Combined and progressive effect of frailty and sarcopenia on the risk of cardiovascular disease in middle-aged and older adults.

Background: Frailty and sarcopenia are two related conditions, but how they lead to cardiovascular disease (CVD) remain unclear. The study aimed to investigate the combined and progressive effect of them. Methods: The data were from China Health and Retirement Longitudinal Study (CHARLS). Frailty status was evaluated by the Rockwood frailty index and sarcopenia status was classified according to the Asia Working Group for Sarcopenia 2019. Results: A total of 7187 participants aged over 45 years (49.41% male; mean age 57.38 ± 8.41 years) were enrolled in 2011. Among them, 4265 individuals without CVD events between 2011 and 2015 were included in the analysis of dynamic changes. Over the nine-year period, both frailty and sarcopenia status were independently associated with an increased risk of CVD. A significant interaction for CVD was observed between frailty and sarcopenia status (P for interaction <0.001). Furthermore, the coexistence of frailty and sarcopenia was associated with the highest risk of incident CVD (hazard ratios (HR) = 2.18; 95% confidence interval (CI) = 1.81-2.62), indicating that individuals with both conditions had more than double the risk of developing CVD, highlighting a substantially elevated cardiovascular vulnerability. Additionally, frailty was found to statistically mediate approximately 35.38% of the association between sarcopenia and CVD. Regarding dynamic changes, individuals who remained frail or experienced worsening sarcopenia were associated with the highest incidence of CVD, with HRs of 3.29 (95% CI = 2.44-4.45) and 1.56 (95% CI = 1.28-1.90), respectively, compared to those who remained robust or non-sarcopenic. These findings indicate that persistent frailty and deteriorating muscle health substantially increase CVD risk. Conclusions: The study indicated there was a combined and progressive effect of frailty and sarcopenia on CVD. These findings highlighted the importance of identifying and improving sarcopenia and frailty.