Contribution of metabolic risk factors and lifestyle behaviors to cardiovascular disease: A mendelian randomization study

• Published in: Nutrition, metabolism, and cardiovascular diseases Vol. 32; no. 8; pp. 1972 - 1981
• Main Authors: Jia, Yiming, Wang, Rong, Guo, Daoxia, Sun, Lulu, Shi, Mengyao, Zhang, Kaixin, Yang, Pinni, Zang, Yuhan, Wang, Yu, Liu, Fanghua, Zhang, Yonghong, Zhu, Zhengbao
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.08.2022
• Subjects: alcohol abuse; alcohol drinking; blood pressure; body mass index; Cardiovascular disease; Coronary artery disease; education; etiology; glucose; high density lipoprotein cholesterol; hypertension; Ischemic stroke; lifestyle; low density lipoprotein cholesterol; Mendelian randomization; metabolism; noninsulin-dependent diabetes mellitus; nutrition; overweight; Risk factors; MR-PRESSO; RCT; GWAS; OR; LDL-C; MR; CAD; CARDIOGRAMPLUSC4D; Cardiovascular disease; Ischemic stroke; Mendelian randomization; IVW; Coronary artery disease; Risk factors; BP; CVD; HDL-C; MEGASTROKE; RSS; STROBE-MR; SNP; LD; BMI
• ISSN: 0939-4753; 1590-3729; 1590-3729
• DOI: 10.1016/j.numecd.2022.04.019

Etiologic associations between some modifiable factors (metabolic risk factors and lifestyle behaviors) and cardiovascular disease (CVD) remain unclear. To identify targets for CVD prevention, we evaluated the causal associations of these factors with coronary artery disease (CAD) and ischemic stroke using a two-sample Mendelian randomization (MR) method. Previously published genome-wide association studies (GWASs) for blood pressure (BP), glucose, lipids, overweight, smoking, alcohol intake, sedentariness, and education were used to identify instruments for 15 modifiable factors. We extracted effects of the genetic variants used as instruments for the exposures on coronary artery disease (CAD) and ischemic stroke from large GWASs (N = 60 801 cases/123 504 controls for CAD and N = 40 585 cases/406 111 controls for ischemic stroke). Genetically predicted hypertension (CAD: OR, 5.19 [95% CI, 4.21–6.41]; ischemic stroke: OR, 4.92 [4.12–5.86]), systolic BP (CAD: OR, 1.03 [1.03–1.04]; ischemic stroke: OR, 1.03 [1.03–1.03]), diastolic BP (CAD: OR, 1.05 [1.05–1.06]; ischemic stroke: OR, 1.05 [1.04–1.05]), type 2 diabetes (CAD: OR, 1.11 [1.08–1.15]; ischemic stroke: OR, 1.07 [1.04-1.10]), smoking initiation (CAD: OR, 1.26 [1.18–1.35]; ischemic stroke: OR, 1.24 [1.16–1.33]), educational attainment (CAD: OR, 0.62 [0.58–0.66]; ischemic stroke: OR, 0.68 [0.63–0.72]), low-density lipoprotein cholesterol (CAD: OR, 1.55 [1.41–1.71]), high-density lipoprotein cholesterol (CAD: OR, 0.82 [0.74–0.91]), triglycerides (CAD: OR, 1.29 [1.14–1.45]), body mass index (CAD: OR, 1.25 [1.19–1.32]), and alcohol dependence (OR, 1.04 [1.03–1.06]) were causally related to CVD. This systematic MR study identified 11 modifiable factors as causal risk factors for CVD, indicating that these factors are important targets for preventing CVD. [Display omitted] •This study provided novel insight into the causal risk factors for cardiovascular diseases from a genetic standpoint.•This study further developed actionable prevention strategies against cardiovascular diseases.•Blood pressure, glucose, lipids, body mass index, smoking, alcohol intake, and education were promising preventive targets.