Key result
Genetically predicted higher systolic blood pressure was causally associated with an increased risk of hypertrophic cardiomyopathy in both European (OR 1.03) and East Asian (OR 1.06) populations.
Why the study?
Do genetically predicted modifiable cardiovascular risk factors increase the risk of hypertrophic and dilated cardiomyopathies in European and East Asian populations?
Observational (n=1,812,017)
Do genetically predicted modifiable cardiovascular risk factors increase the risk of hypertrophic and dilated cardiomyopathies in European and East Asian populations?
Genetically predicted higher systolic blood pressure is a causal risk factor for hypertrophic cardiomyopathy, while higher diastolic blood pressure, waist circumference, and alcohol consumption are causal risk factors for dilated cardiomyopathy across European and East Asian populations.
BACKGROUND: Potentially modifiable cardiovascular risk factors, including hypertension, diabetes, obesity, alcohol consumption, and smoking initiation, are associated with hypertrophic (HCM) and dilated (DCM) cardiomyopathies, representing promising targets for interventions. However, the causality and cross-ancestry generalizability of these associations remain uncertain. METHODS: Collecting summary-level data from genome-wide association studies for systolic (SBP) and diastolic (DBP) blood pressure, hypertension, type 2 diabetes, fasting glucose, glycated hemoglobin, body mass index (BMI), waist circumference (WC), alcohol consumption, smoking initiation, HCM, and DCM (sample size ranging from 38,288 to 1,812,017), we performed comprehensive two-sample univariable Mendelian randomization (MR) to evaluate the causal effect of each trait on HCM and DCM in both European and East Asian populations. We performed multivariable MR to investigate the independent effects of interrelated traits (SBP vs. DBP; BMI vs. WC). RESULTS: MR analyses identified reliable evidence of a causal effect of SBP on HCM (Europeans: odds ratio (OR) = 1.03, 95% confidence interval (CI) = 1.02-1.04; East Asians: OR = 1.06, 95% CI = 1.03-1.08). For DCM, reliable evidence of causal effects was identified for DBP (Europeans: OR = 1.04, 95% CI = 1.03-1.04; East Asians: OR = 1.07, 95% CI = 1.04-1.11), WC (Europeans: OR = 1.73, 95% CI = 1.58-1.89; East Asians: OR = 3.32, 95% CI = 1.22-9.03), and alcohol consumption (Europeans: OR = 1.50, 95% CI = 1.20-1.86; East Asians: OR = 1.32, 95% CI = 1.11-1.56). In Europeans, genetically predicted higher WC (OR = 1.75, 95% CI = 1.53-2.01) and smoking initiation (OR = 1.34, 95% CI = 1.16-1.56) specifically increased the risk of HCM and DCM, respectively, while genetically predicted higher alcohol consumption (OR = 1.68, 95% CI = 1.36-2.07) specifically increased the risk of HCM in East Asians. CONCLUSIONS: This study provided reliable cross-ancestry genetic evidence supporting higher SBP as a causal risk factor for HCM and higher DBP, WC, and alcohol consumption as causal risk factors for DCM. These findings underscore the potential of precision prevention strategies targeting modifiable cardiovascular risk factors to reduce cardiomyopathy burden across populations.
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Zhang et al. (2025) conducted an observational in Hypertrophic and dilated cardiomyopathies (n=1,812,017). Systolic blood pressure vs. Unexposed/reference group was evaluated on Hypertrophic cardiomyopathy (HCM) in Europeans (OR 1.03, 95% CI 1.02-1.04, p=7.14 x 10^-17). Genetically predicted higher systolic blood pressure was causally associated with an increased risk of hypertrophic cardiomyopathy in both European (OR 1.03) and East Asian (OR 1.06) populations.
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