Phenotypic Age Acceleration and Risk of All-Cause and Cardiovascular Mortality in US Adults With Asthma: A Retrospective Cohort Study.

Background: Phenotypic age acceleration (PhenoAgeAccel) reflects biological aging, with higher values indicating faster aging. While linked to adverse outcomes in the general population, its relation to mortality in asthma remains unclear. Methods: We analyzed 3817 adults with physician-diagnosed asthma from NHANES (1999-2010, 2015-2018) with mortality follow-up through 2019. PhenoAgeAccel was calculated from clinical biomarkers, and associations with all-cause and cardiovascular mortality were assessed using weighted Cox models, restricted cubic splines, and subgroup/sensitivity analyses. Results: During a median follow-up of 13.2 years, higher PhenoAgeAccel was independently associated with greater risks of all-cause mortality (HR = 1.03, 95% CI: 1.03-1.04) and cardiovascular mortality (HR = 1.02, 95% CI: 1.01-1.04). Compared with the lowest quartile, participants in the highest had a 3.42-fold higher all-cause and 2.72-fold higher cardiovascular mortality risk. Associations were nonlinear for all-cause but roughly linear for cardiovascular mortality, and consistent across subgroups and sensitivity tests. Conclusions: Higher PhenoAgeAccel was independently associated with increased risks of all-cause and cardiovascular mortality among adults with asthma, indicating that biological aging markers may serve as useful tools for risk assessment and individualized care.