Adult Height, Cardiovascular Disease, and the Underlying Mechanism: A Comprehensive Epidemiological and Genetic Analysis.

Abstract

Background: Adult height measures the complete growth of an individual and influences the development of cardiovascular diseases (CVD). Despite recent within-sibling studies suggesting minimal impact from environmental confounders, biological mechanisms underlying the height-CVD relationship remain elusive.

Methods: Leveraging the large-scale UK biobank dataset and summary statistics from the latest genome-wide association studies (GWAS), we re-evaluated the effect of height on 8 major CVD subtypes. Phenotypic associations were determined by Cox proportional hazard analysis. Putative causal relationships were assessed through univariable Mendelian randomization (MR). Mediation analysis and two-step MR were further performed to investigate the mediation effect of 15 common cardiometabolic or pulmonary risk factors.

Results: Height was consistently associated with a decreased risk of coronary artery disease (CAD), confirmed by both epidemiological (HR = 0.90, 95%CI = 0.88-0.91) and genetic (OR = 0.89, 95%CI = 0.86-0.92) analysis. Forced vital capacity (FVC) was identified as the most significant mediator for height-CAD relationship by both epidemiological (proportion mediated (PM) = 65.6%, 95%CI = 53.1%-78.0%) and genetic (PM = 46.2%, 95%CI = 5.0%-87.5%) analysis. Notably, obesity, blood pressure, lipids, and C-reactive protein also exhibited significant mediatory effects. Despite a consistent risk effect of height on atrial fibrillation (AF) and venous thromboembolism (VTE), no promising mediator was identified.

Conclusion: Our study confirms the health impact of height on CAD, AF and VTE and emphasizes FVC as the primary pathway linking height to CAD. Importantly, it indicates that the CAD risk associated with non-modifiable height could be mitigated through enhanced lung function and cardiometabolic conditions.