Causal Associations between Height and Heart Failure: A Mendelian Randomization Study

Background: Recent studies have suggested an association between height and heart failure (HF), yet findings have been inconsistent. To clarify this relationship, we utilized Mendelian randomization (MR) to investigate the potential causal link between height and HF. Methods: Independent single nucleotide polymorphisms (SNPs) associated with height were identified from genome-wide association studies data and used as instrumental variables. A two-sample MR approach was employed to explore the causal relationship between height and HF. For MR estimation, methods including inverse variance weighted (IVW), weighted median, MR-Egger, simple mode, and weighted mode were utilized. The stability and reliability of the results were assessed using Cochran’s Q statistic, MR-Egger intercept test, and the leave-one-out method. Additionally, multivariate Mendelian randomization (MVMR) analysis was conducted to determine if height had an independent effect on HF, adjusting for potential confounders such as body mass index, blood sugar, blood pressure, blood lipids, smoking and drinking habits, coffee intake, and physical activity. Results: The two-sample MR analysis demonstrated a significant causal association between genetically predicted height and the risk of HF. Using the IVW method, a one-standard deviation increase in genetically predicted height was associated with a 6% higher risk of HF (95% confidence interval [CI] = 1.01–1.13, P = 0.03). This suggests that height is a significant risk factor. Evidence from SNP heterogeneity was noted ( P < 0.001), with no indication of horizontal pleiotropy ( P = 0.32). Re-evaluation using a random effects model confirmed the positive causal relationship between height and HF ( P = 0.03), unaffected by heterogeneity. Further, after adjusting for confounding factors in the MVMR analysis, height continued to show an adverse effect on HF (odds ratio = 1.11, 95% CI = 1.03–1.16, P < 0.01). Conclusions: This study establishes a causal relationship between height and HF, indicating that for every one-unit increase in height, the risk of HF increases by 11.1%.