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. 2022 Apr 26;79(16):1594-1603.
doi: 10.1016/j.jacc.2022.02.020.

Infertility and Risk of Heart Failure in the Women's Health Initiative

Emily S Lau  1 , Dongyu Wang  2 , Mary Roberts  3 , Christy N Taylor  4 , Gayathree Murugappan  5 , Aladdin H Shadyab  6 , Peter F Schnatz  7 , Leslie V Farland  8 , Malissa J Wood  9 , Nandita S Scott  9 , Charles B Eaton  3 , Jennifer E Ho  10
Affiliations

Infertility and Risk of Heart Failure in the Women's Health Initiative

Emily S Lau et al. J Am Coll Cardiol. .

Abstract

Background: There is growing recognition that reproductive factors are associated with increased risk of future cardiovascular disease. Infertility has been less well studied, although emerging data support its association with increased risk of cardiovascular disease. Whether infertility is associated with future risk of heart failure (HF) is not known.

Objectives: This study sought to examine the development of HF and HF subtypes in women with and without history of infertility.

Methods: We followed postmenopausal women from the Women's Health Initiative prospectively for the development of HF. Infertility was self-reported at study baseline. Multivariable cause-specific Cox models were used to evaluate the association of infertility with incident overall HF and HF subtypes (heart failure with preserved ejection fraction [HFpEF]: left ventricular ejection fraction of ≥50% vs heart failure with reduced ejection fraction [HFrEF]: left ventricular ejection fraction of <50%]).

Results: Among 38,528 postmenopausal women (mean age: 63 ± 7 years), 5,399 (14%) participants reported a history of infertility. Over a median follow-up of 15 years, 2,373 developed incident HF, including 807 with HFrEF and 1,133 with HFpEF. Infertility was independently associated with future risk of overall HF (HR: 1.16; 95% CI: 1.04-1.30; P = 0.006). Notably, when examining HF subtypes, infertility was associated with future risk of HFpEF (HR: 1.27; 95% CI: 1.09-1.48; P = 0.002) but not HFrEF (HR: 0.97; 95% CI: 0.80-1.18).

Conclusions: Infertility was significantly associated with incident HF. This was driven by increased risk of HFpEF, but not HFrEF, and appeared independent of traditional cardiovascular risk factors and other infertility-related conditions. Future research should investigate mechanisms that underlie the link between infertility and HFpEF.

Keywords: heart failure; infertility; women.

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Conflict of interest statement

Funding Support and Author Disclosures The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts 75N92021D00001, 75N92021D00002, 75N92021D00003, 75N92021D00004, and 75N92021D00005. Dr Lau is supported by the American Heart Association (853922). Dr Ho is supported by the National Institutes of Health (R01-HL134893, R01-HL140224, and K24-HL153669). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

Figure 1.
Figure 1.. Incident Heart Failure Among Women With and Without Infertility.
The cumulative incidence plots reflect incident heart failure among women with history of infertility (red line) and without history of infertility (blue line).
Figure 2.
Figure 2.. Association of infertility with incident HF and HF subtypes.
Women with a history of infertility had increased hazards of HF and HFpEF. Age-adjusted and multivariable-adjusted Cox proportional hazards models begin follow-up at study enrollment. Multivariable-adjusted models were adjusted for age at screening, BMI, systolic blood pressure, hypertension treatment, DM, hyperlipidemia, smoking status (current and former), baseline CHD, and cohort (observational study or clinical trial). Abbreviations: CI = confidence interval, HF = heart failure, HFpEF = heart failure with preserved ejection fraction, HFrEF= heart failure with reduced ejection fraction, HR = hazard ratio
Central Illustration.
Central Illustration.. Infertility is associated with future HFpEF, but not HFrEF.
Women with a history of infertility had greater risk of incident heart failure, specifically heart failure with preserved ejection fraction. This association did not appear to be explained by traditional cardiovascular risk factors or infertility-related factors. Abbrevations: HF = heart failure, HFpEF = heart failure with preserved ejection fraction, HFrEF = heart failure with reduced ejection fraction, HR = hazard ratio
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