Reproductive Factors and Incidence of Heart Failure Hospitalization in the Women's Health Initiative

Abstract

Background: Reproductive factors reflective of endogenous sex hormone exposure might have an effect on cardiac remodeling and the development of heart failure (HF).

Objectives: This study examined the association between key reproductive factors and the incidence of HF.

Methods: Women from a cohort of the Women's Health Initiative were systematically evaluated for the incidence of HF hospitalization from study enrollment through 2014. Reproductive factors (number of live births, age at first pregnancy, and total reproductive duration [time from menarche to menopause]) were self-reported at study baseline in 1993 to 1998. We employed Cox proportional hazards regression analysis in age- and multivariable-adjusted models.

Results: Among 28,516 women, with an average age of 62.7 ± 7.1 years at baseline, 1,494 (5.2%) had an adjudicated incident HF hospitalization during an average follow-up of 13.1 years. After adjusting for covariates, total reproductive duration in years was inversely associated with incident HF: hazard ratios (HRs) of 0.99 per year (95% confidence interval [CI]: 0.98 to 0.99 per year) and 0.95 per 5 years (95% CI: 0.91 to 0.99 per 5 years). Conversely, early age at first pregnancy and nulliparity were significantly associated with incident HF in age-adjusted models, but not after multivariable adjustment. Notably, nulliparity was associated with incident HF with preserved ejection fraction in the fully adjusted model (HR: 2.75; 95% CI: 1.16 to 6.52).

Conclusions: In post-menopausal women, shorter total reproductive duration was associated with higher risk of incident HF, and nulliparity was associated with higher risk for incident HF with preserved ejection fraction. Whether exposure to endogenous sex hormones underlies this relationship should be investigated in future studies.

Keywords: cardiovascular disease; menarche; menopause; pregnancy; women.

Figure 1. Creation of the Study Sample: WHI

After excluding patients with cardiovascular disease (CVD) and missing reproductive data, the study included 28,516 participants from the University of North Carolina (UNC) heart failure (HF) cohort of the WHI (Women’s Health Initiative).

CENTRAL ILLUSTRATION. Reproductive Factors and Incidence of HF

We examined the association between key reproductive factors and incidence of heart failure (HF) in a cohort of the WHI (Women’s Health Initiative). Hazard ratios and 95% confidence intervals (CIs) were adjusted for age at screening, household income, education level, ethnicity, U.S. region, body mass index, hypertension, diabetes, hyperlipidemia, smoking status, breastfeeding, history of pregnancy Loss, prior hysterectomy, and usage of oral contraception or menopausal hormone therapy. In postmenopausaL women, shorter total reproductive duration was associated with a higher risk of incident HF, and nulliparity was associated with a higher risk for incident heart failure with preserved ejection fraction (HFpEF). *Per year. †Compared with women with 1 Live birth. ‡Age of first pregnancy Lasting at Least 6 months at <20 years of age compared with referent $ 30 years of age. HFrEF = heart failure with reduced ejection fraction.