Accelerated biological aging elevates the risk of cardiometabolic multimorbidity and mortality

Associations of biological aging with the development and mortality of cardiometabolic multimorbidity (CMM) remain unclear. Here we conducted a multistate analysis in 341,159 adults of the UK Biobank. CMM was defined as the coexistence of two or three cardiometabolic diseases (CMDs), including type 2 diabetes, ischemic heart disease and stroke. Biological aging was measured using the Klemera-Doubal Method Biological Age and PhenoAge algorithms. Over a median follow-up of 8.84 years, biologically older participants demonstrated robust higher risks from first CMD to CMM and then to death. In particular, adjusted hazard ratios for first CMD to CMM and for CMM to death were 1.15 (95% confidence interval (CI): 1.12, 1.19) and 1.26 (95% CI: 1.17, 1.35) per 1 s.d. increase in PhenoAge acceleration, respectively. Compared with frailty, Framingham Risk Score and Systematic Coronary Risk Evaluation 2 (SCORE2), biological aging measures yielded consistent substantial associations with CMM development. Accelerated biological aging may help identify individuals with CMM risks, potentially enabling early intervention and subclinical prevention.