Joint Associations of Frailty and Cardiometabolic Diseases With Risk of All-Cause and Cardiac Mortality.

Background: Cardiometabolic diseases (CMDs) are common for middle-aged and older adults. Whether frailty exacerbates CMD-related risk of mortality outcomes is unclear.

Objectives: The authors sought to investigate the joint associations of frailty and CMDs with mortality risk.

Methods: This prospective cohort study included 467,406 participants from UK biobank. Frailty was assessed using frailty phenotype and frailty index (FI). CMD status was defined as no CMD, single CMD, and cardiometabolic multimorbidity (CMM, coexistence of ≥2 CMDs). Multiplicative and additive interactions between frailty and CMDs two exposures on all-cause and cardiac mortality were examined, and then the joint association of coexisting frailty and CMDs with outcomes were estimated.

Results: During median follow-up of 13.08 years, 33,435 participants (7.2%) died, with 6,709 (1.4%) experiencing cardiac mortality. For frailty phenotype measurement, significant multiplicative and additive interactions existed with CMD status. Coexisting frailty phenotype and CMM were associated with a 4.91 (95% CI: 4.49-5.38) times and 8.33 (95% CI: 7.13-9.72) times higher risk of all-cause and cardiac mortality, with 23% and 36% attributable to the additive interaction, respectively. For FI measurements, a significant multiplicative interaction was observed with CMDs, and similar frailty-CMD joint associations with mortality outcomes were also observed.

Conclusions: Coexisting frailty and CMDs were associated with an accumulatively increased risk of mortality. Comprehensive screening and management of frailty and CMDs is advisable in aged populations.