Changes in Frailty and Cardiometabolic Disease: Evidence From a Longitudinal Cohort Study and Genetic Analysis

Wenjie Wang; Kexin Wang; Guangyuan Chen; Jialong Niu; Yixuan Liu; Zhongke Wang; Hailong Ge

doi:10.1016/j.jacadv.2025.101782

Changes in Frailty and Cardiometabolic Disease: Evidence From a Longitudinal Cohort Study and Genetic Analysis

JACC Adv. 2025 Jun;4(6 Pt 2):101782. doi: 10.1016/j.jacadv.2025.101782.

Authors

Wenjie Wang¹, Kexin Wang¹, Guangyuan Chen², Jialong Niu¹, Yixuan Liu¹, Zhongke Wang¹, Hailong Ge³

Affiliations

¹ Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
² The First Hospital of Harbin, Harbin, Heilongjiang, China.
³ Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China. Electronic address: azccmu@163.com.

PMID: 40579064
DOI: 10.1016/j.jacadv.2025.101782

Abstract

Background: Cardiometabolic diseases (CMD) include coronary heart disease, stroke, and diabetes. Patients who have ≥2 CMD are defined as cardiometabolic multimorbidity (CMM). CMD and CMM have been associated with frailty, but studies are limited.

Objectives: The aim of this study was to examine the association between frailty index (FI), changes in frailty, and risks of CMD and CMM.

Methods: Data were obtained from the China Health and Retirement Longitudinal Study. Frailty status was classified into 3 categories: robust (FI ≤0.1), pre-frail (FI 0.1-0.25), and frail (FI ≥0.25). Total FI and change in FI (ΔFI) were divided into 3 tertiles. Mendelian randomization was used to clarify the relationship between FI and CMD from a genetic perspective.

Results: A total of 10,022 patients were included (female: 54.0%, median age: 57 years). Robust subjects who progressed to pre-frail/frail status had significantly increased risks of CMD (HR: 1.67, 95% CI: 1.46-1.92) and CMM (HR: 1.80, 95% CI: 1.30-2.50). Participants in the tertile 2 (HR: 1.48, 95% CI: 1.31-1.66) and tertile 3 of the total FI group (HR: 2.11, 95% CI: 1.87-2.37) had increased risks of developing CMD, compared with tertile 1. Participants in the upper tertile of the ΔFI group had higher risks of CMD (HR: 1.61, 95% CI: 1.44-1.80) and CMM (HR: 2.07, 95% CI: 1.61-2.66) than those in the first tertile.

Conclusions: Progression of frailty status elevates CMD and CMM risks. Higher total FI and ΔFI were also related to increased risks of CMD and CMM.

Keywords: CHARLS; Mendelian randomization; cardiometabolic diseases; cardiometabolic multimorbidity; epidemiology; frailty.