Associations of Cardiovascular-Kidney-Metabolic Syndrome With All-Cause and Cardiovascular Death and the Progression of Cardiovascular-Kidney-Metabolic Syndrome Among Hong Kong Chinese People Over 2 Decades.
Lanlan Li, D. Lui, et al. • Journal of the American Heart Association : Cardiovascular and Cerebrovascular Disease • 2026
Advanced cardiovascular-kidney-metabolic (CKM) syndrome stages 3 and 4 were associated with significantly higher risks of all-cause and cardiovascular mortality over 20 years, and CKM stage 2 at baseline was associated with nearly 4-fold higher odds of progression to advanced CKM stages.
Key Findings
Results
At baseline, the majority of participants had CKM stage 2, with a small proportion at advanced stages 3 and 4.
Total of 1912 eligible participants were included (mean age 52.5±12.0 years; 46.3% men).
Data came from the Hong Kong CRISPS 2 population-based cohort of community-dwelling Chinese participants assessed between 2000 and 2004.
Participants were followed for 20 years.
Results
CKM stages 3 and 4 were each associated with approximately 3.7–3.8 times higher risk of all-cause mortality compared to lower stages.
Adjusted hazard ratio for CKM stage 3 and all-cause mortality: 3.8 (95% CI, 1.8–7.9; P<0.001).
Adjusted hazard ratio for CKM stage 4 and all-cause mortality: 3.7 (95% CI, 1.6–8.3; P=0.002).
Cox proportional hazards regression models were used to evaluate these associations.
Follow-up period was 20 years.
Results
CKM stages 3 and 4 were associated with dramatically higher risks of cardiovascular mortality, with hazard ratios exceeding 17 and 21, respectively.
Adjusted hazard ratio for CKM stage 3 and cardiovascular mortality: 17.4 (95% CI, 2.3–133.0; P=0.006).
Adjusted hazard ratio for CKM stage 4 and cardiovascular mortality: 21.4 (95% CI, 2.5–187.3; P=0.006).
Wide confidence intervals for cardiovascular mortality reflect the relatively small number of participants at stages 3 and 4 (149 and 40, respectively).
These associations were observed over a 20-year follow-up period.
Results
Among participants at early CKM stages 0–2, baseline CKM stage 2 was significantly associated with a nearly 4-fold higher odds of progressing to advanced CKM stages 3 or 4.
Odds ratio for CKM stage 2 at baseline predicting progression to stages 3 or 4: 3.9 (95% CI, 2.3–6.7; P<0.001).
Comparison was made relative to participants with no CKM (stage 0) at baseline.
Analysis was restricted to participants at early CKM stages 0 to 2 at baseline.
Progression was assessed over the 20-year follow-up period.
Methods
The study used the 2023 American Heart Association CKM syndrome staging framework applied to a prospective Chinese population cohort over two decades.
The American Heart Association established CKM syndrome and defined its stages in 2023.
The study is observational, using the Hong Kong CRISPS 2 cohort.
Participants were community-dwelling Chinese individuals who underwent comprehensive health assessment between 2000 and 2004.
Cox proportional hazards regression models were used for mortality analyses.
What This Means
This research suggests that people with more advanced stages of a newly defined health condition called cardiovascular-kidney-metabolic (CKM) syndrome — which combines problems with the heart, kidneys, and metabolism (such as diabetes and obesity) — face dramatically higher risks of dying from any cause or from heart disease over a 20-year period. The study followed nearly 2,000 adults in Hong Kong from the early 2000s and found that those at the most advanced CKM stages (stages 3 and 4) were about 3.7 to 3.8 times more likely to die from any cause and roughly 17 to 21 times more likely to die from cardiovascular causes compared to those at lower stages.
The study also found that even people at an intermediate stage (stage 2, which was the most common stage — affecting 65% of participants) were nearly four times more likely to progress to the dangerous advanced stages compared to those with no CKM syndrome at baseline. This suggests that CKM syndrome tends to worsen over time and that catching it at an earlier, more treatable stage may be important.
This research matters because CKM syndrome was only formally defined by the American Heart Association in 2023, and this study provides some of the first long-term evidence — spanning two decades — about how dangerous the advanced stages can be and how the condition progresses. The findings highlight the potential value of early screening and staging of CKM syndrome in order to intervene before the condition advances to life-threatening levels.
Lanlan Li, D. Lui, C. Fong, J. Mak, Chloe Yu-Yan Cheung, Aimin Xu, et al.. (2026). Associations of Cardiovascular-Kidney-Metabolic Syndrome With All-Cause and Cardiovascular Death and the Progression of Cardiovascular-Kidney-Metabolic Syndrome Among Hong Kong Chinese People Over 2 Decades.. Journal of the American Heart Association : Cardiovascular and Cerebrovascular Disease. https://doi.org/10.1161/JAHA.125.044588