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

Area of Science:

• Gerontology and Geriatric Medicine
• Cardiovascular Disease Epidemiology
• Public Health Research

Background:

• Cardiometabolic diseases (CMD), including coronary heart disease, stroke, and diabetes, pose significant health challenges.
• Cardiometabolic multimorbidity (CMM) is defined as having two or more CMDs.
• Frailty is increasingly recognized as a risk factor for CMD and CMM, though research remains limited.

Purpose of the Study:

• To investigate the association between frailty index (FI), frailty status changes, and the risks of developing CMD and CMM.
• To analyze how different levels of frailty and changes in frailty impact cardiometabolic health outcomes.

Main Methods:

• Utilized data from the China Health and Retirement Longitudinal Study (CHARLS).
• Classified participants into robust (FI ≤0.1), pre-frail (FI 0.1-0.25), and frail (FI ≥0.25) categories.
• Employed tertile analysis for total FI and change in FI (ΔFI), and utilized Mendelian randomization for genetic insights into FI and CMD relationships.

Main Results:

• Progression from robust to pre-frail/frail status significantly elevated risks for CMD (HR: 1.67) and CMM (HR: 1.80).
• Higher tertiles of total FI (tertile 2 HR: 1.48, tertile 3 HR: 2.11) and ΔFI (HR: 1.61 for CMD, HR: 2.07 for CMM) were associated with increased CMD and CMM risks compared to the lowest tertile.
• The study included 10,022 participants (54.0% female, median age 57).

Conclusions:

• Worsening frailty status is a significant predictor of increased risk for cardiometabolic diseases and multimorbidity.
• Elevated total frailty index and greater changes in frailty are independently associated with higher risks of CMD and CMM.
• These findings underscore the importance of monitoring and managing frailty in the context of cardiometabolic health.