Variations in Single-Point Insulin Sensitivity Estimator Index and the Risk of Cardiovascular Disease in Individuals With Cardiovascular-Kidney-Metabolic Syndrome Stages 0 to 3: A National Longitudinal Cohort Study.

BACKGROUND: Prior studies have focused exclusively on baseline single-point insulin sensitivity estimator (SPISE) index levels, and the prognostic impact of longitudinal SPISE index trajectories on incident cardiovascular disease (CVD) remains unclear, particularly among individuals with cardiovascular-kidney-metabolic syndrome stages 0 to 3. This study investigated the prognostic value of dynamic SPISE index changes for CVD risk in this preclinical population. METHODS: This prospective cohort study used data from the CHARLS (China Health and Retirement Longitudinal Study). The SPISE index was calculated using body mass index, triglycerides, and high-density lipoprotein cholesterol. We assessed longitudinal SPISE trajectories and cumulative SPISE index exposure by comparing measurements from wave 1 (baseline) and wave 3. Multivariable Cox proportional hazards models were used to evaluate associations of baseline, cumulative, and dynamic SPISE index profiles with incident CVD risk among participants at cardiovascular-kidney-metabolic stages 0 to 3. RESULTS: The longitudinal cohort comprised 7982 participants, and the cumulative exposure subcohort included 5288 participants. Compared with those with persistently high SPISE index, participants with SPISE index deterioration from high to low had significantly elevated CVD risk (hazard ratio [HR], 1.28 [95% CI, 1.06-1.53]), similar to those with a persistently low SPISE index (HR, 1.36 [95% CI, 1.18-1.56]). Participants in the highest tertiles of baseline and cumulative SPISE index had 22% and 29% lower CVD risk, respectively, with significant effect modification by sex. CONCLUSIONS: Among individuals in cardiovascular-kidney-metabolic syndrome stages 0 to 3, both baseline and cumulative SPISE indices are independently and inversely associated with incident CVD risk, with this protective effect being particularly pronounced in men.