Association of Biological Age Acceleration with Cardiac Morphology, Function, and Incident Heart Failure: Insights from UK Biobank Participants

Eur Heart J Cardiovasc Imaging. 2024 May 15:jeae126. doi: 10.1093/ehjci/jeae126. Online ahead of print.

Abstract

Background: Advanced age is associated with an increased risk of adverse cardiovascular events. The relationship between biological age acceleration (BAA), cardiac size, cardiac function, and heart failure (HF) is not well-defined.

Methods: Utilizing the UK Biobank cohort, we assessed biological age using the Klemera-Doubal and PhenoAge method. BAA was quantified by residual analysis compared to chronological age. Cardiovascular magnetic resonance (CMR) imaging provided detailed insights into cardiac structure and function. We employed multivariate regression to examine links between BAA and CMR-derived cardiac phenotypes. Cox proportional hazard regression models analyses was applied to explore the causative relationship between BAA and HF. Additionally, Mendelian randomization was used to investigate the genetic underpinnings of these associations.

Results: A significant correlation was found between increased BAA and deleterious changes in cardiac structure, such as diminished left ventricular mass, lower overall ventricular volume, and reduced stroke volumes across ventricles and atria. Throughout a median follow-up of 13.8 years, participants with greater biological aging showed a heightened risk of HF (26% per standard deviation [SD] increase in KDM-BA acceleration, 95% confidence intervals [CI]: 23%-28%; 33% per SD increase in PhenoAge acceleration, 95% CI: 32%-35%). Mendelian randomization analysis suggests a likely causal link between BAA, vital cardiac metrics, and HF risk.

Conclusions: In this cohort, accelerated biological aging may serve as a risk indicator for altered cardiac dimensions, functionality, and the onset of heart failure among middle-aged and elderly adults. It holds promise as a focal point for evaluating risk and developing targeted interventions.

Keywords: Cardiovascular magnetic resonance; KDM-BA acceleration; PhenoAge acceleration; UK biobank.