Sex-specific differences in premature atherosclerotic cardiovascular disease: A meta-analysis

Background Premature atherosclerotic cardiovascular disease (pASCVD) is a major global health burden, with important sex-specific differences in cardiovascular risk factors. Purpose In this systematic review and meta-analysis, we evaluated sex-specific differences among patients with premature ASCVD compared with age-matched controls. Methods We searched electronic databases through December 2025 to identify studies comparing patients with pASCVD and age-matched healthy controls. Primary outcomes were differences in demographic, lifestyle, clinical, and biochemical risk factors between patients and controls, and sex-specific differences among patients. Secondary analyses assessed the magnitude of associations and pooled mean differences. Results Sixty-five studies (43,644 participants: 12,947 pASCVD patients and 30,697 controls; mean age 44.1±1.2 years) were included. Patients with pASCVD had significantly more adverse lipid and lipoprotein profiles than controls in both sexes (p < 0.01 for all). In sex-specific analyses among patients, men had lower levels of total cholesterol (TC: MD −0.24 mmol/L, 95% CI −0.48 to −0.01; p = 0.04), LDL-C (MD −0.20 mmol/L, 95% CI −0.37 to −0.02; p = 0.03), HDL-C (MD −0.22 mmol/L, 95% CI −0.30 to −0.15; p = 0.03), Lp(a) (MD −1.12 mg/dL, 95% CI −2.11 to −0.11; p = 0.02) and CRP (MD −0.99 mg/L, 95% CI −1.51 to −0.09; p = 0.03) compared with women. No significant sex differences were observed for triglycerides, ApoA, ApoB, or homocysteine (p > 0.05 for all) (Figure 1A). Men were more often current smokers (52% vs 42%; p = 0.001), former smokers (17% vs 12%; p = 0.044), alcohol consumers (61% vs 37%; p < 0.001), and had a higher prevalence of dyslipidaemia (54% vs 43%; p = 0.046) versus women. Women had higher rates of hypertension (46% vs 32%; p < 0.001), obesity (33% vs 22%; p = 0.012), premature family history of ASCVD (31% vs 23%; p = 0.011), and use of lipid-lowering therapy (45% vs 35%; p = 0.022). No sex differences were observed for diabetes, overall family history, or overweight status (Figure 1B). Conclusion Premature ASCVD is associated with an adverse cardiometabolic profile and marked sex-specific differences in risk factor distribution. These findings support the need for sex-tailored prevention strategies.