Physical frailty, genetic predisposition, and risk of incident degenerative aortic valve stenosis: A prospective cohort study

Cross-sectional evidence has implicated a high prevalence of frailty in patients with aortic valve stenosis (AS); however, the longitudinal association remains unknown. This study aimed to examine the longitudinal association between the physical frailty phenotype and the incidence of AS in middle-aged and older adults. Prospective cohort and longitudinal study SETTING: A population-based study of middle-aged and older adults. This study included participants from the UK biobank study. Physical frailty was assessed using the Fried criteria frailty phenotype in the UK biobank in more than half a million participants. The primary outcome was incident degenerative AS, and the secondary outcome was AS-related events, that is, AS-related intervention or death due to AS. Cox proportional hazards models and competing risk models were used to evaluate their associations. Among 480,967 participants (median age, 58.0 years; 54.6% female), 5,589 AS cases and 2,336 AS-related events were documented during a median follow-up of 14.3 years. Compared with robust participants, the adjusted hazard ratio (HR) in prefrail and frail participants was 1.30 (95% CI, 1.22-1.38) and 1.66 (95% CI, 1.50-1.84) for incident AS and 1.31 (95% CI, 1.19-1.43) and 1.54 (95% CI, 1.30-1.81) for AS-related events, respectively. The results were similar in a series of sensitivity analyses. Compared with robust participants with low genetic risk, frail participants with high genetic risk had the highest risk of AS (HR, 2.56; 95% CI, 2.15-3.06). Progression from robust to frail (HR, 2.41; 95% CI, 1.17-4.98) was associated with increased AS risk, while recovery from prefrail/frail to robust (HR, 0.35; 95% CI, 0.18-0.69) was associated with decreased AS risk. Physical prefrailty and frailty were associated with incident AS and subsequent AS-related events. These findings highlight the importance of integrating frailty assessment into the primary prevention of AS to better identify high-risk individuals.