Abstract
Background
Heart 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.Objectives
To 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.Methods
This 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.Results
Over 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 Conclusions
Longitudinal 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.