Contribution of metabolic risk factors and lifestyle behaviors to cardiovascular disease: A mendelian randomization study.
Level 3 - non-randomized controlled study
Mendelian randomization study using summary-level genetic data, graded Level 3 by design analogy to observational cohort/instrumental variable analysis.
PubMed 35610082 · doi:10.1016/j.numecd.2022.04.019
What was done
The authors conducted a two-sample Mendelian randomization (MR) analysis evaluating the potential causal effects of 15 modifiable metabolic risk factors and lifestyle behaviors on coronary artery disease (CAD) and ischemic stroke. Genetic instrumental variables for blood pressure, glucose, lipids, overweight, smoking, alcohol intake, sedentariness, and education were derived from published genome-wide association studies (GWASs). Summary-level outcome data were extracted from large GWAS datasets: CAD (60,801 cases / 123,504 controls) and ischemic stroke (40,585 cases / 406,111 controls).
What was found
Genetically predicted levels of 11 modifiable factors showed significant causal associations with CVD outcomes: - Hypertension: CAD OR 5.19 (95% CI, 4.21-6.41); ischemic stroke OR 4.92 (95% CI, 4.12-5.86) - Systolic BP: CAD OR 1.03 (95% CI, 1.03-1.04); ischemic stroke OR 1.03 (95% CI, 1.03-1.03) - Diastolic BP: CAD OR 1.05 (95% CI, 1.05-1.06); ischemic stroke OR 1.05 (95% CI, 1.04-1.05) - Type 2 diabetes: CAD OR 1.11 (95% CI, 1.08-1.15); ischemic stroke OR 1.07 (95% CI, 1.04-1.10) - Smoking initiation: CAD OR 1.26 (95% CI, 1.18-1.35); ischemic stroke OR 1.24 (95% CI, 1.16-1.33) - Educational attainment: CAD OR 0.62 (95% CI, 0.58-0.66); ischemic stroke OR 0.68 (95% CI, 0.63-0.72) - Low-density lipoprotein cholesterol: CAD OR 1.55 (95% CI, 1.41-1.71) - High-density lipoprotein cholesterol: CAD OR 0.82 (95% CI, 0.74-0.91) - Triglycerides: CAD OR 1.29 (95% CI, 1.14-1.45) - Body mass index: CAD OR 1.25 (95% CI, 1.19-1.32) - Alcohol dependence: OR 1.04 (95% CI, 1.03-1.06)
Why it matters
This study provides genetic evidence prioritizing 11 modifiable metabolic and lifestyle factors as potential targets for coronary artery disease and ischemic stroke prevention.
Limits
The abstract does not provide numerical results for 4 of the 15 tested modifiable factors (e.g., sedentariness). Outcome-specific estimates for some factors (lipids, BMI, alcohol dependence) are presented selectively for CAD or combined CVD. Population demographics, ancestral diversity, and potential bias from horizontal pleiotropy are not detailed in the abstract.
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