Association of biological age acceleration with cardiovascular disease and premature mortality: a population-based prospective cohort study

Introduction Accelerated biological ageing is associated with age-related diseases, but sex differences in its association with cardiovascular disease (CVD) and premature mortality remain largely unknown. We aimed to assess the associations between biological age (BA) acceleration and CVD, premature mortality, and examine potential sex differences. Methods This population-based prospective cohort study included participants aged 39 to 71 years from UK Biobank study, recruited between 2006 and 2010, and followed up until Dec 20, 2022. BA, derived from clinical biomarkers, was calculated using the Klemera-Doubal method (KDM-BA) and PhenoAge algorithms. BA acceleration was defined as the residual from regressing BA based on chronological age. Incident CVD and premature mortality (defined as death before age 70) were identified using ICD-9 and ICD-10 codes. Multivariable-adjusted Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) across BA acceleration quartiles. Results Among 122,133 participants who were free of CVD at baseline (mean [SD] age, 56.0 [8.1] years; 65,442 [53.6%] women), 24,281 incident CVD cases and 3,614 premature deaths were reported. Restricted cubic splines showed progressively increasing risks of incident CVD and premature mortality associated with higher BA acceleration. Compared with the lowest quartile of KDM-BA acceleration, the largest adjusted HRs for incident CVD and premature mortality were 1.32 (95% CI 1.27–1.37) and 1.10 (95% CI 1.05–1.21) for quartile 4, respectively. For PhenoAge acceleration, the corresponding HRs were 1.23 (95% CI 1.19–1.28) and 1.21 (95% CI 1.10–1.33), respectively. These associations were more pronounced among male participants ( P -interaction