Infertility and the risk of cardiovascular disease: consider them in the context of all risk factors

Pr Geneviève Plu-Bureau, head of the medical gynecology unit at Port Royal Hospital, and gynecologist-endocrinologist Brigitte Raccah-Tebeka, Ambassadors of Agir pour le Cœur des Femmes, have highlighted the results of an American study published in 2023 on the cardiovascular risk associated with infertility, a situation still little known to the general public and healthcare professionals. This study once again underlines the close link between women's hormonal lives and their cardiovascular health, justifying close cooperation between GPs, gynecologists and cardiovascular physicians as part of coordinated treatment paths.

Cardiovascular disease has different risk factors for men and women. An increasing number of scientific studies are specifically analyzing the influence of reproductive factors and women's obstetrical history. While the latter (hypertensive disorders, preeclampsia, repeated miscarriages, etc.) have been the subject of several recent studies, few have analyzed the association between overall infertility, defined internationally as more than 12 months of unsuccessful attempts to conceive, and cardiovascular risk.

This very recent publication therefore aims to analyze this association, based on women participating in the Nurses' Health Study II (a large cohort study of American nurses) who either reported infertility (including those who succeeded in conceiving after this 12-month period) or who had had a child without infertility. During the follow-up of these women (from 1989 to 2017), various cardiovascular diseases were reported (coronary heart disease diagnosed by a physician (myocardial infarction n=782; coronary artery bypass graft, angioplasty, stent n=984) and strokes (CVA n=762 including 210 ischemic strokes). Among 103,729 women, 27.6% reported previous infertility. Compared with pregnant women who had not reported infertility, women with a history of infertility had a discretely but significantly increased risk of coronary heart disease (HR, 1.13 [95% CI, 1.01-1.26]), but no increased risk of stroke (HR, 0.91 [95% CI, 0.77-1.07]).

Furthermore, the younger the period of infertility, the greater the risk of coronary heart disease: for infertility first reported at ≤25 years, HR 1.26 [95% CI, 1.09-1.46]; HR at 26-30 years, 1.08 [95% CI, 0.93-1.25]; HR at > 30 years, 0.91 [95% CI, 0.70-1.19]).

Among women who had investigated an etiology for their infertility, the distribution was as follows: ovulatory disorders (39.1%) including the diagnosis of polycystic ovary syndrome, spousal/male factor infertility (25.7%), other cause (21.8%), endometriosis (21.5%) or no cause found (30.5%). Only ovulatory disorders or endometriosis were associated with the risk of coronary heart disease; HR, 1.28 [95% CI, 1.05-1.55]) and (HR, 1.42 [95% CI, 1.09- 1.85] respectively.

In conclusion, infertile women may be exposed to a discrete increased risk of coronary heart disease. This risk varied according to age at first diagnosis of infertility and appeared to be limited to infertility related to ovulation disorders and endometriosis.

What are the clinical implications? This publication reinforces the importance of paying attention to women's specific risk factors when assessing the risk of coronary heart disease.

More information:

Farland LV et al. Infertility and Risk of Cardiovascular Disease: A Prospective Cohort Study. J Am Heart Assoc. 2023 Feb 27:e027755.

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