Key result
Higher CHG-CVAI index is linked to ~2.1-fold higher incident CVD risk in early CKM syndrome.
Why the study?
The early stages 0–3 of cardiovascular–kidney–metabolic syndrome represent a critical window for CVD prevention, and although insulin resistance is a key driver of CVD risk, systematic comparisons of insulin resistance surrogates in CVD remain limited.
Do baseline insulin resistance surrogates predict incident cardiovascular disease in adults with stages 0–3 cardiovascular–kidney–metabolic syndrome?
Cohort (n=5,625)
No
Do baseline insulin resistance surrogates predict incident cardiovascular disease in adults with stages 0–3 cardiovascular–kidney–metabolic syndrome?
Simple, low-cost insulin resistance surrogates—particularly the composite index CHG-CVAI—are independently associated with long-term incident cardiovascular disease and modestly improve risk reclassification in adults with early-stage (stages 0–3) CKM syndrome.
CHG-CVAI may refine CVD risk stratification in early CKM syndrome; hypothesis-generating and requires prospective validation before clinical adoption.
Background The early stages 0–3 of cardiovascular–kidney–metabolic (CKM) syndrome represent a critical window for cardiovascular disease (CVD) prevention. Although insulin resistance (IR) is a key driver of CVD risk, systematic comparisons of IR surrogates in CVD remain limited. This study examined the associations of 12 IR surrogates with CVD in participants with stages 0–3 CKM syndrome. Methods This prospective study included 5,625 participants with stages 0–3 CKM syndrome from the Qingdao Diabetes Program. Twelve IR surrogates related to CVD were evaluated using multivariable-adjusted Cox models, restricted cubic splines, sensitivity analyses, and predictive performance analyses, such as triglyceride–glucose index, atherogenic index of plasma, cardiometabolic index, metabolic score for IR (METS-IR), cholesterol-high-density lipoprotein-glucose (CHG) index, CHG plus body mass index, CHG plus waist circumference, CHG plus waist-to-height ratio, CHG plus body roundness index, CHG plus weight-adjusted waist index, CHG plus A body shape index, and CHG plus Chinese visceral adiposity index (CVAI). Results Over a median follow-up of 15.2 years, 1,407 incident CVD events occurred. In multivariable-adjusted analyses, all 12 IR surrogates were significantly associated with CVD risk (all P < 0.05), of CHG-CVAI showing the best performance (Q4 vs. Q1: HR = 2.10, 95% CI = 1.74–2.52). Most indices showed nonlinear dose–response relationships. The associations were higher risk for adults aged <60 years and urban residents as compared with counterparts, and sensitivity analyses confirmed the robustness of the primary findings. Furthermore, addition of each IR surrogate improved CVD risk prediction: C-index ranging from 0.669 to 0.674, NRI ranging from 0.089 to 0.205 and IDI ranging from 0.0004 to 0.0032 (all P < 0.001). Conclusion All IR surrogates, particularly CHG-CVAI were independently associated with incident CVD in early-stages CKM syndrome. These simple, low-cost indices improved risk stratification and moderately identify CVD individuals in high risk population.
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Li et al. (2026) conducted a cohort in Early-stage cardiovascular-kidney-metabolic (CKM) syndrome (stages 0-3) (n=5,625). Insulin resistance surrogates (specifically CHG-CVAI index, highest quartile Q4) vs. Lowest quartile (Q1) of CHG-CVAI index was evaluated on Incident cardiovascular disease (first occurrence of a major cardiac event or stroke) (HR 2.10, 95% CI 1.74-2.52, p=<0.001). Higher levels of the CHG-CVAI insulin resistance index (Q4 vs Q1) were associated with double the risk of incident CVD in early-stage CKM syndrome (HR 2.10, 95% CI 1.74-2.52).
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