Associations of composite metabolic indices with adverse outcomes in stage 0–3 cardiovascular-kidney-metabolic syndrome: a scoping review and evidence map

Abstract

Background

Stage 0–3 of cardiovascular-kidney-metabolic (CKM) syndrome represents a critical window for primary prevention, yet the prognostic value of numerous composite metabolic indices derived from routine clinical and laboratory parameters in this population remains unclear. We mapped the available evidence and assessed the direction, consistency, and certainty of associations.

Methods

Following PRISMA-ScR guidelines, we searched PubMed, Web of Science, Scopus, and the Cochrane Library from inception to 15 July 2026. We included prospective cohort studies that reported multivariable-adjusted hazard ratios for any composite metabolic index against all-cause mortality (ACM), cardiovascular mortality (CVM), incident cardiovascular disease (iCVD), coronary heart disease (CHD), stroke, cardiometabolic multimorbidity (CMM), heart failure (HF), or chronic kidney disease (CKD) progression in adults with stage 0–3 CKM. Two reviewers independently screened records, extracted data, assessed risk of bias using Quality In Prognosis Studies (QUIPS), and performed an exploratory GRADE appraisal. No meta-analysis was conducted due to substantial heterogeneity.

Results

We included 34 study reports, predominantly derived from the China Health and Retirement Longitudinal Study (CHARLS). TyG-family indices accounted for over 45% of evaluated exposures. The evidence landscape was heavily concentrated on iCVD, whereas no eligible prospective study evaluated HF or CKD progression as a primary endpoint. In within-study comparisons, TyG-WC and TyG-WHtR most frequently demonstrated stronger adjusted associations with adverse outcomes than the basal TyG index; conversely, eGDR consistently showed inverse associations. Most studies were classified as having a moderate risk of bias, primarily driven by unvalidated outcome ascertainment and residual confounding. Exploratory GRADE appraisal rated the vast majority of index-outcome pairs as low or very low certainty.

Conclusion

In stage 0–3 CKM, TyG-WC and TyG-WHtR showed the most consistent associations with adverse outcomes in within-study comparisons, whereas eGDR was predominantly inversely associated. However, overall evidence certainty remains low, and critical gaps persist for HF and CKD progression. Future research must shift from index proliferation to external validation against PREVENT and prospective adjudication of hard endpoints.

Research insights

What is currently known about this topic?

Numerous composite metabolic indices have been proposed as surrogates for insulin resistance and adiposity, but their comparative prognostic value in CKM stages 0–3 remains uncharted.

What is the key research question?

Which composite metabolic indices demonstrate the most robust and consistent associations with adverse outcomes in CKM stages 0–3, and what are the critical evidence gaps?

What is new?

This is the first scoping review and evidence map covering the full spectrum of composite metabolic indices in CKM stages 0–3. In within-study comparisons, TyG-WC and TyG-WHtR most frequently demonstrated stronger positive associations with adverse outcomes; however, this evidence does not establish predictive superiority or a synergistic biological mechanism. Crucially, no eligible prospective study evaluated HF or CKD progression as a primary endpoint, highlighting a mismatch between the current evidence base and the 2026 AHA/ACC/ADA/ASN guideline priorities. Furthermore, exploratory GRADE appraisal indicates that the vast majority of these associations remain of low or very low certainty.

How might this study influence clinical practice?

TyG-WC and TyG-WHtR represent promising, low-cost tools for early risk stratification in CKM. However, their clinical adoption requires rigorous external validation across diverse ancestries and direct benchmarking against the PREVENT equations. To bridge the current evidence gaps, future research must prioritize the prospective adjudication of hard heart failure and renal endpoints, shifting the paradigm from mere index proliferation toward demonstrating tangible incremental value.