Advanced cardiovascular-kidney-metabolic (CKM) syndrome (stages 3 and 4) is associated with higher risks of all-cause and cardiovascular (CV) mortality at 20 years, according to a prospective study in Hong Kong.
In 2023, the American Heart Association introduced a five-stage framework for CKM syndrome, ranging from absence of CKM risk factors (stage 0) to established CV disease (stage 4). To analyze the prospective associations of CKM stages with mortality outcomes and how CKM syndrome progresses over time, researchers from the University of Hong Kong conducted a prospective study using data from the Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS). [J Am Heart Assoc 2026;15:e044588]
CKM syndrome highly prevalent in HK
A total of 1,912 community-dwelling Chinese participants (mean age, 52.5 years; male, 46.3 percent) who underwent health assessment in 2000–2004 were followed for over 20 years.
“CKM syndrome [stage ≥1] is highly prevalent among the Chinese population,” noted the researchers. At baseline, prevalence was 74.9 percent among participants aged <40 years, 84.4 percent among aged 40–55 years, 94.3 percent among those those aged 55–65 years, and 97.4 percent among those aged ≥65 years.
CKM stages 3 & 4: Higher risk of death from 15 years onward
At 15 and 20 years, 148 and 275 deaths were recorded, respectively. There were 37 CV deaths and 238 non-CV deaths at 20 years, including infection, end-stage kidney disease, and cancer.
“Our study provided insights about the prognostic impact of advanced CKM syndrome on mortality outcomes,” commented the researchers.
At 15 years, CKM syndrome stages 3 and 4 were associated with a higher risk of all-cause mortality (stage 3: hazard ratio [HR], 4.5; 95 percent confidence interval [CI], 1.7–11.9; p=0.002; stage 4: HR, 4.1; 95 percent CI, 1.4–12.1; p=0.012) vs stage 0.
At 20 years, CKM syndrome stages 3 and 4 were associated with higher risks of both all-cause mortality (stage 3: HR, 3.8; 95 percent CI, 1.8–7.9; p<0.001; stage 4: HR, 3.7; 95 percent CI, 1.6–8.3; p=0.002) and CV death (stage 3: HR, 17.4; 95 percent CI, 2.3–133; p=0.006; stage 4: HR, 21.4; 95 percent CI, 2.5–187.3; p=0.006) vs stage 0.
“Notably, the association between CKM syndrome stages and all-cause death at 20 years was more readily observed among women than men,” pointed out the researchers.
Progressive trajectory over time
Individuals initially at lower CKM stages may progress to more advanced stages over time. The prevalence of advanced CKM syndrome stages 3 and 4 increased from 5.9 and 1.8 percent at follow-up in 2000–2004 to 17.8 and 6.2 percent in 2016–2018, respectively.
CKM syndrome stage 2, older age of ≥55 years, and chronic smoking at baseline were significantly associated with a higher risk of progression to advanced CKM stages (all p<0.05).
“Our study underscores the importance of early screening and staging of CKM syndrome to prevent disease progression and reduce mortality risk,” commented the researchers.