Eur J Intern Med. 2026 Sep 18:107197. doi: 10.1016/j.ejim.2026.107197. Online ahead of print.
ABSTRACT
Cardiovascular-kidney-metabolic (CKM) syndrome was formalized by the American Heart Association in 2023 to capture the biological and clinical continuum linking excess adiposity, metabolic dysfunction, chronic kidney disease (CKD), and cardiovascular disease (CVD). Population-based studies indicate that CKM stage ≥1 affects approximately three-quarters to nine-tenths of adults in contemporary cohorts, with stage 2 consistently representing the largest population reservoir. Importantly, CKM distribution is not uniform: advanced stages rise sharply with age and are more frequent in men and socioeconomically disadvantaged groups. Beyond its high prevalence, CKM staging carries substantial prognostic information. Longitudinal studies from the United States, Europe, and Asia demonstrate a graded increase in cardiovascular and all-cause mortality with advancing CKM stage, while emerging evidence links CKM multimorbidity to kidney failure, heart-failure hospitalization, frailty, impaired quality of life, and higher healthcare expenditure. This burden is expected to increase further as obesity, diabetes, CKD, and heart failure expand globally, with Global Burden of Disease analyses projecting substantial increases in the absolute burden of major CKM components through 2046. The 2026 AHA/ACC/ADA/ASN multisociety CKM guideline now translates this epidemiological framework into clinical practice through integrated staging, kidney assessment, and absolute-risk-based prevention. Major evidence gaps remain in stage transitions and regression, patient-reported outcomes, health economics, and low- and middle-income countries. For these reasons, this review aims to summarize the evolving epidemiology of CKM syndrome, examine its clinical implications, and outline its projected future burden and key priorities for research and clinical practice.
PMID:42760144 | DOI:10.1016/j.ejim.2026.107197