Accelerated biological aging, cardiovascular risks, and cardiometabolic multimorbidity: a cohort study

Abstract

AbstractBackgroundCardiometabolic multimorbidity (CMM) is the coexistence of two or three cardiometabolic diseases (CMDs), including diabetes, ischemic heart disease (IHD), and stroke, which are recognized as cardiometabolic physiology changes with aging. However, whether accelerated biological aging is associated with the trajectories of CMM development remains poorly understood.ObjectivesTo evaluate the association between accelerated biological aging and the trajectories of CMM.MethodsBaseline accelerated biological aging status of 341,159 adults from UK Biobank was assessed by the Klemera-Doubal method biological age (KDM-BA), PhenoAge, and frailty status. A multi-state model was employed to evaluate their associations with CMM trajectories and corresponding prediction capacities.ResultsDuring a median follow-up of 8.84 years, 26,319 participants developed at least one CMD, 2,502 of which subsequently developed CMM. Robust associations were observed between three aging measures and the risk from the first CMD (FCMD) to CMM. Adjusted HRs from FCMD to CMM of PhenoAge acceleration and KDM-BA acceleration were 1.15 (95% CI: 1.12–1.19) and 1.14 (95% CI: 1.08–1.21), respectively, and the HRs of frail individuals were 1.33 (95% CI: 1.15–1.53) compared to the non-frail. Classifying the FCMD into three individual cardiovascular diseases, we observed three aging measures separately indicated risk projections to CMM from each disease. People with accelerated aging were with 10 ~ 30% higher probability of death from FCMD or CMM than from baseline. PhenoAge acceleration could predict the CMM risk the best individually (Harrell C-statistics = 0.6254). Two cardiovascular risk scores, Framingham risk score and SCORE2, yielded similar prediction power, but with much reduced risk estimates compared to aging measures.ConclusionsAccelerated biological aging provide a reservoir for a better prediction of cardiometabolic aging to optimize the subclinical prevention of CMM, and could be targeted for may provide a novel target for early intervention.