Hypertensive Disorders of Pregnancy Linked to Increased Heart Failure Risk

An analysis of data from the Women's Health Initiative suggests a history of hypertensive disorders of pregnancy was associated with an almost doubling in odds of developing heart failure later in life.

A recent study from an international team of investigators suggests postmenopausal women with a history of adverse pregnancy outcomes could be at an increased risk of heart failure.

An analysis of the Women’s Health Initiative (WHI), results of the study demonstrate hypertensive disorders of pregnancy were independently associated with increased risk of incident heart failure, but this association was not observed for other adverse pregnancy outcomes, such as gestational diabetes, low birth weight, and preterm delivery.

“In this large cohort study of postmenopausal women, a history of HDP was independently associated with a 1.75-fold odds of developing subsequent heart failure. This association was significant after adjustment for multiple confounding factors, including other APOs, without evidence of modification by sociodemographic or reproductive factors or comorbidities,” wrote investigators.

With the intent of developing a more thorough understanding of the risks surrounding incident heart failure in women, a team led by Nisha Parikh, MD, MPH, of the University of San Francisco, carried out a cohort study using data from within the Women’s Health Initiative. The study was designed with the intent of assessing associations between 5 adverse pregnancy outcomes and incident adjudicated heart failure. The adverse pregnancy outcomes of interest were gestational diabetes, hypertensive disorders of pregnancy, low birth weight high birth weight, and preterm delivery.

Of the 161,808 women included in WHI, 44,174 participants were included in an incident heart failure subcohort. The cohort of interest for the current study was women who had completed the 2017 follow-up survey, which assessed adverse pregnancy outcomes. Investigators identified 10,292 women who had a history of pregnancy lasting for more than 6 months and responded to the 2017 survey for inclusion in their analyses.

Of note, the 2017 WHI follow-up survey was administered to all surviving WHI participants and included 6 questions related to adverse pregnancy outcomes, with possible responses of yes, no, and I do not know. This survey defined preterm delivery as less than 37 weeks gestation, low birth weight as less than 5.5 pounds, and high birth weight as more than 9 pounds and 14 ounces.

The study cohort had a mean age of 60 (IQR, 55-64) years, 3185 women who reported 1 or more adverse pregnancy outcome, and 336 with a diagnosis of incident heart failure. The cohort of women heart failure included 180 with HFpEF and 111 with HFrEF. Women who reported any adverse pregnancy outcomes ewer more likely to have hypertension, diabetes, coronary heart disease, or report smoking compared to their counterparts who did not report pregnancy outcomes.

The most commonly reported adverse pregnancy outcome was preterm delivery (n=1509), followed by low birth weight (n=1424), hypertensive disorders of pregnancy (n=759), high birth weight (n=644), and gestational diabetes (n=260). The most common combination of adverse pregnancy outcomes was preterm delivery and low birth weight, which was reported by 732 women.

Logistic regression was used to evaluate the association of each adverse pregnancy outcome with incident heart failure. Investigators noted testing was performed using both unadjusted and fully adjusted models. Further analysis was planned to assess associations with specific heart failure subtypes.

Upon analysis, only hypertensive disorders of pregnancy was significantly associated with heart failure in fully adjusted models (OR, 1.75; 95% CI, 1.22 to 2.50). When assessing heart failure subtypes, results incited hypertensive disorders of pregnancy was associated with HFpEF (OR, 2.06; 955 CI, 1.29 to 3.27), but not HFrEF (OR, 1.17; 95% CI, 0.59 to 2.30). In mediation analysis, results suggested hypertension explained 24% (95% CI, 12 to 73) of the association with hypertensive disorders of pregnancy with heart failure, coronary heart disease explained 23% (95% CI, 11 to 68), BMI explained 20% (95% CI, 10 to 64), and diabetes explained 1% (95% CI, -3.6 to 7.3).

“Further research is needed to better understand the potential mechanisms that link HDP with later development of HF. Dedicated studies are needed to establish effective interventions to mitigate long-term risk of HF and other CVD in women with APOs,” added investigators in their conclusion.

This study, “Adverse Pregnancy Outcomes and Incident Heart Failure in the Women’s Health Initiative,” was published in JAMA Network Open.