risk (1.4% versus 1.6%) compared with men with T2DM (p<0.05–0.001). The CHD risk (28.4% versus 22.6%, p<0.001) was significantly higher in men with MS than in those without MS. The CHD (16.2% versus 11.0%, p<0.001) and stroke risks (8.9% versus 5.8%, p<0.001) were higher in women with MS than in those without MS. In conclusion, our findings indicated that Chinese women with T2DM are less susceptible to CHD and stroke than men. Further, MS increases the risk of both these events, highlighting the need for comprehensive metabolic control in T2DM.

Obesity and cardiovascular outcomes: another look at a meta-analysis of Mendelian randomization studies

2019 ◽  
Vol 68 (2) ◽  
pp. 357-363 ◽  
Author(s):  
George A Kelley ◽  
Kristi S Kelley ◽  
Brian L Stauffer
Keyword(s):  
Type 2 Diabetes ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Mendelian Randomization ◽  
Meta Analysis ◽  
Positive Association ◽  
Small Study ◽  
Point Estimates ◽  
Inverse Variance

This study used the inverse variance heterogeneity (IVhet) model to conduct a reanalysis of a recent meta-analysis that reported a positive association, based on the random-effects (RE) model, between obesity and the incidence of type 2 diabetes and coronary heart disease, but not all-cause stroke, in adults. Data emanated from a recent meta-analysis of five Mendelian randomization studies representing 881,692 adults. Results were pooled using the IVhet model and reported as OR’s and 95% CI. Small-study effects were examined using the Doi plot and Luis Furuya-Kanamori (LFK) index. Influence analysis was also conducted. The association between obesity and type 2 diabetes, coronary heart disease, and all-cause stroke was, respectively, 1.38 (95% CI 1.00 to 1.90, p=0.05, I2=93%), 1.10 (95% CI 0.90 to 1.35, p=0.35, I2=87%), and 1.02 (95% CI 0.95 to 1.09, p=0.64, I2=0%). Compared with the original RE model, results were similar for all-cause stroke, but point estimates for type 2 diabetes and coronary heart disease were smaller (29.3% and 9.8%) with wider (7.0% and 14.7%), overlapping CI. Major asymmetry suggestive of small-study effects was observed (LFK=3.59). With the exception of one study for type 2 diabetes, results remained uncertain (overlapping 95% CI) when each study was deleted from the model once. A lack of certainty exists regarding the association between obesity and the incidence of type 2 diabetes, coronary heart disease, and all-cause stroke in adults.

scholarly journals Prevalence and Risk Factors of Coronary Heart Disease in Chinese Patients with type 2 Diabetes Mellitus, 2013-2018

2020 ◽  
Author(s):  
Chenchen Wang ◽  
Zuoling Xie ◽  
Xi Huang ◽  
Zheng Wang ◽  
Haiyan Shangguan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Coronary Heart Disease ◽  
Regression Analysis ◽  
Heart Disease ◽  
Diabetic Patients ◽  
Population Census ◽  
Chd Risk ◽  
Chd Risk Factors

Abstract Background: Coronary heart disease (CHD) is the most common cause of death in patients with type 2 diabetes (T2DM). We aim to estimate the prevalence of CHD and cardiovascular risk factors in Chinese diabetic inpatients.Methods: A total of 66536 diabetic inpatients from 2013 to 2018 were investigated, demographic and clinical data were gathered from 30693 patients with T2DM. The age-standardized prevalence of CHD was calculated on the basis of data from Chinese population census in 2010. Multiple imputation was used to impute missing values and logistic regression analysis was used to analyze the risk factors.Results: The crude prevalence of CHD was estimated to be 23.5% and a standardized prevalence was 13.9% (16.0% in men and 11.9% in women). More than half of diabetic patients with CHD have 4 or above of the 5 traditional risk factors, which is much higher than 38.96% of diabetic patients (p<0.01). Multivariate regression analysis showed that diabetes duration, hypertension, smoking, underweight, overweight, obesity, hypoglycemia were significantly associated with a higher risk of CHD (all p<0.05). The odds ratio of CHD in patients having 3, 4, or 5 CHD risk factors were 2.35 (95%CI 1.81- 3.04), 2.96 (95%CI 2.28- 3.85), and 5.29 (95%CI 4.04- 6.93), compared with diabetes patients without any other risk factors.Conclusions: The prevalence of CHD was rather high in Chinese T2DM inpatients, aggregation of CHD risk factors was more seriously, hierarchical CHD prevention strategies based on risk factors are needed for them.

scholarly journals Rheumatoid Arthritis and Cardio-Cerebrovascular Disease: A Mendelian Randomization Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Shizheng Qiu ◽  
Meijie Li ◽  
Shunshan Jin ◽  
Haoyu Lu ◽  
Yang Hu
Keyword(s):  
Rheumatoid Arthritis ◽  
Cardiovascular Disease ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Cerebrovascular Disease ◽  
Heart Attack ◽  
Large Scale ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Sensitivity Analyses

Significant genetic association exists between rheumatoid arthritis (RA) and cardiovascular disease. The associated mechanisms include common inflammatory mediators, changes in lipoprotein composition and function, immune responses, etc. However, the causality of RA and vascular/heart problems remains unknown. Herein, we performed Mendelian randomization (MR) analysis using a large-scale RA genome-wide association study (GWAS) dataset (462,933 cases and 457,732 controls) and six cardio-cerebrovascular disease GWAS datasets, including age angina (461,880 cases and 447,052 controls), hypertension (461,880 cases and 337,653 controls), age heart attack (10,693 cases and 451,187 controls), abnormalities of heartbeat (461,880 cases and 361,194 controls), stroke (7,055 cases and 454,825 controls), and coronary heart disease (361,194 cases and 351,037 controls) from United Kingdom biobank. We further carried out heterogeneity and sensitivity analyses. We confirmed the causality of RA with age angina (OR = 1.17, 95% CI: 1.04–1.33, p = 1.07E−02), hypertension (OR = 1.45, 95% CI: 1.20–1.75, p = 9.64E−05), age heart attack (OR = 1.15, 95% CI: 1.05–1.26, p = 3.56E−03), abnormalities of heartbeat (OR = 1.07, 95% CI: 1.01–1.12, p = 1.49E−02), stroke (OR = 1.06, 95% CI: 1.01–1.12, p = 2.79E−02), and coronary heart disease (OR = 1.19, 95% CI: 1.01–1.39, p = 3.33E−02), contributing to the understanding of the overlapping genetic mechanisms and therapeutic approaches between RA and cardiovascular disease.

scholarly journals Estimating the causal effect of adiposity on carpal tunnel syndrome: a Mendelian randomization study

2019 ◽  
Author(s):  
Iyas Daghlas ◽  
Nathan Varady
Keyword(s):  
Type 2 Diabetes ◽  
Body Mass Index ◽  
Carpal Tunnel Syndrome ◽  
Carpal Tunnel ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Sensitivity Analyses ◽  
Abdominal Adiposity ◽  
Tunnel Syndrome

AbstractBackgroundWe aimed to examine evidence for a causal effect of overall and abdominal adiposity on carpal tunnel syndrome (CTS) using two-sample Mendelian randomization (MR).MethodsThe exposure included genetic instruments comprising independent variants associated with body mass index (BMI) (n=322,154), a proxy for overall adiposity, and waist-hip ratio adjusted for BMI (WHRadjBMI) (n=210,082), a proxy for abdominal adiposity. Associations of these variants with CTS were obtained from a genome-wide association study (GWAS) conducted in UK Biobank (12,312 CTS cases / 389,344 controls). Causal effects were estimated using inverse-variance weighted regression and conventional MR sensitivity analyses were conducted to assess for horizontal pleiotropy. In follow-up analyses we determined whether type 2 diabetes (T2D) or hyperlipidemia mediated the observed effects.ResultsA 1-standard deviation (SD, ∼4.7kg/m2) increase in genetically instrumented BMI increased the risk of CTS (OR 1.73, 95% CI 1.48-2.02, p=2.68e-12), with consistent effects across sensitivity analyses. This effect translates to an absolute increase of 17 CTS cases per 1000 person years amongst US working populations [95% CI 11.0-23.5]. Univariable MR was consistent with a causal effect of T2D (OR 1.08, 95% CI 1.03-1.11, p=5.20e-05), and the effect of BMI was partially attenuated (OR 1.53, 95% CI 1.38-1.68, p=2.85e-08) when controlling for T2D liability in multivariable MR. In contrast, no effect was observed of WHRadjBMI on CTS (OR 1.03, 95% CI 0.74-1.33, p=0.83).ConclusionThese data support a causal effect of overall adiposity on susceptibility to CTS that is only partially mediated through T2D, suggesting that efforts to reduce obesity may mitigate the population burden of CTS.Key messages- A one-standard deviation increase in body mass index, a proxy for overall adiposity, increased risk of carpal tunnel by 73%. In contrast, no effect of waist-to-hip ratio adjusted for BMI, a proxy for abdominal adiposity, was observed on risk of carpal tunnel syndrome.- The effects of BMI on carpal tunnel syndrome risk were partially attenuated when accounting for mediation through type 2 diabetes, suggesting that the majority of the causal effect operates independently of diabetes risk.- These data suggest that efforts to reduce rates of obesity could reduce the incidence of carpal tunnel syndrome.

scholarly journals Sex Differences in the Risk of Coronary Heart Disease Associated With Type 2 Diabetes: A Mendelian Randomization Analysis

Diabetes Care ◽  
2020 ◽  
pp. dc201137
Author(s):  
Tricia M. Peters ◽  
Michael V. Holmes ◽  
J. Brent Richards ◽  
Tom Palmer ◽  
Vincenzo Forgetta ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Coronary Heart Disease ◽  
Sex Differences ◽  
Heart Disease ◽  
Mendelian Randomization ◽  
Mendelian Randomization Analysis ◽  
Randomization Analysis

scholarly journals The role of glycaemic and lipid risk factors in mediating the effect of BMI on coronary heart disease: A two-step, two-sample Mendelian randomization study

2017 ◽  
Author(s):  
Lin Xu ◽  
Maria Carolina Borges ◽  
Gibran Hemani ◽  
Deborah A Lawlor
Keyword(s):  
Risk Factors ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Research Council ◽  
Mendelian Randomization ◽  
Fasting Glucose ◽  
Causal Effect ◽  
Hdl Cholesterol

AbstractBackgroundThe extent to which effects of BMI on coronary heart disease (CHD) are mediated by gylcaemic and lipid risk factors is unclear.MethodsWe used two-sample Mendelian randomization to determine the causal effect of: (i) BMI on CHD (60,801 cases; 123, 504 controls), type 2 diabetes (T2DM; 34,840 cases; 114,981 controls), fasting glucose (n=46,186), insulin (n=38,238), HbA1c (n=46,368), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C) and triglycerides (n=188,577); (ii) glycaemic and lipids traits on CHD; and (iii) extent to which these traits mediated any effect of BMI on CHD.FindingsOne standard deviation (SD) increase in BMI (~ 4.5kg/m2) increased CHD (odds ratio=1.45 (95% confidence interval (CI): 1.27, 1.66)) and T2DM (1.96 (1.35, 2.83)), and levels of fasting glucose (0.07mmol/l (95%CI 0.03, 0.11)), HbA1c (0.05% (95%CI 0.01, 0.08)), fasting insulin (0.18log pmol/l (95%CI 0.14, 0.22)) and triglycerides (0.20 SD (95%CI 0.14, 0.26)), and lowered levels of HDL-C (−0.23 SD (95%CI −0.32, −0.15)). BMI was not causally related to LDL-C. After accounting for potential pleiotropy, triglycerides, HbA1c and T2DM were causally related to CHD. The BMI-CHD effect reduced from 1.45 to 1.16 (95%CI 0.99, 1.36) and to 1.36 (95%CI 1.19, 1.57) with genetic adjustment for triglycerides or HbA1c respectively, and to 1.09 (95%CI 0.94, 1.27) with adjustment for both.InterpretationIncreased triglyceride levels and poor glycaemic control appear to mediate much of the effect of BMI on CHD.FundingEuropean Research Council (669545), European Union (733206), China Medical Board (CMB_2015/16), Conselho Nacional de Desenvolvimento Científico e Tecnológico and UK Medical Research Council (MC_UU_12013/5).

scholarly journals A robust and efficient method for Mendelian randomization with hundreds of genetic variants: unravelling mechanisms linking HDL-cholesterol and coronary heart disease

2019 ◽  
Author(s):  
Stephen Burgess ◽  
Christopher N Foley ◽  
Elias Allara ◽  
James R Staley ◽  
Joanna MM Howson
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Efficient Method ◽  
Genetic Variants ◽  
Mendelian Randomization ◽  
Mean Squared Error ◽  
Causal Effect ◽  
Hdl Cholesterol ◽  
Distribution Width ◽  
Chd Risk

Mendelian randomization (MR) investigations with large numbers of genetic variants are becoming increasingly common. However, the reliability of findings from a MR investigation is dependent on the validity of the genetic variants as instrumental variables. We developed a method to identify groups of genetic variants with similar causal effect estimates, which may represent distinct mechanisms by which the risk factor influences the outcome. Our contamination mixture method is a robust and efficient method for valid MR in the presence of invalid IVs. Compared to other robust methods, our method had the lowest mean squared error across a range of realistic scenarios. The method is fast and efficient, and can perform analysis with hundreds of variants in a fraction of a second. In a MR analysis for high-density lipoprotein (HDL) cholesterol and coronary heart disease (CHD) risk, the method identified 11 variants associated with increased HDL-cholesterol, decreased triglyceride levels, and decreased CHD risk that had the same directions of associations with platelet distribution width and other blood cell traits, suggesting a shared mechanism linking lipids and CHD risk relating to platelet aggregation.

scholarly journals Lower Extremity Peripheral Arterial Disease Is an Independent Predictor of Coronary Heart Disease and Stroke Risks in Patients with Type 2 Diabetes Mellitus in China

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Xiao-Hong Pang ◽  
Jue Han ◽  
Wan-Lan Ye ◽  
Xue Sun ◽  
Yue Ding ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Coronary Heart Disease ◽  
Heart Disease ◽  
Lower Extremity ◽  
Stroke Risk ◽  
Independent Predictor ◽  
Arterial Disease ◽  
Chd Risk ◽  
Peripheral Arterial

We aimed to determine the relationship between lower extremity peripheral arterial disease (PAD), 10-year coronary heart disease (CHD), and stroke risks in patients with type 2 diabetes (T2DM) using the UKPDS risk engine. We enrolled 1178 hospitalized T2DM patients. The patients were divided into a lower extremity PAD group (ankle-brachial index≤0.9 or >1.4; 88 patients, 7.5%) and a non-PAD group (ankle-brachial index>0.9 and ≤1.4; 1090 patients, 92.5%). Age; duration of diabetes; systolic blood pressure; the hypertension rate; the use of hypertension drugs, ACEI /ARB, and statins; CHD risk; fatal CHD risk; stroke risk; and fatal stroke risk were significantly higher in the PAD group than in the non-PAD group (P<0.05 for all). Logistic stepwise regression analysis indicated that ABI was an independent predictor of 10-year CHD and stroke risks in T2DM patients. Compared with those in the T2DM non-PAD group, the odds ratios (ORs) for CHD and stroke risk were 3.6 (95% confidence interval (CI), 2.2–6.0; P<0.001) and 6.9 (95% CI, 4.0–11.8; P<0.001) in those with lower extremity PAD, respectively. In conclusion, lower extremity PAD increased coronary heart disease and stroke risks in T2DM.

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