Cross-Ancestry Impact of Modifiable Cardiometabolic Risk Factors on Cardiomyopathy

Mendelian randomization analyses show that genetic evidence clarifies modifiable drivers of hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) across ancestries—identifying systolic and diastolic blood pressure, central adiposity, and alcohol consumption as principal, actionable exposures deserving clinical evaluation.

Analyses were performed separately in European and East Asian samples. The data indicate that systolic blood pressure (SBP) and diastolic blood pressure (DBP) are causal for HCM across ancestries. These associations were robust across sensitivity and multivariable MR analyses, supporting SBP control as a prevention priority when evaluating strategies to reduce HCM incidence.

Central adiposity demonstrated a causal relationship with DCM independent of BMI in both European and East Asian samples (DCM ORs ≈ 1.7 in Europeans and >3.0 in East Asians). This pattern suggests central fat distribution may more directly drive cardiomyopathic remodeling than BMI alone, making waist circumference a plausible target for risk stratification and prevention trials.

Genetic proxies for alcohol consumption were associated with higher DCM risk in both ancestries (approximate ORs: 1.5 in Europeans; 1.3 in East Asians), with ancestry differences in magnitude. Those differences could reflect dose–response biology, population drinking patterns, or genetic architecture that modifies alcohol‑related cardiotoxicity. Collectively, the evidence supports alcohol exposure as a likely modifiable contributor to DCM risk.