Associations of reproductive factors with incidence of myocardial infarction and ischemic stroke in postmenopausal women: a cohort study

BMC Med. 2023 Feb 20;21(1):64. doi: 10.1186/s12916-023-02757-2.

Abstract

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.

Keywords: Age at menarche; Age at menopause; Cardiovascular disease; Postmenopausal women; Reproductive span.

MeSH terms

  • Age Factors
  • Cohort Studies
  • Female
  • Humans
  • Incidence
  • Ischemic Stroke*
  • Menarche
  • Menopause
  • Myocardial Infarction* / epidemiology
  • Postmenopause
  • Retrospective Studies
  • Risk Factors