EClinicalMedicine. 2026 Aug 22;99:104155. doi: 10.1016/j.eclinm.2026.104155. eCollection 2026 Sep.
ABSTRACT
BACKGROUND: The cardiovascular-kidney-liver-metabolic (CKLM) framework represents the multi-organ interplay of systemic metabolic disorders that drive the global burden of cardiovascular diseases (CVD).
METHODS: This study is a descriptive epidemiological analysis of the Global Burden of Disease Study 2023 that examines the trends in mortality and disability-adjusted life years (DALYs) associated with atherosclerotic CVD, chronic kidney disease (CKD), type 2 diabetes (T2D), obesity and metabolic dysfunction-associated steatotic liver disease (MASLD), from 1990 to 2023, across 204 countries and territories. Epidemiological trends were stratified by age, sex, region, and sociodemographic index (SDI).
FINDINGS: In 2023, the global CKLM burden contributed to 626.7 million DALYs, with an age-standardized DALY rate of 6944.3 per 100,000 population. Atherosclerotic CVD was the largest contributor to the CKLM burden (3924.2 [95% Uncertainty Interval {UI}: 3666.9-4181.4]), followed by obesity (1500.0 [95% UI: 730.4-2206.5]), T2D (956.7 [95% UI: 794.4-1142.4]), CKD (523.8 [95% UI: 468.0-590.1]), and MASLD (39.6 [95% UI: 31.2-49.9]). From 1990 to 2023, CKLM-related age-standardized DALYs fell 24.4%, primarily driven by improvements in atherosclerotic CVD (41.5% decrease), while rapid increases were seen in T2D (37.5% increase) and obesity (23.3% increase). Disparities in CKLM burden exist across SDI, geography, and age-sex categories.
INTERPRETATION: Improvements in the global CKLM burden, driven by gains in CVD prevention, are offset by the rising burden of upstream CKLM drivers including obesity, T2D, CKD and MASLD. Population-focused strategies for prevention need to target shared risk factors driving the CKLM syndemic to achieve the greatest reduction in overall morbidity and mortality.
FUNDING: This research was supported by the NMRC Research Transition Award and the CSDU Clinician-Scientist Grant.
PMID:42668515 | PMC:PMC13524663 | DOI:10.1016/j.eclinm.2026.104155