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



Take Home Points:

  • Adverse pregnancy outcomes (APO) complicate up to 30% of pregnancies. Prior studies suggest that preeclampsia, hypertensive disorders of pregnancy and gestational diabetes may be associated with an increased risk of developing heart failure (HF), yet the potential impact of multiple APOs on heart failure occurrence and whether there is difference on the occurrence on heart failure with reduced ejection fraction (HFrEF) versus on heart failure with preserved ejection fraction (HFpEF) are unknown.
  • The aim of the study was to assess individual and joint associations between APOs in pregnancies lasting >6 months and HF using the Women’s Health Initiative (WHI) database. The WHI initiative is a longitudinal study of ethnically diverse postmenopausal women aged 50 to 79 years at entry that were recruited from 40 US clinical centers between 1993 and 1998 and followed prospectively.
  • The APOs evaluated were gestational diabetes, preeclampsia, hypertensivedisordr of pregnancy, preterm delivery (<37 weeks), low birth weight (<2,500 grams), and high birth weight (>4500 g). More than 1 APO may have occurred in the same woman, but not necessarily during the same pregnancy.
  • A total of 10,292 patients at an average age of 60 years responded to a questionnaire inquiring on past history of APO’s sent to their homes, and comprised of the study population. Of those, 3185 (31.0%) reported a history of 1 or more APOs, the most frequently reported being preterm delivery (14.7%), followed by low birth weight (13.8%), hypertensive disorder (7.4%), high birth weight (6.3%), and gestational diabetes (2.5%). The most common combination of APOs in the study population was preterm delivery and low birth weight (7.1%).
  • Baseline characteristics of the study participants at the time of responding to the questionnaires differed by the history and type of APO. Patients with history of any APO had a higher prevalence of risk factors such as higher BMI, coronary artery disease, hypertension, diabetes, smoking (>20 pack-years), history of stillbirth, lower levels of education and household income, younger age at first birth and older age at menopause, were less likely to have reported a history of breastfeeding, miscarriage, and menstrual cycle irregularity; and reported fewer live births.
  • Of the study cohort, 336 (3.3%) patients had a diagnosis of HF, 180 (1.8%) had HFpEF, and 111 (1.1%) had HFrEF (it is unclear if in the remaining 45 patients the EF was unavailable, or if they had HFmrEF) . Women with a history of APO had a higher rate of HF than those without a history of APO (3.8% vs 2.9%, statistical significance is not provided).
  • Women with history of hypertensive disorder of pregnancy, which was more common among black women, had the highest rate of HF (5.1%), and women with gestational diabetes had the lowest rate of HF (3.1%). Hypertensive disorder of pregnancy was the only APO with a significant association with HF in univariate models, and remained significantly associated with HF after adjusting for a model consisting of age, sociodemographic factors, smoking, randomization status, other subsequent APOs and reproductive history (OR, 1.75).
  • In analyses of HF subtypes, only history of hypertensive disorder of pregnancy was significantly associated with HFpEF in a fully adjusted model (OR, 2.06), but not with HFrEF.
  • There was no significant modification of the association of history of hypertensive disorder of pregnancy with HF by covariates including other APOs. Upon excluding women with history of coronary artery disease, the association between HDP and HF was similar

Dr. Yonatan Buber

Commentary from Dr. Yonatan (Seattle, USA), section editor of Cardio-Obstetrics Journal Watch:

The main strengths of the study are the large cohort included in it and the ability to identify outcomes and non-APO risk factors through the large and well established WHI database. The association between hypertensive disorder of pregnancy and the development of heart failure, which have been previously described in other works, are nicely reinforced by the authors, who also provide the mechanism for this association in their discussion.


Heart failure and hypertensive disorder of pregnancy have shared risk factors, such as chronic hypertension and obesity and which may underlie the association between hypertensive disorders of pregnancy and future occurrence of HF. In addition, hypertensive disorder of pregnancy, compared to normotensive pregnancies, was shown to be associated with several cardiac abnormalities that can lead to HF, including left ventricular remodeling and microvasculature changes, impaired diastolic function, and impaired coronary flow reserve.


Gestational diabetes was shown in prior works to be a pertinent risk factor for the development of HF, yet in this study this association has not been established. It is possible that the relatively low prevalence of gestational diabetes in the cohort included in this study is the main reason for this difference.


Limitations of the study include its retrospective nature with the associated survivorship bias among the included sample, who needed to survive until the APO survey was performed, the author’s inability to validate the obstetric records, and the inability to differentiate whether women had multiple APOs in the same pregnancy or in recurrent pregnancies.


In summary, in a large cohort of postmenopausal women included in the WHI registry, history of hypertensive disorders of pregnancy was the only APO associated with HF occurrence, primarily HFpEF . As stated by the authors, this represents an opportunity for early, aggressive, preventive interventions for HF and other CVD, possibly before development of the traditional risk factors (hypertension, diabetes, and obesity).