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

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.

Reproductive factors and risk of cardiovascular diseases and all-cause and cardiovascular mortality in American women: NHANES 2003-2018

“…Some studies have suggested that early menarche is associated with an increased risk of CVDs in women (15)(16)(17). However, a study from Korea determined that late menarche was associated with an increased risk of MI, but early age at menarche was not (13). Another study of 1,088,992 premenopausal women found that late menarche was associated with an increased risk of all-cause disease, while early menarche was not(18).…”

Age at menopause and risk of ischemic stroke: a systematic review and meta-analysis

“…Table 2 shows the summary estimates from the meta-analysis of the association between age at menopause and ischemic stroke. Of these 10 studies, 5 studies defined menopausal age before 45 years old as early menopause [16][17][18][19][20] , The other 5 studies defined menopausal age before 49, 47, 43, 42, and 40 years old as early menopause, respectively [21][22][23][24][25] (Table1). For the age at menopause and the incidence of ischemic stroke, Table2B,2C,2D demonstrate the risk of menopause and ischemic stroke for women whose age at menopause was before 45, 49 and 43 years, respectively.…”

The Relationship Between Myocardial Infarction and Estrogen Use: A Literature Review

“…Inherited genetic variants may also affect lipid metabolism and cholesterol levels, influencing plaque accumulation and atherosclerosis development, a major cause of MI. Epigenetic processes also mediate estrogen's effects, with studies showing that estrogen utilization and cognitive functions like memory enhancement are dependent on epigenetic mechanisms [27].…”