Abstract P324: Body Mass Index, Walking Pace, and Risk of Coronary Heart Disease: a Mendelian Randomization and Mediation Analysis

Background: We applied a network Mendelian randomization (MR) framework to determine the causal association between body mass index (BMI) and coronary heart disease (CHD) and explored whether glycated hemoglobin (HbA1c) and lipid parameters (total cholesterol, TC; low-density lipoprotein cholesterol, LDL; high-density lipoprotein cholesterol, HDL; triglycerides, TG) serve as causal mediators from BMI to CHD by integrating summary-level genome-wide association study data. Methods: Network MR analysis, an approach using genetic variants as the instrumental variables for both the exposure and mediator to infer causality was performed. Summary statistics from the GIANT consortium were used ( n = 152,893) for BMI, CARDIoGRAMplusC4D consortium data were used ( n = 184,305) for CHD, Global Lipids Genetics Consortium data were used ( n = 108,363) for TC, LDL, HDL and TG, and MAGIC consortia data were used ( n = 108,363) for HbA1c. Results: The inverse-variance-weighted-method estimate indicated that the odds ratio (95% confidence interval) for CHD was 1.562 (1.391–1.753) per 1 standard deviation (kg/m2) increase in BMI. Results were consistent in MR Egger method and weighted-median methods. MR estimate indicated that BMI was positively associated with HbA1c and TG, and negatively associated with HDL, but was not associated with TC or LDL. Moreover, HbA1c, TC, LDL, and TG were positively associated with CHD, yet there was no causal association between HDL and CHD. HbA1c was positively associated with TC, LDL, and HDL, but was not associated with TG. Conclusions: Higher BMI conferred an increased risk of CHD, which was partially mediated by HbA1c and lipid parameters. HbA1c and TG might be the main mediators in the link from BMI to CHD.

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What explains the effect of education on cardiovascular disease? Applying Mendelian randomization to identify the consequences of education inequality

10.1101/488254 ◽

2018 ◽

Cited By ~ 2

Author(s):

Alice R Carter ◽

Dipender Gill ◽

Neil M Davies ◽

Amy E Taylor ◽

Taavi Tillmann ◽

...

Keyword(s):

Risk Factors ◽

Blood Pressure ◽

Cardiovascular Disease ◽

Body Mass Index ◽

Coronary Heart Disease ◽

Heart Disease ◽

Systolic Blood Pressure ◽

Body Mass ◽

Mendelian Randomization

Key PointsQuestionWhat is the role of body mass index, systolic blood pressure and smoking in mediating the effect of education on cardiovascular disease risk?FindingWe find consistent evidence that body mass index, systolic blood pressure and smoking mediate the effect of education, explaining up to 18%, 27% and 33% respectively. Including all three risk factors in a model together explains around 40% of the effect of education.MeaningIntervening on body mass index, systolic blood pressure and smoking would lead to reductions in cases of CVD attributable to lower levels of education. Over half of the effect of education on risk of cardiovascular disease is not mediated through these risk factors.ImportanceLower levels of education are causally related to higher cardiovascular risk, but the extent to which this is driven by modifiable risk factors also associated with education is unknown.ObjectiveTo investigate the role of body mass index, systolic blood pressure and smoking in explaining the effect of education on risk of cardiovascular disease outcomes.DesignMultivariable regression analysis of observational data and Mendelian randomization (MR) analysis of genetic data.SettingUK Biobank and international genome-wide association study consortia.ParticipantsPredominantly individuals of European ancestry.Main outcomes and measuresThe effects of education (per 1-standard deviation increase, equivalent to 3.6 years) on coronary heart disease, cardiovascular disease (all subtypes), myocardial infarction and stroke risk (all measured in odds ratio, OR), and the degree to which this is mediated through body mass index, systolic blood pressure and smoking.ResultsEach additional standard deviation of education associated with 13% lower risk of coronary heart disease (OR 0.87, 95% confidence interval [CI] 0.84 to 0.89) in observational analysis and 37% lower risk (OR 0.63, 95% CI 0.60 to 0.67) in Mendelian randomization analysis. As a proportion of the total risk reduction, body mass index mediated 15% (95% CI 13% to 17%) and 18% (95% CI 14% to 23%) in the observational and Mendelian randomization estimates, respectively. Corresponding estimates for systolic blood pressure were 11% (95% CI 9% to 13%) and 21% (95% CI 15% to 27%), and for smoking, 19% (15% to 22%) and 33% (95% CI 17% to 49%). All three risk factors combined mediated 42% (95% CI 36% to 48%) and 36% (95 % CI 16% to 63%) of the effect of education on coronary heart disease in observational and Mendelian randomization respectively. Similar results were obtained when investigating risk of stroke, myocardial infarction and all-cause cardiovascular disease.Conclusions and relevanceBMI, SBP and smoking mediate a substantial proportion of the protective effect of education on risk of cardiovascular outcomes and intervening on these would lead to reductions in cases of CVD attributable to lower levels of education. However, more than half of the protective effect of education remains unexplained and requires further investigation.

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Exploring the Causal Pathway From Body Mass Index to Coronary Heart Disease: A Network Mendelian Randomization Study

SSRN Electronic Journal ◽

10.2139/ssrn.3343625 ◽

2019 ◽

Author(s):

Xun Hu ◽

Xiao-dong Zhuang ◽

Wei-yi Mei ◽

Gang Liu ◽

Zhi-min Du ◽

...

Keyword(s):

Body Mass Index ◽

Coronary Heart Disease ◽

Heart Disease ◽

Body Mass ◽

Mendelian Randomization ◽

Causal Pathway

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Body Mass Index, Lipid Metabolism and Estrogens: Their Impact on Coronary Heart Disease

Current Medicinal Chemistry ◽

10.2174/0929867321666140901114515 ◽

2014 ◽

Vol 21 (30) ◽

pp. 3455-3465 ◽

Cited By ~ 13

Author(s):

G.D. Kolovou ◽

V. Kolovou ◽

P.M. Kostakou ◽

S. Mavrogeni

Keyword(s):

Body Mass Index ◽

Coronary Heart Disease ◽

Heart Disease ◽

Lipid Metabolism ◽

Body Mass

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Risk of coronary heart disease among cancer survivors with different prediagnosis body mass index

Scientific Reports ◽

10.1038/s41598-021-82026-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ahryoung Ko ◽

Kyuwoong Kim ◽

Joung Sik Son ◽

Yu Jin Cho ◽

Sang Min Park ◽

...

Keyword(s):

Body Mass Index ◽

Coronary Heart Disease ◽

Heart Disease ◽

Cancer Survivors ◽

Body Mass ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Cancer Site ◽

Chd Risk

AbstractAssociation between body mass index (BMI) and coronary heart disease (CHD) in cancer survivors is not clearly established. This study analyzed the prediagnosis BMI-CHD association by examining 13,500 cancer survivors identified from the National Health Insurance Service-Health Screening Cohort from January 1, 2004 to December 31, 2009 including the patients who were free of cardiovascular disease at enrollment. The Cox proportional hazards model (adjusted for socioeconomic, health behavior, health status, and medical characteristics) was used for calculating hazard ratios (HR) and 95% confidence intervals (95% CI) for CHD in each prediagnosis BMI category among cancer survivors. Compared to cancer survivors with a prediagnosis BMI between 18.5 and 22.9 kg/m2, those with a prediagnosis BMI of 23.0–24.9 kg/m2 and ≥ 25.0 kg/m2 had significantly higher CHD risk (HR = 1.51; 95% CI: 1.13–2.01 and HR = 1.38; 95% CI: 1.04–1.84, respectively). Cancer survivors with a low prediagnosis BMI (< 18.5 kg/m2) also had significantly higher CHD risk (HR = 1.97; 95% CI: 1.20–3.24) compared to those with a BMI of 18.5–22.9 kg/m2. Similar associations were found after stratifying analyses based on first cancer site and sociodemographic and medical characteristic subgroups. Our study suggests that prediagnosis underweight among patients with cancer is a predictor of CHD risk.

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