| Title: | Adult Height, Cardiovascular Disease, and the Underlying Mechanism: A Comprehensive Epidemiological and Genetic Analysis |
| Journal: | Canadian Journal of Cardiology |
| Published: | 31 Mar 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40174860/ |
| DOI: | https://doi.org/10.1016/j.cjca.2025.03.027 |
Publication 15968
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
BACKGROUND: Adult height measures the complete growth of an individual and influences the development of cardiovascular disease (CVD). Despite recent within-sibling studies that have suggested minimal effects from environmental confounders, biological mechanisms underlying the height-CVD relationship remain elusive.</p>
METHODS: Leveraging the large-scale UK Biobank data set and summary statistics from the latest genome-wide association studies, we reevaluated the effect of height on 8 major CVD subtypes. Phenotypic associations were determined using Cox proportional hazard analysis. Putative causal relationships were assessed using univariable Mendelian randomization. Mediation analysis and 2-step Mendelian randomization were further performed to investigate the mediation effect of 15 common cardiometabolic or pulmonary risk factors.</p>
RESULTS: Height was consistently associated with a decreased risk of coronary artery disease (CAD), confirmed in epidemiological (hazard ratio, 0.90; 95% confidence interval [CI], 0.88-0.91) and genetic (odds ratio, 0.89, 95% CI, 0.86-0.92) analysis. Forced vital capacity was identified as the most significant mediator for the height-CAD relationship in epidemiological (proportion-mediated, 65.6%; 95% CI, 53.1%-78.0%) and genetic (proportion-mediated, 46.2%; 95% CI, 5.0%-87.5%) analysis. Notably, obesity, and blood pressure, lipid, and C-reactive protein levels also exhibited significant mediatory effects. Despite a consistent risk effect of height on atrial fibrillation and venous thromboembolism, no promising mediator was identified.</p>
CONCLUSIONS: Our study confirms the health effects of height on CAD, atrial fibrillation, and venous thromboembolism and emphasizes forced vital capacity as the primary pathway that links height to CAD. Importantly, it indicates that the CAD risk associated with nonmodifiable height could be mitigated through enhanced lung function and cardiometabolic conditions.</p>
25 Authors
- Jinyu Xiao
- Jiayuan Li
- Xueyao Wu
- Yu Hao
- Xunying Zhao
- Wenqiang Zhang
- Bin Xu
- Tianpei Ma
- Li Zhang
- Rong Xiang
- Huijie Cui
- Chao Yang
- Peijing Yan
- Mingshuang Tang
- Yutong Wang
- Yang Qu
- Lin Chen
- Yunjie Liu
- Yanqiu Zou
- Ling Zhang
- Zhenmi Liu
- Yuqin Yao
- Chunxia Yang
- Ben Zhang
- Xia Jiang
Enabling scientific discoveries that improve human health