Reproductive Factors and Heart Failure

Study Questions:

What is the association between reproductive factors and heart failure (HF) in women?


The study cohort was comprised of 44,174 subjects from the Women’s Health Initiative for whom HF outcomes were centrally adjudicated from enrollment beginning in 1993 through September 2014. The investigators evaluated the incidence of HF hospitalization in this cohort. They compared HF hospitalization to self-reported reproductive factors including number of live births, age at first pregnancy lasting at least 6 months, and total reproductive duration (time to menarche to menopause). Selected covariates included age at screening, household income, education level, ethnicity, U.S. region, body mass index (BMI), hypertension (defined by self-report, systolic blood pressure >140 mm Hg or diastolic blood pressure >90 mm Hg at screening, or use of antihypertensive medication), diabetes (defined by fasting glucose >126 mg/dl or use of diabetes medication), hyperlipidemia requiring the use of medication, smoking status, history of breastfeeding for ≥1 month, history of pregnancy loss, prior hysterectomy, and usage of oral contraception or menopausal hormone therapy. The primary outcome for this analysis was the time to development of a first hospitalization for definite or probable acute decompensated HF or newly diagnosed stable HF. They used Cox proportional hazards regression analysis in age- and multivariable-adjusted models.


The mean age of the study cohort (n = 28,516) was 62.7 (±7.1) years at baseline. The study investigators reported that 5.2% (n = 1,494) had an incident HF hospitalization with an average follow-up period of 13.1 years. Shorter total reproductive duration was associated with increased risk of HF, with an age-adjusted hazard ratio (HR) of 0.98 per year (95% confidence interval [CI], 0.97-0.98; p < 0.0001) and a multivariable-adjusted HR of 0.99 (95% CI, 0.98-0.99; p = 0.02). This equates to a 5-year adjusted HR of 0.95 (95% CI, 0.91-0.99). Whereas in age-adjusted models but not after multivariable adjustment, early age at first pregnancy (<20 years old) and nulliparity were significantly associated with incident HF (HR, 1.42; 95% CI, 1.16-1.75 and HR, 1.80; 95% CI, 1.07-3.03, respectively), particularly nulliparity was associated with incident HF with preserved ejection fraction (HFpEF) in both age-adjusted (HR, 2.57; 95% CI, 1.22-5.44) and the fully adjusted model (HR, 2.75; 95% CI, 1.16-6.52). Early age at first pregnancy and shorter total reproductive duration were associated with increased risk of HFpEF in age-adjusted, but not multivariable-adjusted models.


The study authors concluded that in postmenopausal women, shorter total reproductive duration was associated with higher risk of incident HF, and nulliparity was associated with higher risk for incident HFpEF.


Hormonal factors have been associated with peripartum cardiomyopathy, increased risk of coronary heart disease, and stroke. The important findings of this study that such factors may impact HF in postmenopausal women, certainly merit further investigation.

Clinical Topics: Dyslipidemia, Geriatric Cardiology, Heart Failure and Cardiomyopathies, Prevention, Atherosclerotic Disease (CAD/PAD), Acute Heart Failure, Hypertension, Smoking

Keywords: Antihypertensive Agents, Blood Pressure, Body Mass Index, Cardiomyopathies, Coronary Artery Disease, Diabetes Mellitus, Geriatrics, Glucose, Heart Failure, Hyperlipidemias, Hypertension, Hysterectomy, Menarche, Menopause, Parity, Peripartum Period, Postmenopause, Pregnancy, Smoking, Stroke, Women's Health

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