TITLE:
Association between the Single-Point Insulin Sensitivity Estimator and Future Cardiovascular Disease Risk in a Population with Cardiovascular-Kidney-Metabolic Syndrome Stage 0 - 3: A Nationwide Prospective Cohort Study
AUTHORS:
Yuhuan Li, Junli Xue
KEYWORDS:
SPISE, Cardiovascular-Kidney-Metabolic Syndrome, CVD
JOURNAL NAME:
Journal of Biosciences and Medicines,
Vol.14 No.6,
June
16,
2026
ABSTRACT: Objective: The concept of cardiovascular-kidney-metabolic (CKM) syndrome has been proposed to highlight the complex interplay among metabolic disorders, kidney disease, and cardiovascular disease (CVD). We investigated the association between the single-point insulin sensitivity estimator (SPISE), an insulin resistance (IR) marker, and future CVD risk in individuals with CKM stages 0 - 3. Method: Based on data from the China Health and Retirement Longitudinal Study (CHARLS), a total of 6887 participants were included. Kaplan Meier analysis and multivariable Cox proportional hazards models were used to evaluate the association between the SPISE and the CVD incidence. Restricted cubic spline (RCS) models were applied to explore potential non-linear relationships. Subgroup analyses were performed to assess consistency across subgroups. Results: Over a median follow-up of 6.7 years, 1453 CVD events occurred. Higher SPISE was independently associated with lower CVD risk (HR 0.95, 95% CI 0.92 - 0.97). Participants in the highest quartile (Q4) had a 28% lower risk versus the lowest (Q1) (HR 0.72, 95% CI 0.61 - 0.85). RCS showed a linear negative dose–response relationship. Notably, significant interactions were observed for sex (P = 0.021), indicating that the protective association was more robust in men. Conclusions: Higher SPISE levels are significantly associated with reduced CVD risk in CKM stages 0 - 3. SPISE may serve as a valuable marker for early risk identification in these populations.