ArticleCardiovascular diabetology2026
Longitudinal inflammatory-metabolic-adiposity burden and incident heart failure across cardiovascular-kidney-metabolic stages: a prospective cohort study.
Article in Cardiovascular diabetology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundHeart failure remains a major health burden among older adults. Although systemic inflammation, metabolic dysregulation, and central adiposity are individually recognized as heart failure risk factors, composite biomarkers capturing their longitudinal convergence and interaction with cardiovascular-kidney-metabolic (CKM) staging remain unexplored.
objectivesTo investigate the association of longitudinal CTGW composite index (C-reactive protein × triglyceride-glucose index × waist-to-height ratio) trajectories and cumulative burden with incident heart failure, and to examine effect modification by baseline CKM stage.
methodsThis prospective cohort study included 1946 participants aged 50 years and older from the English Longitudinal Study of Ageing, free of heart failure at Wave 2 (2004-2005), followed through Wave 8 (2016-2017). Group-based multi-trajectory modeling jointly classified longitudinal CRP, triglycerides, glucose, and WHtR across three waves. Cumulative CTGW burden was quantified using the trapezoidal rule. Cox proportional hazards regression with sequential adjustment and restricted cubic spline analyses were employed.
resultsOver a median follow-up spanning 12 years, 113 participants (5.8%) developed incident heart failure. Three distinct trajectories were identified: low-stable (n = 697, 35.8%), moderate-metabolic (n = 943, 48.5%), and high-inflammatory (n = 306, 15.7%). In fully adjusted models, the high-inflammatory trajectory conferred the greatest risk (HR = 2.69, 95% CI 1.46-4.93, P = 0.001), followed by the moderate-metabolic trajectory (HR = 1.96, 95% CI 1.17-3.29, P = 0.011). For cumulative burden, the highest quartile was significantly associated with incident heart failure (HR = 2.35, 95% CI 1.31-4.24, P = 0.004; P for trend < 0.001), with each standard deviation increase corresponding to 19% higher risk (HR = 1.19, 95% CI 1.04-1.36, P = 0.014). A nonlinear dose-response relationship was confirmed (P for nonlinearity = 0.032), with the risk threshold identified at approximately 8.2. Stratified analyses revealed significant effect modification by CKM stage (P for interaction = 0.031), with the strongest association observed in Stage 3-4 (HR = 2.37, 95% CI 1.24-4.53, P = 0.009). Subgroup analyses demonstrated consistent effect directions across age, sex, BMI, and comorbidity strata without significant interactions.
conclusionsLongitudinal CTGW trajectories and cumulative burden are independently associated with incident heart failure in a nonlinear dose-response manner, with the association amplified across advancing CKM stages, supporting the CTGW composite index as a potential integrative biomarker for heart failure risk stratification.
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