Prevalence and mortality of cardiovascular-kidney-metabolic syndrome in US adults, 1999–2018

Cardiovascular-kidney-metabolic (CKM) syndrome is a novel staging construct that reflects the pathophysiological interplay between these individual conditions. The long-term trends in the prevalence of CKM syndrome in the US have not been well characterized. This serial cross-sectional study used data from the National Health and Nutrition Examination Survey (1999–2018) to define CKM stages from 0 (no risk factors) to 4 (clinical CVD). Participants younger than 20 years, pregnant patients, and those with missing mortality data and NHANES fasting subsample weights were excluded. We calculated the age- and sex-adjusted prevalence of each stage and its trends. Survey-weighted Cox regression was used to estimate the mortality risk with each stage. The prevalence of CKM syndrome at each stage was as follows: stage 0, 11.9%; stage 1, 24.9%; stage 2, 49.1%; stage 3, 4.6%; and stage 4, 9.5%. The prevalence of CKM stages 0 and 4 decreased between 1999 and 2018, but that of CKM stages 1 and 3 increased. The risk of all-cause and CVD mortality showed a graded increase from stage 1 to 4 compared to stage 0 (HRs for all-cause death in stage 4 = 2.87, 95% CI: 1.98–4.17, and CVD death = 4.68, 95% CI: 1.95–11.26). Nearly 90% of US adults have Stage 1 or higher CKM syndrome, and CKM stage is associated with graded mortality risk. Metabolic abnormalities explain the largest share of the mortality gradient, suggesting that population and clinical strategies focused on metabolic risk reduction should be prioritized to reduce CKM-related mortality. • We examined the prevalence and mortality of cardiovascular-kidney-metabolic (CKM) syndrome stages in US adults between 1999 and 2018. • Almost 90% of US adults had stage 1 or higher CKM syndrome. • The prevalence of CKM stages 0 and 4 decreased between 1999 -2018, but that of CKM stages 1 and 3 increased. • The risk of all-cause and CVD mortality showed a graded increase from stage 1 to 4 compared to stage 0. • Metabolic factors drive most of the excess mortality, highlighting the importance of targeting metabolic risk in prevention and care.