Infertility Linked to Increased Heart Failure Risk, Especially HFpEF

Ashley Lyles

April 21, 2022

Infertility is linked to a higher risk for incident heart failure, especially heart failure with preserved ejection fraction (HFpEF), a prospective cohort study suggests.

The data show that women with infertility were at greater risk of having heart failure in the future, which was mostly because of an increased risk for HFpEF rather than for heart failure with reduced ejection fraction (HFrEF). Coronary disease, conventional cardiovascular risk factors, and other infertility-linked disorders do not explain these findings, report Emily S. Lau, MD, MPH, Massachusetts General Hospital, Boston, and colleagues.

The findings were published in the April 26 issue of the Journal of the American College of Cardiology.

Discussion of what happened when patients were trying to get pregnant, whether they had adverse pregnancy outcomes or a history of infertility, and their experience with menopause are all important, noted Lau.

"All of these reproductive factors are incredibly important windows into a woman's future cardiovascular risk, and yet they are not routinely asked at primary care office visits or even cardiology office visits, but it is something we as physicians should be starting to ask our female patients," she told theheart.org | Medscape Cardiology in an interview.

Previous research does not offer a robust dataset on the relation between cardiovascular disease and infertility, especially heart failure," notes Ersilia M. DeFilippis, MD, Columbia University Irving Medical Center, New York City, in an accompanying editorial. An examination involving the Swedish Medical Birth registry indicated that women with a history of infertility who eventually became pregnant were at elevated risk for cardiovascular disease, but it did not look specifically at the risk for heart failure.

The Women's Health Initiative (WHI) has been useful in helping the medical community assess reproductive health and its relation with cancer, osteoporosis, and cardiovascular risk, she writes. To honor the research participants, efforts should be made to engage in early assessment, to enhance history taking, and to do risk evaluation of young women of reproductive age in clinical trials and in clinical practice, she writes. 

"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," the editorial notes.

"This risk assessment should be an iterative process as new information about a woman's reproductive health becomes available. This longitudinal knowledge can empower patients and physicians to optimize cardiovascular health for women throughout their lifespan," DeFilippis concludes.

For this report, Lau and colleagues analyzed 38,528 postmenopausal women, 14% of whom indicated they had a history of infertility. Mean age was 63 years.

Using WHI data, the study team prospectively assessed postmenopausal women to determine if they developed heart failure. Using multivariable cause-oriented Cox models, the investigators assessed the relation between infertility and heart failure subtypes, which included HFrEF, HFpEF, as well as overall heart failure.

Over a median follow-up of 15 years, 2373 developed incident HF, including 1133 with HFpEF and 807 with HFrEF.

Infertility was independently linked to risk of overall heart failure in the future (hazard ratio [HR], 1.16; = .006).

Additional data on heart failure subtypes showed infertility was not linked to HFrEF (HR, 0.97; 95% CI, 0.80 - 1.18), but it was associated with future risk for HFpEF (HR, 1.27; P = .002).

The study is observational in nature, which limits the researchers' ability to assess causation, participants self-reported their infertility status, which may have been subject to classification errors, postmenopausal women were enrolled in the WHI between 1993 and 1998, prior to the use of modern fertility therapies like in vitro fertilization, and lack of information on the period of infertility prior to pregnancy were limitations of the study, the authors note.

Other limitations include the fact that the research did not specifically look at microvascular disease, even though coronary heart disease did not account for the relation between heart failure and infertility, and the fact that baseline covariates — such as traditional cardiovascular risk factors, like waist circumference, blood pressure, and body mass index — were assessed at enrollment.

"Our findings highlight the need for rigorous studies investigating the mechanisms by which infertility may lead to future HFpEF and overall CV risk," the researchers conclude.

The WHI program is supported by the US Department of Health and Human Services and the National Heart, Lung, and Blood Institute, National Institutes of Health. Lau received support from the American Heart Association. DeFilippis reports no relevant financial relationships.

J Am Coll Cardiol. 2022;79:1594-1603, 1604-1605. Full text, Editorial

Ashley Lyles is an award-winning medical journalist. She is a graduate of New York University's Science, Health, and Environmental Reporting Program. Previously, she studied professional writing at Michigan State University, where she also took premedical classes. Her work has taken her to Honduras, Cambodia, France, and Ghana and has appeared in outlets like The New York Times Daily 360, PBS NewsHour, The Huffington Post, Undark, The Root, Psychology Today, Insider, and Tonic (Health by Vice), among other publications.

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