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Study Finds Infertility Associated With Future Risk of Heart Failure


While not routinely considered as part of the cardiovascular risk assessment, new study findings indicate a woman’s reproductive history may be a predictor of her heart disease risk.

There is a growing recognition that sex-specific and reproductive factors, including premature menopause and adverse pregnancy outcomes, increase risk of future cardiovascular disease.  However, infertility is one reproductive factor that has gone underrecognized with respect to heart health risk, in part because of the lack of rigorous data examining heart health risk in women with a history of the condition.  Although infertility affects ~1 in 5 women in the US, its link with heart failure has not been well-studied until recently.

In a study just published in the April 26 issue of Journal of the American College of Cardiology, researchers from Massachusetts General Hospital (MGH) found that women who had experienced infertility had a 16% increased risk of heart failure compared with women who did not have an infertility history.

More common in females

Heart failure is a major public health concern, affecting over 6 million individuals and accounting for over 1 million hospital admissions per year in the United States.  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 volume percentage of blood that is pumped from the left ventricle of the heart during each beat.  An ejection fraction less than 50% is commonly viewed as abnormal or reduced.  Notably, the prevalence of HFpEF, now the leading form of heart failure, is higher in women compared with men.

Infertility and future risk

The MGH team found an association between infertility and overall heart failure, specifically with HFpEF, which has been found to be far more common in women regardless of fertility history.  Partnering with the Women’s Health Initiative (WHI), the MGH investigators studied 38,528 postmenopausal women from the WHI and explored whether infertility was associated with development of heart failure.

Among the women studied, 14% of the participants reported a history of infertility.  Over a 15-year follow up period, the researchers noted that infertility was associated with 16% future risk of overall heart failure.  When they examined heart failure subtypes, they found that infertility was associated with a 27% increased future risk of HFpEF.

The researchers found that the increased risk was independent of traditional cardiovascular risk factors and other infertility-related conditions.  Further, the team did not find that cardiometabolic risk factors explained the link between infertility with heart failure in this study. They also explored other infertility-related conditions such as thyroid disease, irregular menses, and early menopause, to ascertain if these explained the association between infertility and heart failure but did not find evidence to support that hypothesis either.  Of note, the team observed that the link persisted regardless of whether an individual eventually conceived or had a live birth.

The infertility tip-off

The authors note that their work adds to the growing body of women’s heart failure research citing previous studies demonstrating a higher risk of heart failure among women with history of preeclampsia, particularly recurrent preeclampsia, as well as nulliparity and shorter total reproduction duration.

And while a woman’s reproductive history is unalterable, they emphasize that providers’ awareness of that history can impact future outcomes by serving as an early alert for intervention.  Since patients do not tend to develop heart failure until well in their 60s and beyond, and infertility is mostly experienced in the 20s, 30s, and 40s, providers’ cognizanceof a patient’s infertility should now raise clinical suspicion about HF and prompt more robust counseling regarding risk factors that are modifiable such as high blood pressure, high cholesterol, and smoking.

They conclude that since the association between infertility and heart failure did not appear to be explained by traditional cardiovascular risk factors, ischemic heart disease, or infertility-associated factors, future studies are needed to identify the mechanisms that underlie the association between infertility and heart failure.

The research was supported in part by the National Institutes of Health and American Heart Association.  The Women’s Health Initiative program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services.

Find the full paper, “Infertility and Risk of Heart Failure in the Women’s Health Initiative” and a companion editorial, “Infertility: A Fertile Ground for Heart Failure?” at https://www.jacc.org/doi/10.1016/j.jacc.2022.02.020

The contents of this feature are not provided or reviewed by NPWH.

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