Load-capacity index and cardiometabolic risk: a longitudinal meta-analysis

AIMS: The load-capacity index (LCI), defined as the ratio of fat mass to fat-free mass, represents a novel composite biomarker integrating metabolic load and functional capacity. This systematic review and meta-analysis aimed to determine the longitudinal association between LCI and incident cardiometabolic disease risk. METHODS: We systematically searched PubMed, Embase, Web of Science, Cochrane Central, and Scopus from inception through January 2026 for longitudinal cohort studies reporting the association between LCI and cardiometabolic outcomes. Random-effects meta-analysis was performed using the DerSimonian-Laird method. Heterogeneity was assessed using Cochran's Q, τ², and I² statistics. Study-specific log(HR) values and standard errors are reported in the Supplementary Material to enable full reproducibility. RESULTS: Eighteen longitudinal cohort studies comprising 129,777 participants and 5647 cardiometabolic events were included (mean follow-up: 11.4 years). Higher LCI was significantly associated with increased cardiometabolic risk (pooled HR = 1.174, 95% CI: 1.145-1.204; p < 0.0001). There was low between-study heterogeneity (I² = 11.6%; Cochran's Q = 19.22, df = 17, p = 0.3159; τ² = 0.000347). The association was consistent across age groups, sex, and body composition assessment methods (p-interaction > 0.05 for all). LCI provided incremental predictive value beyond established risk factors (NRI: 0.15-0.28; ΔC-statistic: 0.025-0.041). CONCLUSIONS: Higher LCI is independently and consistently associated with increased cardiometabolic disease risk across diverse populations (HR = 1.174, corresponding to a 17.4% increased risk per unit increase). LCI provides clinically meaningful incremental predictive value and warrants consideration as a robust supplementary tool to guide preventive interventions.