Abstract

Background Cardiovascular-kidney-metabolic (CKM) syndrome is a new concept proposed by the American Heart Association (AHA) that emphasizes the complex relationship between kidney disease, heart disease and metabolic factors. Many studies have shown that insulin resistance (IR) in CKM syndrome stages 0-3 is associated with the occurrence of cardiovascular disease (CVD); however, the impact of physical exercise on this process remains unclear.
Methods We enrolled 3,048 patients with CKM syndrome stages 0-3 from the China Health and Retirement Longitudinal Study (CHARLS) during its follow-up period from 2011 to 2020. The primary outcome was the incidence of CVD. Estimated glucose disposal rate (eGDR) was used as an evaluation index for IR, and metabolic equivalents (MET) score was used as an evaluation index for physical activity (PA). Cox regression analysis, restricted cubic spline (RCS) curve, Kaplan-Meier (K-M) survival curve, interaction and subgroup analyses were used to comprehensively evaluate the association between IR and PA with the incidence of CVD. Simultaneously, we performed mediation analysis to evaluate the mediating effects of high eGDR, low eGDR and PA on CVD.
Results During 2011-2020, 731 (23.98%) individuals developed CVD. Low eGDR and MET scores were independent risk factors for CVD. In model 3, the hazard ratio (HR) of the high eGDR group was 0.78 (95% confidence interval [CI] 0.62-0.98), and the HR of the high PA group was 0.78 (95% CI 0.67-0.91). Compared with individuals with low eGDR and low PA levels, individuals with high eGDR and high PA levels showed a significantly lower incidence of CVD, with a HR of 0.63 (95% CI 0.48-0.83). The RCS curves showed a negative linear correlation with CVD, and no significant interaction between them was observed. However, we found a mediating effect of PA on the relationship between eGDR and CVD, particularly in the low eGDR group.
Conclusions In participants with CKM syndrome stages 0-3, eGDR and PA had a common effect on the occurrence of CVD. PA played a mediating role between eGDR and CVD, especially in the low eGDR group, suggesting the necessity of guiding patients with insulin resistance to engage in physical exercise.