The global burden of atherosclerotic cardiovascular-kidney-liver-metabolic disease: global estimates, trends, and its attributable risk factors from 1990 to 2023

Background/Introduction The cardiovascular-kidney-liver-metabolic (CKLM) framework represents the multi-organ interplay of systemic metabolic disorders that drive the global burden of atherosclerotic cardiovascular disease (CVD). The CKLM epidemics constitute a ‘syndemic’ (or synergy of epidemics), underpinned by shared patho-mechanistic pathways and socioeconomic influences. Understanding the epidemiological trends across the CKLM syndemic is essential for developing integrated solutions that address its shared drivers and combined challenges. Purpose This study extends the literature by leveraging on epidemiological evidence from the Global Burden of Disease (GBD) 2023 study to map global epidemiological trends across the CKLM syndemic as well as their shared risk factors, stratified by age-group, sex, geographical region, and level of socioeconomic development. The study seeks to provide a contextualised roadmap to strategise targeted and shared interventions in addressing the trajectory of the CKLM syndemic now, and in the future. Methods The study used estimates from the GBD 2023 study to examine 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). Epidemiological trends were stratified by age, sex, region, and sociodemographic index (SDI). Results In 2023, the global CKLM burden contributed to 626.7 million DALYs, with an age-standardised DALY rate of 6,944.3 per 100,000 population. Atherosclerotic CVD was the largest contributor to the CKLM burden (3,924.2 [95%UI: 3,666.9-4,181.4]), followed by obesity (1,500.0 [95%UI: 730.4-2,206.5]), T2D (956.7 [95%UI: 794.4-1,142.4]), CKD (523.8 [95%UI: 468.0-590.1]), and MASLD (39.6 [95%UI: 31.2-49.9]). From 1990 to 2023, there was 24.4% reductions in CKLM-related age-standardised DALYs, primarily driven by improvements in atherosclerotic CVD (-41.5% decrease). This was counterbalanced by rapid increases in age-standardised DALYs attributed by T2D (37.5% increase), followed by obesity (23.3% increase), MASLD (1.8% increase) and CKD (0.6% increase). Disparities in CKLM burden exist across SDI (low to middle SDI bearing the highest burden), geography (North Africa and Middle-East bearing the highest burden), and age-sex categories (males bearing higher burden with an accelerated CKLM pattern in early life-course). Conclusion Improvements in the global atherosclerotic cardiovascular-kidney-liver-metabolic burden, driven by preventive gains in atherosclerotic CVD prevention, are offset by the rising burden of upstream CKLM drivers including obesity, T2D, CKD and MASLD. Preventive efforts need to address the CKLM “best-buys”, while addressing age-sex-location-socioeconomic disparities across the CKLM spectrum.