Associations of reproductive factors with incidence of myocardial infarction and ischemic stroke in postmenopausal women: a cohort study
Authors and Affiliations
Authors and Affiliations
Su‑Min Jeong1,2,3†, Jung Eun Yoo4†, Keun Hye Jeon5, Kyungdo Han6, Heesun Lee7, Dong‑Yun Lee8 and Dong Wook Shin9,10*
1Department of Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
2Department of Family Medicine, Seoul National University Health Service Center, Seoul, Republic of Korea.
3Department of Family Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
4Department of Family Medicine, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul, Republic of Korea.
5Department of Family Medicine, CHA Gumi Medical Center, CHA University, Gumi, Republic of Korea.
6Department of Statistics and Actuarial Science, Soongsil University, Seoul, Republic of Korea.
7Department of Cardiology, Healthcare System Gangnam Center, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
8Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
9Department of Family Medicine/Supportive Care Center, Samsung Medical Center, Seoul, Republic of Korea.
10Department of Clinical Research Design & Evaluation, Samsung Advanced Institute for Health Science and Technology (SAIHST), Sungkyunkwan University, 81 Irwon‑Ro, Gangnam‑Gu, Seoul 06351, Republic of Korea.
†Su-Min Jeong and Jung Eun Yoo are co-frst authors.
*Correspondence: Dong Wook Shin
Background: To assess the association between the reproductive factors of age at menarche, age at menopause, and reproductive span and the incidence of myocardial infarction (MI) and ischemic stroke (IS).
Methods: We used a population-based retrospective cohort study from the National Health Insurance Service database of Korea including a total of 1,224,547 postmenopausal women. Associations between age at menarche (≤ 12, 13-14 [reference], 15, 16, and ≥ 17 years), age at menopause (< 40, 40-45, 46-50, 51-54 [reference], and ≥ 55 years), and reproductive span (< 30, 30-33, 34-36, 37-40 [reference], and ≥ 41 years) and the incidence of MI and IS were assessed by Cox proportional hazard models with adjustment for traditional cardiovascular risk factors and various reproductive factors.
Results: During a median follow-up of 8.4 years, 25,181 MI and 38,996 IS cases were identified. Late menarche (≥ 16 years), early menopause (≤ 50 years), and short reproductive span (≤ 36 years) were linearly associated with a 6%, 12-40%, and 12-32% higher risk of MI, respectively. Meanwhile, a U-shaped association between age at menarche and risk of IS was found, with a 16% higher risk in early menarche (≤ 12 years) and a 7-9% higher risk in late menarche (≥ 16 years). Short reproductive span was linearly associated with an increased risk of MI, whereas both shorter and longer reproductive spans were associated with an increased risk of IS.
Conclusions: This study demonstrated different patterns of association between age at menarche and incidence of MI and IS: a linear association for MI versus a U-shaped association for IS. Female reproductive factors in addition to traditional cardiovascular risk factors should be considered when assessing overall cardiovascular risk in postmenopausal women.