The association of SPISE with cardiometabolic multimorbidity and stroke in middle-aged and older adults: a nationwide prospective cohort study

Insulin resistance is a key driver of cardiometabolic diseases, including stroke. The single-point insulin sensitivity estimator (SPISE) is a novel non-invasive marker of insulin sensitivity calculated from fasting triglycerides, high-density lipoprotein cholesterol and body mass index. However, its association with cardiometabolic multimorbidity (CMM) and stroke in the general population remains unclear. This study aimed to investigate the prospective association between SPISE and incident CMM and stroke in middle-aged and older Chinese adults. This prospective cohort study included 6,624 participants aged 45 years and older from the China Health and Retirement Longitudinal Study (CHARLS) with follow-up through 2020. SPISE was calculated using a validated formula. Cox proportional hazards regression models, restricted cubic spline analyses, Kaplan-Meier survival curves, and subgroup analyses were employed to evaluate the associations between SPISE and incident CMM and stroke. Over a median follow-up of 114 months, 632 participants (9.5%) developed incident stroke, and 696 (10.5%) developed CMM. In fully adjusted multivariable models, each one-unit increase in the baseline SPISE index was significantly associated with a 10% decreased risk of incident stroke (HR = 0.90, 95% CI: 0.86–0.94) and a 15% decreased risk of CMM (HR = 0.85, 95% CI: 0.81–0.89). Compared to the low SPISE reference group (< 6.61), individuals in the high SPISE category (≥ 6.61) exhibited a 27% lower risk of stroke (HR = 0.73, 95% CI: 0.62–0.88) and a 48% lower risk of CMM (HR = 0.52, 95% CI: 0.43–0.62). Restricted cubic spline analyses confirmed strictly linear, inverse dose-response relationships between SPISE and both outcomes. These protective associations remained structurally robust across diverse demographic and clinical subgroups, with significant effect modification identified solely for baseline heart disease and age concerning the CMM outcome. Higher SPISE is independently and linearly associated with reduced risks of incident CMM and stroke in middle-aged and older Chinese adults. As a simple, low-cost marker derived from routine clinical measurements, SPISE may serve as a practical tool for cardiometabolic risk stratification in primary care settings.