Summary

The growing epidemics of metabolic-dysfunction-associated steatotic liver disease, type 2 diabetes mellitus, obesity and cardiovascular disease are inextricably linked. Cardiovascular–liver–metabolic (CLM) diseases coexist and interact to constitute a synergy of epidemics (a syndemic), with shared mechanisms and socioeconomic influences. The goal of this Review is to construct this complex public-health issue into a unified framework, using epidemiological data to illustrate the current burden of disease and the trends in the CLM syndemic and to make projections for the future. We also discuss the challenges of promoting CLM health and the need for shared solutions. The proposed micro–meso–macro framework integrates strategies to improve risk prediction and precision prevention and to disentangle the competing risks within the CLM construct (micro), while keeping communities at the heart of CLM health promotion by ensuring access to healthy foods, healthy environments and metabolic interventions (meso). In addition, we propose interventions to eliminate inequities in the social and commercial determinants of health, from communities to healthcare systems (macro). Thus, multisystem interventions could address the trajectories of the CLM disease epidemics simultaneously.