Adverse Pregnancy Outcomes and Incident Heart Failure in the Women's Health Initiative

Aleksander L. Hansen, Marc Meller Søndergaard, Mark A. Hlatky, Eric Vittinghof, Gregory Nah, Marcia L. Stefanick, Jo Ann E. Manson, Leslie V. Farland, Gretchen L. Wells, Morgana Mongraw-Chaffin, Erica P. Gunderson, Linda Van Horn, Robert A. Wild, Buyun Liu, Aladdin H. Shadyab, Matthew A. Allison, Simin Liu, Charles B. Eaton, Michael C. Honigberg, Nisha I. Parikh*


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Importance: Some prior evidence suggests that adverse pregnancy outcomes (APOs) may be associated with heart failure (HF). Identifying unique factors associated with the risk of HF and studying HF subtypes are important next steps. Objective: To investigate the association of APOs with incident HF overall and stratified by HF subtype (preserved vs reduced ejection fraction) among postmenopausal women in the Women's Health Initiative (WHI). Design, Setting, and Participants: In 2017, an APO history survey was administered in the WHI study, a large multiethnic cohort of postmenopausal women. The associations of 5 APOs (gestational diabetes, hypertensive disorders of pregnancy [HDP], low birth weight, high birth weight, and preterm delivery) with incident adjudicated HF were analyzed. In this cohort study, the association of each APO with HF was assessed using logistic regression models and with HF subtypes using multinomial regression, adjusting for age, sociodemographic characteristics, smoking, randomization status, reproductive history, and other APOs. Data analysis was performed from January 2020 to September 2021. Exposures: APOs (gestational diabetes, HDP, low birth weight, high birth weight, and preterm delivery). Main Outcomes and Measures: All confirmed cases of women hospitalized with HF and HF subtype were adjudicated by trained physicians using standardized methods. Results: Of 10292 women (median [IQR] age, 60 [55-64] years), 3185 (31.0%) reported 1 or more APO and 336 (3.3%) had a diagnosis of HF. Women with a history of any APO had a higher prevalence of hypertension, diabetes, coronary heart disease, or smoking. Of the APOs studied, only HDP was significantly associated with HF with a fully adjusted odds ratio (OR) of 1.75 (95% CI, 1.22-2.50), and with HF with preserved ejection fraction in fully adjusted models (OR, 2.06; 95% CI, 1.29-3.27). In mediation analyses, hypertension explained 24% (95% CI, 12%-73%), coronary heart disease 23% (95% CI, 11%-68%), and body mass index 20% (95% CI, 10%-64%) of the association between HDP and HF. Conclusions and Relevance: In this large cohort of postmenopausal women, HDP was independently associated with incident HF, particularly HF with preserved ejection fraction, and this association was mediated by subsequent hypertension, coronary heart disease, and obesity. These findings suggest that monitoring and modifying these factors early in women presenting with HDP may be associated with reduced long-term risk of HF..

Udgave nummer12
StatusUdgivet - 9 dec. 2021

Bibliografisk note

Funding Information:
Funding/Support: The Women’s Health Initiative program was funded by the NHLBI, NIH, and US Department of Health and Human Services through contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, and HHSN268201100004C. Mr Hansen was supported by a Danish American Research Exchange award from the Lundbeck Foundation, Fonden til Lægevidenskabens Fremme from the A. P. Moller Foundation, and travel grants from University of Southern Denmark and Odense University Hospital. Drs Parikh and Gunderson are supported by NIH grant R56HL148260. Dr Honigberg is supported by NHLBI grant T32HL094301-07.

Funding Information:
Author Contributions: Dr Parikh had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: Hansen, Manson, Van Horn, S. Liu, Parikh. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: Hansen, Wild, Parikh. Critical revision of the manuscript for important intellectual content: All authors. Statistical analysis: Hansen, Søndergaard, Vittinghoff, Nah, Stefanick, Mongraw-Chaffin, S. Liu, Parikh. Obtained funding: Eaton. Administrative, technical, or material support: Hansen, Manson, Farland, Van Horn, S. Liu, Parikh. Supervision: Søndergaard, Manson, Farland, Van Horn, Wild, Allison, Honigberg, Parikh. Conflict of Interest Disclosures: Dr Manson reported receiving grants from National Institutes of Health (NIH) during the conduct of the study. Dr Gunderson reported receiving grants from the NIH for primary data collection for the Division of Reasearch Women’s Health Initiative site for participants and data collection during the conduct of the study, the National Institute of Diabetes and Digestive and Digestive and Kidney Diseases (NIDDK R01 SWIFT Women Follow Up, NIDDK R01 SWIFT Study in Youth, and NIDDK R01 CARDIA Pregnancy RF and T2D), the National Heart, Lung, and Blood Institute (NHLBI R01 Pregnancy Blood Pressure and CVD and NHLBI R21 CARDIA Pregnancy SMM), the American Heart Association Project on Gestational Diabetes Mellitus and GrimAge, and Janssen Metabolomics for research on type 2 diabetes after gestational diabetes outside the submitted work; in addition, Dr Gunderson had a patent for metabolites and type 2 diabetes pending. No other disclosures were reported.

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© 2021 American Medical Association. All rights reserved.


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