Adiponectin is an adipocyte-derived hormone with anti-inflammatory and insulin-sensitizing properties that has been implicated in cardiovascular protection. However, prospective evidence regarding its sex-specific association with cardiovascular disease (CVD) remains limited. We investigated whether serum adiponectin independently predicts incident CVD according to sex in a population-based cohort.

We analyzed 3,540 participants (1,476 men and 2,064 women) without baseline CVD from the Korean Genome and Epidemiology Study (KoGES)-ARIRANG cohort. Serum adiponectin concentrations were categorized into sex-specific quartiles. Incident CVD, including myocardial infarction, angina, and stroke, was assessed over a median follow-up of 5.2 years. Multivariable Cox proportional hazards models adjusted for age, LDL cholesterol, smoking status, and high-sensitivity C-reactive protein were used. Restricted cubic spline analyses evaluated nonlinear associations.

During follow-up, 312 participants developed CVD. In the overall cohort, lower adiponectin concentrations were associated with an increased risk of CVD, although the association was attenuated after multivariable adjustment (lowest vs. highest quartile: hazard ratio [HR] 1.40, 95% confidence interval [CI] 0.93–2.12). In sex-stratified analyses, low adiponectin remained an independent predictor of incident CVD only in women (HR 1.85, 95% CI 1.08–3.20), whereas no significant association was observed in men. Lower adiponectin concentrations were also associated with greater waist circumference and higher triglyceride levels. Spline analyses demonstrated a nonlinear inverse association in women, with CVD risk increasing sharply at lower adiponectin concentrations.

Low serum adiponectin independently predicts incident CVD in women but not in men. These findings suggest that adiponectin may serve as a sex-specific biomarker for cardiovascular risk stratification beyond conventional cardiometabolic risk factors.