Cardiovascular-Kidney-Metabolic (CKM) Syndrome integrates metabolic risk factors, chronic kidney disease, and cardiovascular dysfunction, and is closely linked to future cardiovascular disease risk. This study published in the Metabolism evaluated sex-specific differences in prevalence, CKM components, and clinical outcomes among participants without established cardiovascular disease.

A total of 6,563 adults (3,095 men and 3,468 women; mean age 62 ± 10 years) from the Multi-Ethnic Study of Atherosclerosis were included. CKM stages were defined according to American Heart Association criteria. Sex-specific prevalence, distribution of CKM components, and incidence of heart failure (HF), coronary heart disease (CHD), stroke, and mortality were assessed. Incidence rates (IR) per 1,000 person-years and Fine-Gray sub-distribution hazard ratios (SHR) were estimated.

Compared with women, men had SHRs (95% CI) of 2.28 (1.84–2.82) for CHD, 1.66 (1.20–2.30) for HF, and 1.07 (0.80–1.43) for stroke. Within Stage 3, subclinical atherosclerotic cardiovascular disease, defined by coronary artery calcium score ≥100 Agatston units, predominated in men (70.5%), whereas subclinical HF characterized by elevated cardiac biomarkers was more frequent in women (70.1%). Over a median follow-up of 13.7 years (IQR 9.0–15.5), CHD incidence was higher in men (IR 20.9 vs. 8.9), followed by HF (7.2 vs. 4.5) and stroke (6.7 vs. 6.3).

Men demonstrated higher advanced CKM prevalence and greater CHD burden, while women more often exhibited a subclinical HF phenotype. These findings support sex-specific, stage-based CKM assessment as a framework for early risk stratification and tailored cardiovascular prevention.