Early menopause as a female-specific prognostic marker after acute coronary syndrome in women aged 60 years or younger: a real-world multicenter registry analysis

Objective: Early menopause is an established female-specific risk enhancer for incident cardiovascular disease, but its prognostic value after acute coronary syndrome (ACS) remains uncertain. We evaluated whether menopause before age 45 years was associated with long-term ischemic/cardiovascular outcomes after ACS in midlife women. Methods: We analyzed a multicenter registry of women hospitalized with ACS from February 1, 2020 through February 28, 2025. The primary cohort included women whose menopause preceded or coincided with the index event. Menopausal age was obtained from structured registry/clinical history fields. The primary outcome was a prespecified ischemic/cardiovascular major adverse cardiovascular event. Results: Among 1,039 records, 857 had valid menopausal age data and 728 met temporal criteria. Menopause before age 45 years was present in 124 women; median follow-up was 3.52 years. Crude post-index event rates were higher with early versus later menopause for the primary outcome (21.1% vs. 13.3%), death (8.9% vs. 4.6%), and the composite outcome (25.2% vs. 15.3%). In the primary clinical Cox model, early menopause was associated with the primary outcome (hazard ratio [HR], 1.78; 95% CI, 1.11-2.85), death (HR, 2.57; 95% CI, 1.18-5.57), and the composite outcome (HR, 1.87; 95% CI, 1.21-2.89). Associations attenuated in extended exploratory models including previous vascular disease, surgical menopause, and hormone therapy. Conclusions: Menopause before age 45 years identified a higher risk post ACS phenotype. Findings extend incident risk evidence into secondary prevention and support routine recording of menopausal age; causality cannot be inferred.