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Background <p>Cardiovascular-kidney-metabolic (CKM) syndrome reflects the interaction of metabolic disorders with organ dysfunction. Cardiovascular disease (CVD) is a common consequence. Visceral adiposity is an important contributor to this pathway, but its impact in early CKM and the possible mediation through arterial stiffness are not well clarified.</p> Methods <p>A total of 6,715 Chinese adults (≥ 45 years) at CKM stages 0–3 was selected from the China Health and Retirement Longitudinal Study. Using Cox proportional hazards regression together with restricted cubic spline (RCS) models, this nationwide prospective cohort study investigated the links between CVD and six visceral fat indices, namely triglyceride-glucose waist-to-height ratio (TyG-WHtR), relative fat mass (RFM), weight-adjusted waist index (WWI), conicity index (CI), body roundness index (BRI), and Chinese visceral adiposity index (CVAI). Causal mediation analysis was applied to evaluate the potential mediation by arterial stiffness, as reflected by estimated pulse wave velocity (ePWV). Subgroup and sensitivity analyses were conducted to confirm the stability of the results.</p> Results <p>Across the 9-year follow-up, 1,606 individuals developed new-onset CVD. In the model with full adjustment, RFM (HR = 1.46, 95% CI: 1.31–1.62) exhibited the strongest associations. The highest quartiles of CVAI and TyG-WHtR were associated with significantly increased CVD risk, with HRs of 2.26 (95% CI: 1.95–2.62) and 1.81 (95% CI: 1.56–2.11), respectively. In RCS analysis, TyG-WHtR, RFM, WWI, BRI and CVAI showed linear associations, while CI exhibited nonlinear patterns. ePWV partially mediated these associations, accounting for 12.18–22.14% of the total effect. The results were consistent in subgroup and sensitivity analyses.</p> Conclusion <p>These results demonstrate a significant association between six visceral fat indices and CVD risk, which is partially mediated by arterial stiffness, highlighting the potential of these indices, particularly CVAI, to serve as accessible biomarkers for early CVD detection among individuals at CKM stages 0–3.</p>

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Associations of visceral fat accumulation with cardiovascular disease across cardiovascular-kidney-metabolic syndrome stages 0–3: mediation effects of arterial stiffness in a prospective cohort study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月25日

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  • Ke Wang,
  • Xinyao Luo,
  • Dingyuan Wan,
  • Baihai Su,
  • Yupei Li

摘要

Background

Cardiovascular-kidney-metabolic (CKM) syndrome reflects the interaction of metabolic disorders with organ dysfunction. Cardiovascular disease (CVD) is a common consequence. Visceral adiposity is an important contributor to this pathway, but its impact in early CKM and the possible mediation through arterial stiffness are not well clarified.

Methods

A total of 6,715 Chinese adults (≥ 45 years) at CKM stages 0–3 was selected from the China Health and Retirement Longitudinal Study. Using Cox proportional hazards regression together with restricted cubic spline (RCS) models, this nationwide prospective cohort study investigated the links between CVD and six visceral fat indices, namely triglyceride-glucose waist-to-height ratio (TyG-WHtR), relative fat mass (RFM), weight-adjusted waist index (WWI), conicity index (CI), body roundness index (BRI), and Chinese visceral adiposity index (CVAI). Causal mediation analysis was applied to evaluate the potential mediation by arterial stiffness, as reflected by estimated pulse wave velocity (ePWV). Subgroup and sensitivity analyses were conducted to confirm the stability of the results.

Results

Across the 9-year follow-up, 1,606 individuals developed new-onset CVD. In the model with full adjustment, RFM (HR = 1.46, 95% CI: 1.31–1.62) exhibited the strongest associations. The highest quartiles of CVAI and TyG-WHtR were associated with significantly increased CVD risk, with HRs of 2.26 (95% CI: 1.95–2.62) and 1.81 (95% CI: 1.56–2.11), respectively. In RCS analysis, TyG-WHtR, RFM, WWI, BRI and CVAI showed linear associations, while CI exhibited nonlinear patterns. ePWV partially mediated these associations, accounting for 12.18–22.14% of the total effect. The results were consistent in subgroup and sensitivity analyses.

Conclusion

These results demonstrate a significant association between six visceral fat indices and CVD risk, which is partially mediated by arterial stiffness, highlighting the potential of these indices, particularly CVAI, to serve as accessible biomarkers for early CVD detection among individuals at CKM stages 0–3.