History of Infertility Linked to Increased Risk of Heart Failure in Women

Emily Lau, MD, MPH

A history of infertility could increase a woman’s risk of developing heart failure by 16%, according to a new analysis of more than 35,000 postmenopausal women.

Using data from the Women’s Health Initiative, a team from Massachusetts General Hospital assessed risk of heart failure in a cohort of 38,528 postmenopausal women based on history of infertility and found a history of infertility was independently associated with a 16% increase in risk of future heart failure overall and a 27% greater risk of heart failure with preserved ejection fraction (HFpEF).

“We as scientists and doctors are beginning to recognize how important a woman's reproductive history is for their future risk of heart disease. Infertility is one of many cardiovascular risk factors, such as hypertension and high blood pressure, but reproductive history is not routinely considered as part of the cardiovascular risk assessment,” said lead investigator Emily Lau, MD, MPH, cardiologist and director of the Menopause, Hormones and Cardiovascular Clinic at Massachusetts General Hospital, in a statement. “We cannot change a woman’s history of infertility, but if we know a woman has had a history of infertility, we can be more aggressive about counseling her about other modifiable risk factors including high blood pressure, high cholesterol, smoking, and beyond.”

With support from the National Institutes of Health and the American Heart Association, the current study was conducted by Lau and a team of colleagues at Massachusetts General Hospital with an interest in furthering the knowledge base surrounding risk factors for heart failure among aging women. To do so, investigators designed their study as an analysis of data from the Women’s Health Initiative.

From the prospective study, investigators obtained data related to a cohort of 38,528 postmenopausal women for inclusion in their analyses. This cohort had a mean age of 63±7 years at baseline, 4399 (14%) reported a history of infertility, and, over a median follow-up of 15 years, 2373 developed incident heart failure, including 807 with heart failure with reduced ejection fraction (HFrEF) and 1133 with HFpEF.

For the purpose of analysis, investigators used multivariable cause-specific Cox models to assess associations of infertility with incident overall heart failures and heart failure subtypes. Investigators defined HFrEF as a left ventricular ejection fraction (LVEF) less than 50% and HFpEF as an LVEF of 50% or greater.

In adjusted analysis, results indicated infertility was independently associated with future risk of overall heart failure (HR, 1.16 [95% CI, 1.04-1.30]; P=.006). When assessing risk according to heart failure subtypes, infertility was associated with an increased risk of future HFpEF (HR, 1.27 [95% CI, 1.09-1.48]; P=.002), but this increase in risk was not observed for HFrEF (HR, 0.97 [95% CI, 0.80-1.18]).

Investigators pointed out additional analyses were performed to assess if the apparent increase in risk would be mediated by other infertility-related risk factors, such as irregular menses, thyroid disease, and waist circumference, and these analyses indicated these risk factors were associated with infertility, but not associated with incident heart failure risk.

In an editorial comment, Ersilia M. DeFilippis, MD, of Brigham and Women’s Hospital, commended both the study’s investigators for their efforts in furthering research and the participants of the Women’s Health Initiative for their contributions to science.

“One of the best ways to honor these research participants is to improve our history taking, early evaluation, and risk assessment of young women of reproductive age, both in clinical practice and as part of clinical trials. This should include an assessment of traditional cardiovascular risk factors but also inquire about age of menarche, difficulty conceiving, number of pregnancies and any adverse pregnancy outcomes, breastfeeding, and timing of menopause,” DeFilippis wrote.

This study, “Infertility and Risk of Heart Failure in the Women’s Health Initiative,” was published in the Journal of the American College of Cardiology.