“We’re beginning to recognize that a woman’s reproductive history says a lot about her future risk for heart disease,” says first author Emily Lau, MD, MPH, cardiologist and director of the Menopause, Hormones, and Clinic. of Cardiology at the MGH. “Whether a woman has difficulty getting pregnant, what happens during her pregnancies, when she goes through menopause, all of these influence her risk of heart disease later in life.”

Infertility affects approximately 1 in 5 American women and includes a range of difficulties in conceiving, but its link to heart failure has not been well studied until recently. In partnership with the Women’s Health Initiative (WHI), which was conceived in the early 1990s and interrogated a woman’s reproductive history, Lau and her colleagues studied postmenopausal women in the WHI and examined whether the infertility was associated with the development of heart failure.

There are two types of heart failure: heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). Ejection fraction is a measurement related to the percentage of blood volume that is pumped from the left ventricle of the heart during each beat. An ejection fraction below 50% is generally considered abnormal or reduced.

The team found an association between infertility and congestive heart failure, particularly with HFpEF, a form of heart failure that is much more common in women, regardless of their fertility history. Of the 38,528 postmenopausal women studied, 14% of participants reported a history of infertility. Over a 15-year follow-up period, researchers noted that infertility was associated with a 16% future risk of congestive heart failure. When they looked at heart failure subtypes, they found that infertility was associated with a 27% increased future risk of HFpEF.

Over the past decade, HFpEF (where the heart muscle does not relax well) as opposed to HFrEF (where the left ventricle does not pump well), has become the dominant form of heart failure in both men and women. But it remains more common in women. “It’s a difficult condition because we still don’t fully understand how HFpEF develops and we don’t have very good therapies to treat HFpEF,” says Lau.

“I think our findings are particularly remarkable because heart failure with preserved ejection fraction is more common in women,” Lau says. “We don’t understand why we see more HFpEF in women. Looking back into a woman’s early reproductive life can give us clues as to why.” It should be noted that the team observed that the link persisted whether an individual eventually conceived or had a live birth.

The increased risk was independent of traditional cardiovascular risk factors and other infertility-related conditions. “Previous studies have suggested that infertile women have more cardiometabolic risk factors,” says Lau, but the team did not find that cardiometabolic risk factors explained the link between infertility and heart failure in this study. They also looked to see if other infertility-related conditions like thyroid disease, irregular periods, and early menopause accounted for the association between infertility and heart failure, but also did not provide evidence to support this hypothesis.

“So this really begs the question: what are the mechanisms behind the association between infertility and heart failure,” Lau says. Are these shared risk factors or is infertility on the causal pathway? She mentions that vascular and endothelial dysfunctions may be involved and plans to eventually clarify the mechanism underlying the link between infertility and heart failure. In the future, Lau hopes to conduct a prospective study on women with a history of infertility involving exercise parameters, vascular measurements, etc., to solve the mystery.

“As scientists and physicians, we are beginning to recognize the importance of a woman’s reproductive history to her 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 cardiovascular risk assessment,” says Lau. Since people don’t tend to develop heart failure until their 60s and into Beyond that, and infertility mostly occurs in their 20s, 30s and 40s, many doctors don’t think about the connection.” We can’t change a woman’s history of infertility, but if we know that a woman has had a history of infertility, we may be more aggressive in counseling her about other modifiable risk factors including high blood pressure, high cholesterol mie, smoking and beyond.”

This research was funded in part by the National Institutes of Health and the American Heart Association.