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Different Stages of Cardiovascular-Kidney-Metabolic Syndrome Associated With the Risk of All-Cause and Cause-Specific

Xiangyu Wang1, Mengge Yang2, Qunwei Ma2

  • 1College of Public Health, Zhengzhou University, Zhengzhou Henan, 450001, China, zzu.edu.cn.

International Journal of Endocrinology
|August 4, 2026
PubMed

Insights

Individuals with very high-risk chronic kidney disease (CKD) face mortality risks comparable to or greater than those with subclinical cardiovascular disease (CVD). Early intervention is crucial for this high-risk CKD subgroup to mitigate severe health outcomes.

Area of Science:

  • Cardiovascular Science
  • Nephrology
  • Metabolic Syndrome Research

Background:

  • Cardiovascular-Kidney-Metabolic (CKM) syndrome Stage 3, characterized by subclinical cardiovascular disease (CVD), is often diagnosed using risk equivalents due to limited diagnostic tools.
  • A critical question is whether subgroups of Stage 3, specifically high 10-year CVD risk (Stage 3a) and very high-risk CKD (Stage 3b), have comparable mortality risks.

Purpose of the Study:

  • To compare mortality risks between Stage 3a (high 10-year CVD risk) and Stage 3b (very high-risk CKD) within the CKM syndrome framework.
  • To evaluate the prognostic implications of different risk-equivalent classifications in Stage 3 CKM syndrome.

Main Methods:

  • Analysis of 344,515 participants from the UK Biobank and 24,545 from NHANES, stratified by AHA criteria into CKM stages.
  • Cox proportional hazards regression models were used to assess all-cause, cardiovascular, renal, and cancer mortality risks across stages.
  • Stage 3 was subclassified into 3a (high 10-year CVD risk) and 3b (very high-risk CKD).

Main Results:

  • In UK Biobank, Stage 3b (very high-risk CKD) showed the second-highest hazard ratios for all-cause (4.95), cardiovascular (18.75), renal (59.73), and cancer mortality (2.88) compared to Stage 0.
  • Stage 3b mortality risks significantly exceeded those in Stage 3a and even Stage 4a (subclinical CVD without high risk).
  • NHANES cohort analysis validated these findings for all-cause and cardiovascular mortality.

Conclusions:

  • Patients classified as Stage 3b (very high-risk CKD) face substantial mortality risks, even without clinical CVD.
  • These individuals require significant clinical attention and prompt intervention strategies.
  • The findings highlight the critical prognostic importance of very high-risk CKD within CKM syndrome.
Abstract

Keywords:
cardiovascular diseasecardiovascular–kidney–metabolic syndromechronic kidney diseasemortalitystage

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