Preventing progression and promoting regression of cardiovascular-kidney-metabolic (CKM) syndrome requires early staging, comprehensive risk assessment, management of risk factors, and use of evidence-based therapies across the life course. CKM syndrome staging is recommended for youths and adults to guide treatment and reduce cardiovascular and kidney complications. Individuals with CKM stages 0–3 should have their risk assessed using the PREVENT equations to estimate 10- and 30-year risks of atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), and total cardiovascular disease (CVD), with the results informing CKM staging and treatment prioritization. Routine evaluation of metabolic risk factors, kidney function, pre-HF, metabolic dysfunction–associated steatotic liver disease, obstructive sleep apnea, and social determinants of health is recommended. Care should be coordinated through interdisciplinary teams with a designated point person to facilitate implementation of guideline-directed medical therapy. Overweight and obesity should be assessed using both body mass index (BMI) and waist circumference and managed through lifestyle modification, with obesity pharmacotherapies and metabolic or bariatric surgery used when needed. In patients with type 2 diabetes (T2D) and CVD or increased cardiovascular risk, cardioprotective antihyperglycemic therapies, including sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 (GLP-1)–based therapies, or both, are recommended. For chronic kidney disease (CKD), estimated glomerular filtration rate and urine albumin-to-creatinine ratio should guide treatment, with renin-angiotensin system inhibitors (RASi) and SGLT2i as first-line therapy in patients with CKD and T2D or albuminuria; if albuminuria persists, nonsteroidal mineralocorticoid receptor antagonists (MRA) or GLP-1–based therapies should be added. In patients with established ASCVD, management should emphasize obesity treatment, cardioprotective antihyperglycemic therapies, and kidney-protective agents. In HF, CKM factors should be integrated into treatment, with RAS inhibitors (ARNI, ACE inhibitors, or ARBs) and SGLT2i emphasized in HFrEF, and SGLT2i, GLP-1–based therapies, and selected nonsteroidal MRAs considered in HFmrEF/HFpEF according to comorbidities. Source: https://www.jacc.org/
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