Physical Frailty, Genetic Predisposition, and Incident Heart Failure

There is growing interest in the intersection of frailty and heart failure (HF); however, large-sample longitudinal studies in the general population are lacking.

The goal of this study was to examine the longitudinal relationship between frailty and incident HF, and whether age and genetic predisposition could modify this association.

This prospective cohort study included 340,541 participants (45.7% male; mean age 55.9 ± 8.1 years) free of HF at baseline in the UK Biobank. Frailty was assessed by using the Fried frailty phenotype and included weight loss, exhaustion, low physical activity, slow gait speed, and low grip strength. The weighted polygenetic risk score was calculated. Cox models were used to estimate these associations and the interaction between the 2 factors.

During a median 14.1 years of follow-up, 7,590 patients with HF were documented. Compared with nonfrail participants, both prefrail and frail participants had a positive association with the risk of incident HF (prefrail HR: 1.40 [95% CI: 1.17-1.67]; frail HR: 2.07 [95% CI: 1.67-2.57]). Exhaustion (HR: 1.21; 95% CI: 1.03-1.43), slow gait speed (HR: 1.62; 95% CI: 1.39-1.90), and low grip strength (HR: 1.31; 95% CI: 1.14-1.51) were associated with a greater risk of incident HF. Furthermore, genetic susceptibility did not significantly modify the associations (P _interaction = 0.094), and the association was significantly strengthened in younger participants (P _interaction = 0.008).

Frailty status was associated with a higher risk of incident HF independent of genetic risk. A younger population may be more susceptible to HF when exposed to frailty. Whether the modification of frailty status represents another avenue for preventing HF warrants further investigation.