Cardiovascular-kidney-metabolic (CKM) syndrome is a health disorder that links obesity, diabetes, chronic kidney disease, and heart disease.
These conditions connect and make each other worse over time.
Defined cardiovascular-kidney-metabolic (CKM) syndrome as a systemic disorder characterized by pathophysiological interactions among metabolic risk factors, chronic kidney disease (CKD), and the cardiovascular system, leading to multiorgan dysfunction and a high rate of adverse cardiovascular outcomes.
It encompasses both individuals at risk for CVD (due to metabolic risk factors, CKD, or both) and those with established CVD complicating those conditions, and is influenced by unfavorable social/environmental conditions for lifestyle and self-care.
Stages of CKM Syndrome
Staging framework (Stage 0–4) reflects typical pathophysiologic progression, most often originating from excess/dysfunctional adiposity.
Stage 0: No risk factors; optimal health. Stage 0 — No CKM risk factors: normal BMI and waist circumference, normoglycemia, normotension, normal lipids, no CKD or CVD.
Stage 1: Excess body fat or prediabetes. Stage 1 — Excess or dysfunctional adiposity: BMI ≥25 kg/m² (≥23 if Asian ancestry), or abdominal obesity (waist ≥88/102 cm in women/men; ≥80/90 cm if Asian ancestry), or fasting glucose 100–125 mg/dL or HbA1c 5.7–6.4%, without other metabolic risk factors or CKD.
Stage 2: High blood pressure, type 2 diabetes, high triglycerides, or chronic kidney disease. Metabolic risk factors, CKD, or both: hypertension (SBP ≥130 or DBP ≥80 mm Hg or on antihypertensives), hypertriglyceridemia ≥150 mg/dL, metabolic syndrome, T2D (FPG ≥126 mg/dL or HbA1c ≥6.5%), and/or moderate-to-high-risk CKD per KDIGO.
Stage 3: Early or hidden signs of heart or blood vessel disease. Subclinical CVD in CKM: subclinical coronary atherosclerosis (e.g., CAC ≥100) or pre-HF (elevated NT-proBNP ≥125 pg/mL, hs-cTnT ≥14 ng/L women/≥22 men, hs-cTnI ≥10 women/≥12 men, or echo abnormalities); or a risk equivalent—very high-risk CKD (G4–G5 or very high KDIGO risk) or predicted 10-year CVD risk ≥20% by PREVENT.
Stage 4: Diagnosed heart disease, stroke, or severe complications. Clinical CVD in CKM (CHD, HF, stroke, PAD, AF) Stage 4a without kidney failure; Stage 4b with kidney failure (eGFR <15 mL/min/1.73m² or chronic kidney replacement therapy).
Main Risks and Signs
Extra weight around the waist High blood sugar or cholesterol Shortness of breath or chest pain Swelling in the legs or feet Extreme tiredness
Staging is bidirectional—regression is possible with lifestyle change and weight loss.
Stage the syndrome in youths and adults to prevent progression, tailor therapy to absolute risk, and promote regression.
Quantify CVD risk with the PREVENT equations (10- and 30-year ASCVD, HF, total CVD).
A ≥20% 10-year risk is a Stage 3 criterion; ≥7.5% helps prioritize pharmacotherapy.
Routinely assess metabolic risk factors and kidney function (both eGFR and UACR), plus selective screening for pre-HF, MASLD, and OSA; assess and address social determinants of health.
Address overweight/obesity with BMI and waist circumference; emphasize lifestyle modification, with obesity pharmacotherapy and metabolic/bariatric surgery as needed.
Use cardioprotective antihyperglycemic GDMT in T2D with or at risk for CVD—SGLT2 inhibitors, GLP-1–based therapy, or both—guided by comorbidities (CKD, ASCVD, HF, obesity, MASLD).
Kidney protection: for CKD with T2D or albuminuria, RASi and SGLT2i are first-line; add a nonsteroidal MRA or GLP-1–based therapy if albuminuria persists.
Hypertension: goal <130/80 mm Hg; first-line agents are RASi, thiazide-type diuretics, and long-acting dihydropyridine CCBs, with RASi preferred inCKD with albuminuria. . CKM is not merely coexisting chronic diseases but a self-reinforcing pathological network, that most often originates from excess or dysfunctional (especially visceral) adipose tissue, which secretes proinflammatory and prooxidative mediators that promote insulin resistance, atherosclerosis, myocardial injury, glomerulosclerosis, and kidney fibrosis.
MASLD amplifies systemic inflammation and insulin resistance, and ectopic (epicardial, perirenal) fat contributes local injury.
Epidemiology. The burden is substantial—an analysis of U.S. adults found nearly 90% met criteria for at least Stage 1 CKM syndrome, reflecting the high prevalence of excess adiposity and metabolic risk.
CKM syndrome in younger adults with an average age of 23 nearly 80% signs have igns of arterial injury of plaque buildup within the carotid arteries.
The staging concept can be visualized as a progressive continuum from early metabolic dysfunction to overt multiorgan disease.