Age at Menarche and Risk of Cardiovascular Disease Outcomes: Findings From the National Heart Lung and Blood Institute‐Sponsored Women's Ischemia Syndrome Evaluation

BACKGROUND: Previous studies have reported an association between the timing of menarche and cardiovascular disease (CVD). However, emerging studies have not examined the timing of menarche in relation to role of estrogen over a lifetime and major adverse cardiac events (MACE). METHODS AND RESULTS: A total of 648 women without surgical menopause undergoing coronary angiography for suspected ischemia in the WISE (Women's Ischemia Syndrome Evaluation) study were evaluated at baseline and followed for 6 years (median) to assess major adverse CVD outcomes. MACE was defined as the first occurrence of all‐cause death, nonfatal myocardial infarction, nonfatal stroke, or heart failure hospitalization. Age at menarche was self‐reported and categorized (≤10, 11, 12, 13, 14, ≥15 years) with age 12 as reference. Total estrogen time and supra–total estrogen time were calculated. Cox regression analysis was performed adjusting for CVD risk factors. Baseline age was 57.9 ± 12 years (mean ± SD), body mass index was 29.5 ± 6.5 kg/m(2), total estrogen time was 32.2 ± 8.9 years, and supra–total estrogen time was 41.4 ± 8.8 years. MACE occurred in 172 (27%), and its adjusted regression model was J‐shaped. Compared with women with menarche at age 12 years, the adjusted MACE hazard ratio for menarche at ≤10 years was 4.53 (95% CI 2.13‐9.63); and at ≥15 years risk for MACE was 2.58 (95% CI, 1.28‐5.21). CONCLUSIONS: History of early or late menarche was associated with a higher risk for adverse CVD outcomes. These findings highlight age at menarche as a potential screening tool for women at risk of adverse CVD events. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000554.