Association between cardiovascular risk factors and dilated and hypertrophic cardiomyopathy: Mendelian randomization analysis

• Published in: Nutrition, metabolism, and cardiovascular diseases metabolism, and cardiovascular diseases, 2025-01, Vol.35 (1), p.103752, Article 103752
• Main Authors: Zou, Chenchao, Zou, Huaxi, Jiang, Ying, Lai, Songqing, Liu, Jichun
• Format: Article
• Language: English
• Subjects: Alcohol; Alcohol Drinking - adverse effects; Alcohol Drinking - epidemiology; Cardiomyopathy, Dilated - diagnosis; Cardiomyopathy, Dilated - epidemiology; Cardiomyopathy, Dilated - genetics; Cardiomyopathy, Hypertrophic - diagnosis; Cardiomyopathy, Hypertrophic - epidemiology; Cardiomyopathy, Hypertrophic - genetics; Dilated cardiomyopathy; Genetic Predisposition to Disease; Genome-Wide Association Study; Heart Disease Risk Factors; Humans; Hypertrophic cardiomyopathy; Mendelian Randomization Analysis; Obesity; Obesity - diagnosis; Obesity - epidemiology; Obesity - genetics; Phenotype; Polymorphism, Single Nucleotide; Risk Assessment; Risk Factors; Smoking; Smoking - adverse effects; Smoking - epidemiology
• ISSN: 0939-4753; 1590-3729; 1590-3729
• DOI: 10.1016/j.numecd.2024.09.022

Dilated cardiomyopathy is a major cause of heart failure, and hypertrophic cardiomyopathy is a common cause of sudden cardiac death in young adults. Epidemiological studies reporting the association between these cardiomyopathies and common cardiovascular risk factors, including smoking, alcohol, and obesity, are limited, and the published studies are mostly observational, making them vulnerable to bias. We performed a two-sample Mendelian randomization analysis to assess whether cardiovascular risk factors were causally associated with dilated and hypertrophic cardiomyopathies. Independent genetic variants associated with body mass index, smoking, and alcohol were selected as instrumental variables, with two sets of instrumental variables utilized for alcohol. Dilated cardiomyopathy data on 355,318 samples and hypertrophic cardiomyopathy data on 489,727 samples were obtained from a European population-based genome-wide association study (GWAS) meta-analysis. The large GWAS data sample size improved the statistical power. Our results showed significant associations between a genetic predisposition for smoking and the risk of dilated cardiomyopathy (odds ratio (OR) = 1.33; 95 % confidence level (CI): 1.07–1.67; p = 0.012) and between a genetic predisposition for obesity and the risk of dilated cardiomyopathy (OR = 1.62; 95 % CI, 1.30–2.02; p = 1.51 × 10−5). The results of the other associations were not significant. This study suggests that smoking and obesity are causally associated with an increased risk of dilated cardiomyopathy. •Epidemiologic studies on the effects of cardiovascular risk factors on dilated cardiomyopathy and hypertrophic cardiomyopathy are rare, the present study is a meaningful addition.•Regarding alcohol, we used two complementary sets of instrumental variables, alcohol intake frequency (AIF) and alcohol consumption (AC).•The GWAS data in this study were all large sample size data.