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

Julie J Lee, Galen Cook-Wiens, B Delia Johnson, Glenn D Braunstein, Sarah L Berga, Frank Z Stanczyk, Carl J Pepine, C Noel Bairey Merz, Chrisandra L Shufelt, Julie J Lee, Galen Cook-Wiens, B Delia Johnson, Glenn D Braunstein, Sarah L Berga, Frank Z Stanczyk, Carl J Pepine, C Noel Bairey Merz, Chrisandra L Shufelt

Abstract

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/m2, 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.

Keywords: cardiovascular disease outcomes; estrogen; menarche; risk factors; women.

Figures

Figure 1
Figure 1
Adjusted relative hazard (with TET) and 95% CI of major adverse cardiac events (MACE) by age at menarche. TET indicates total estrogen time.
Figure 2
Figure 2
Adjusted relative hazard (with TET) and 95% CI of mortality by age at menarche. TET indicates total estrogen time.

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