Accelerated biological aging leads to the trajectory of cardiometabolic multimorbidity to dementia and mortality

Context Cardiometabolic multimorbidity (CMM) and aging are increasing public health concerns.

Objective This study investigated the relationship between biological aging and the trajectory of CMM with dementia and mortality and the preventive value of Life’s Essential 8 (LE8) for biological aging.

Study design and setting This prospective analysis was conducted using a UK Biobank study. CMM is the coexistence of at least two cardiometabolic diseases (CMD), including stroke, ischemic heart disease, and type 2 diabetes. Biological age was calculated using the KDM-BA and PhenoAge algorithms using a clinical index.

Participants The study included 415,147 individuals with an average age of 56.5 years. Main

Outcome Measures The primary outcomes of this study were CMDs, CMM, all-cause dementia (Alzheimer’s disease, vascular dementia, and other causes), and all-cause mortality. The Cox proportional hazards model was used to examine the risk of adverse events associated with accelerated aging (biological age > chronological age).

Results During the average 11-year follow-up period, CMD-free individuals with accelerated aging had a significantly greater risk of developing CMD (KDM-BA, HR 1.456; PhenoAge, HR 1.404), CMM (KDM-BA, HR 1.952; PhenoAge, HR 1.738), dementia (KDM-BA, HR 1.243; PhenoAge, HR 1.212), and mortality (KDM-BA, HR 1.821; PhenoAge, HR 2.047) after adjustment for triditional risk factors (P<0.05 for all). Accelerated aging had adjusted HRs of 1.489 (KDM-BA) and 1.488 (PhenoAge) for CMM, 1.493 (KDM-BA) and 1.195 (PhenoAge) for dementia, and 1.951 (KDM-BA) and 1.985 (PhenoAge) for mortality in participants with CMD at baseline (P<0.05 for all). CMM significantly mediated accelerated aging’s indirect effects on dementia by 13.7% (KDM-BA, HR) and 21.6% (PhenoAge); those on mortality were 4.7% (KDM-BA) and 5.2% (PhenoAge). The population attributable-risk of LE8 score (≥80 vs. <80) were 0.79 and 0.43 for KDM-BA and PhenoAge accelerated aging, respectively.

Conclusions Biological aging involves the entire trajectory of CMM from a CMD-free state to CMD, to CMM, and ultimately to dementia and death. LE8 may be a potential target to counter age acceleration.