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Research Article: Geriatric nutritional risk Index predicts adverse outcomes across cardiovascular–kidney–metabolic syndrome: discovery in NHANES and external validation in CKM stage 4 patients undergoing PCI

Date Published: 2026-07-07

Abstract:
Cardiovascular–kidney–metabolic (CKM) syndrome imposes a high burden of adverse events, yet prognostic biomarkers remain scarce. We evaluated the prognostic value of the Geriatric Nutritional Risk Index (GNRI) across CKM stages 1–4 and in high-risk patients undergoing percutaneous coronary intervention (PCI). This discovery–validation study utilized 16,074 adults with CKM syndrome from NHANES (1999–2018) and an external validation cohort of 2,401 CKM Stage 4 patients undergoing PCI. Primary outcomes were all-cause mortality (discovery) and major adverse cardiovascular events (MACE; validation). In the discovery cohort, compared with the highest GNRI quartile (Q4), Q1 was associated with significantly higher hazards of all-cause (HR 1.58; 95% CI 1.32–1.89) and cardiovascular mortality (HR 2.13; 95% CI 1.55–2.93); each 1-unit increase in GNRI was associated with a lower hazard of all-cause mortality (HR 0.95; 95% CI 0.94–0.97). In the validation cohort, Q1 vs. Q4 conferred a markedly increased risk of MACE (HR 2.52; 95% CI 2.03–3.13), with each 1-unit increase in GNRI associated with a lower risk of MACE (HR 0.95; 95% CI 0.94–0.96). Restricted cubic splines revealed a non-linear inverse relationship, with risk rising sharply below GNRI???100. Adding GNRI to a base clinical model significantly improved Harrell's C-index for MACE (? +0.048, P <?0.001) with excellent calibration. Lower GNRI is independently associated with adverse outcomes across the CKM spectrum. In an external CKM Stage 4 PCI cohort, GNRI provided clinically meaningful incremental risk discrimination, supporting its use as an inexpensive marker to help identify higher-risk patients. Whether GNRI-guided management improves outcomes remains to be determined.

Introduction:
Cardiovascular–kidney–metabolic (CKM) syndrome imposes a high burden of adverse events, yet prognostic biomarkers remain scarce. We evaluated the prognostic value of the Geriatric Nutritional Risk Index (GNRI) across CKM stages 1–4 and in high-risk patients undergoing percutaneous coronary intervention (PCI).

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