From Risk Determinants to Clinical Action

ABSTRACT: The cardiovascular-kidney-metabolic (CKM) syndrome is a major and growing global health burden, with disproportionate impact among socioeconomically disadvantaged populations. It reflects the interconnectedness of cardiovascular disease, chronic kidney disease, and metabolic dysfunction, driven by excess adiposity (particularly visceral obesity and ectopic fat deposition), insulin resistance, inflammation, vascular dysfunction, and other metabolic perturbations. The American Heart Association (AHA) introduced the CKM syndrome framework, defining a five-stage (0-4) continuum that captures progressive risk of cardiovascular morbidity and mortality. AHA also proposed a CKM health framework that emphasizes multidisciplinary care of patients with CKM syndrome for early detection, monitoring, and prevention at the health systems and population health levels. This approach is aligned with the integrated cardio-kidney-metabolic care principles advocated by key professional societies such as the American Society of Nephrology (ASN), Kidney Disease Improving Global Outcomes (KDIGO), and the American Diabetes Association (ADA). This review synthesized current evidence on the development and progression of CKM syndrome, highlighting the important roles of biological mechanisms, shared risk factors, and social determinants of health (SDOH) in driving its complex, multidirectional pathophysiology. We summarized key components of the CKM health framework and discussed how combining lifestyle interventions with CKM-targeted, multi-disease-modifying pharmacotherapies often necessitates multidisciplinary approach to optimize CKM care. Finally, we outlined practical considerations and emerging strategies for co-adapting and integrating CKM care into routine clinical practice, drawing on implementation frameworks to enhance feasibility, adoption, and sustainability. These efforts may help inform ongoing multicenter initiatives to develop CKM clinical practice and public health guidelines and ultimately address underlying risk factors and SDOH to reduce cardiovascular, kidney, and metabolic morbidity and mortality.