BACKGROUND AND PURPOSE:

• Zhu et al. (The Lancet, 2019) sought to determine the relationship between onset of menopause and cardiovascular (CVD) risk

METHODS:

• Pooled analysis of individual-level data from observational studies
  • Data derived from the International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events (InterLACE), a consortium of pooled individual-level data on reproductive health and chronic diseases
  • 15 studies were used across 5 countries/regions (Australia, Scandinavia, the USA, Japan, and the UK) from 1946 to 2013
• Participants
  • Women who reported their menopause status, age at natural menopause (if postmenopausal), and CVD status (including coronary heart disease and stroke)
  • Exclusion: History of hysterectomy or oophorectomy
• Groups
  • Premenopausal or perimenopausal
  • <40 years (premature menopause)
  • 40–44 years (early menopause)
  • 45–49 years (relatively early)
  • 50–51 years (reference category)
  • 52–54 years (relatively late)
  • ≥55 years or older (late menopause)
• Definitions
  • CVD: Composite outcome of incident coronary heart disease (including heart attack and angina)
  • Stroke: Ischemic or stroke
• Data analysis
  • Cox proportional hazards models to estimate multivariate hazard ratio (HR) and 95% CI
  • Adjusted for confounders, including smoking status, menopausal hormone therapy status, BMI, and education levels
• Primary outcome
  • Occurrence of first non-fatal cardiovascular disease or stroke

RESULTS:

• 301,438 women were included
  • First non-fatal CVD event after menopause:4.3%
    • Coronary heart disease: 3.1%
    • Stroke: 1.4%
• Compared to reference category, risk of CVD was
  • Higher in women who had premature menopause (p<0.0001)
    • <40 years: HR 1.55 (95% CI, 1.38 to 1.73)
  • Higher in women who had early menopause (p<0.0001)
    • 40–44 years: HR 1.30 (95% CI, 1.22 to 1.39)
  • Higher in women who had relatively early menopause (p<0.0001)
    • 45–49 years HR 1.12 (95% CI, 1.07 to 118)
  • Reduced in women with late menopause
    • >51 years: HR 0.88 (95% CI, 0.83 to 0.93; p<0·0001)
• Smoking did not alter the above associations
• The associations were strongest for CVD events before age 60 for women with
  • Premature menopause: HR 1.88 (95% CI, 1.62 to 2.20; p<0.0001)
  • Early menopause: HR 1.40 (95% CI, 1.27 to 1.54; p<0.0001)
  • However, the associations were attenuated at age 60–69 years and no longer present for events ≥70 years
• Women with early or premature onset who took HT for at least 10 years had lower risk for CVD compared to no HT or less than 10 years
  • In addition, menopausal HT initiation 1 year after menopause resulted in lower CVD risk than when HT was started more than 1 year after menopause

CONCLUSION:

• Premature and early menopause are associated with an increased risk of CVD prior to 70 years when compared to the reference range (50-51 years)
• Clinical implications of this study include
  • Women with early menopause may benefit from closer surveillance and active management of CVD risk factors  
  • Consideration of early menopause as a CVD risk factor
  • Encourage prevention strategies such as smoking cessation and maintaining normal BMI to reduce risk for early menopause

Learn More – Primary Sources:

Age at natural menopause and risk of incident cardiovascular disease: a pooled analysis of individual patient data

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