Association of cardiovascular-kidney-metabolic syndrome with all-cause and cardiovascular mortality: A prospective cohort study

Abstract

Background

Given evidence on the cardiovascular disease (CVD) risk conferred by comorbidity risk factors, the American Heart Association (AHA) recently introduced a novel staging construct, named cardiovascular-kidney-metabolic (CKM) syndrome. This study examined the association of CKM syndrome stages with all-cause and cardiovascular mortality among US adults.

Methods

Data were from the National Health and Nutrition Examination Survey (NHANES) 1999–2018 at baseline linked to the 2019 National Death Index records. For each participant, the CKM syndrome was classified into five stages: stage 0 (no CKM risk factors), 1 (excess or dysfunctional adiposity), 2 (metabolic risk factors and chronic kidney disease), 3 (subclinical CVD), or 4 (clinical CVD). The main outcomes were all-cause and cardiovascular mortality.

Results

Among 34,809 participants (mean age: 46.7 years; male: 49.2 %), the prevalence of CKM stages 0 to 4 was 13.2 %, 20.8 %, 53.1 %, 5.0 %, and 7.8 %, respectively. During a median follow-up of 8.3 years, compared to participants with CKM stage 0, those with higher stages had increased risks of all-cause mortality (stage 2: HR 1.43, 95 % 1.13–1.80; stage 3, HR 2.75, 95 % CI 2.12–3.57; stage 4, HR 3.02, 95 % CI 2.35–3.89). The corresponding hazard ratios (95 % confidence interval) of cardiovascular mortality risks were 2.96 (1.39–6.30), 7.60 (3.50–16.5), and 10.5 (5.01–22.2). The population-attributable fractions for advanced (stages 3 or 4) vs. CKM syndrome stages (stages 0, 1, or 2) were 25.3 % for all-cause mortality and 45.3 % for cardiovascular mortality.

Conclusion

Higher CKM syndrome stages were associated with increased risks of all-cause and cardiovascular mortality. These findings emphasize that primordial and primary prevention efforts on promoting CKM health should be strengthened to reduce mortality risk.