Effects of childhood obesity on heart failure and its associated risk factors in the European population: A Mendelian randomization study.

BACKGROUND AND AIMS: Observational studies have shown that obesity considerably affects the cardiovascular system. Thus we conducted this Mendelian randomization (MR) analysis to evaluate the causal effect of childhood obesity on heart failure (HF) and its risk factors.

METHODS AND

RESULTS

We obtained genetic instruments from genome-wide association studies (GWAS) that investigated childhood obesity, HF, type 2 diabetes mellitus (T2DM), atrial fibrillation (AF), coronary artery disease (CAD), myocardial infarction (MI), chronic kidney disease (CKD), valvular heart disease, myocarditis, hypertrophic cardiomyopathy, and hyperthyroidism. Inverse variance weighting (IVW), weighted median analysis, MR-Egger, and MR-pleiotropy residual sum and outlier (MR-PRESSO) were employed for MR analyses. In addition, the leave-one-out sensitivity test, MR-PRESSO global test, and Cochran's Q test were used for sensitivity analyses. Genetic evaluations showed that childhood obesity increases the risk of HF (odds ratio [OR] = 1.11, 95%CI: 1.05-1.17, p = 1.26 × 10-4), T2DM (OR = 1.17, 95%CI: 1.12-1.23, p = 8.80 × 10-12), AF (OR = 1.08, 95%CI: 1.05-1.12, p = 2.66 × 10-7), MI (OR = 1.08, 95%CI: 1.04-1.13, p = 3.35 × 10-4), and CAD (OR = 1.08, 95%CI: 1.03-1.13, p = 1.48 × 10-3). We found no association between childhood obesity and CKD, valvular heart disease, myocarditis, hypertrophic cardiomyopathy, or hyperthyroidism. Sensitivity analysis and Bonferroni's correction showed consistent results.

CONCLUSIONS

Our study provides new evidence for the relationship between childhood obesity and HF and its risk factors. The results indicate that individuals with a history of childhood obesity require more clinical attention to prevent the development of HF.