Scholarlink

Background <p>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.</p> Objectives <p>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.</p> Methods <p>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.</p> Results <p>Over a median follow-up spanning 12 years, 113 participants (5.8%) developed incident heart failure. Three distinct trajectories were identified: low-stable (<i>n</i> = 697, 35.8%), moderate-metabolic (<i>n</i> = 943, 48.5%), and high-inflammatory (<i>n</i> = 306, 15.7%). In fully adjusted models, the high-inflammatory trajectory conferred the greatest risk (HR = 2.69, 95% CI 1.46–4.93, <i>P</i> = 0.001), followed by the moderate-metabolic trajectory (HR = 1.96, 95% CI 1.17–3.29, <i>P</i> = 0.011). For cumulative burden, the highest quartile was significantly associated with incident heart failure (HR = 2.35, 95% CI 1.31–4.24, <i>P</i> = 0.004; P for trend &lt; 0.001), with each standard deviation increase corresponding to 19% higher risk (HR = 1.19, 95% CI 1.04–1.36, <i>P</i> = 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, <i>P</i> = 0.009). Subgroup analyses demonstrated consistent effect directions across age, sex, BMI, and comorbidity strata without significant interactions.</p> Conclusions <p>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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Longitudinal inflammatory-metabolic-adiposity burden and incident heart failure across cardiovascular-kidney-metabolic stages: a prospective cohort study

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月26日

查看全文
  • Fangyi Dai,
  • Yong Dai

摘要

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 < 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.

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.