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CME / ABIM MOC / CE

Are Hypertensive Disorders of Pregnancy Associated With Heart Failure?

  • Authors: News Author: Steve Stiles, MS; CME Author: Charles P. Vega, MD 
  • CME / ABIM MOC / CE Released: 6/21/2023
  • Valid for credit through: 6/21/2024, 11:59 PM EST
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Target Audience and Goal Statement

This activity is intended for primary care clinicians, obstetrician gynecologists, cardiologists, nurses/nurse practitioners, pharmacists, physician assistants, and other clinicians who care for women with pregnancy-induced hypertension (PIH).

The goal of this activity is for learners to be better able to evaluate the relationship between PIH and maternal heart failure (HF).

Upon completion of this activity, participants will:

  • Distinguish maternal cardiovascular outcomes associated with preeclampsia
  • Evaluate the relationship between PIH and maternal HF
  • Outline implications for the healthcare team


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News Author

  • Steve Stiles, MS

    Freelance writer, Medscape

    Disclosures

    Steve Stiles, MS, has no relevant financial relationships.

CME Author

  • Charles P. Vega, MD

    Health Sciences Clinical Professor of Family Medicine
    University of California, Irvine School of Medicine

    Disclosures

    Charles P. Vega, MD, has the following relevant financial relationships:
    Consultant or advisor for: Boehringer Ingelheim Pharmaceuticals, Inc.; GlaxoSmithKline; Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Editor/Compliance Reviewer

  • Amanda Jett, PharmD, BCACP

    Associate Director, Accreditation and Compliance, Medscape, LLC

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    Amanda Jett, PharmD, BCACP, has no relevant financial relationships.

Nurse Planner

  • Stephanie Corder, ND, RN, CHCP

    Associate Director, Accreditation and Compliance, Medscape, LLC

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    Stephanie Corder, ND, RN, CHCP, has no relevant financial relationships.

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This activity has been peer reviewed and the reviewer has no relevant financial relationships.


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CME / ABIM MOC / CE

Are Hypertensive Disorders of Pregnancy Associated With Heart Failure?

Authors: News Author: Steve Stiles, MS; CME Author: Charles P. Vega, MD Faculty and Disclosures

CME / ABIM MOC / CE Released: 6/21/2023

Valid for credit through: 6/21/2024, 11:59 PM EST

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Clinical Context

Between 5% and 10% of pregnancies are complicated by pregnancy-induced hypertension disorders, and pregnancy-induced hypertension (PIH) frequently resolves after delivery; however, pregnancy represents a physiological “stress test” for women, and a meta-analysis by Wu and colleagues assessed the risk for cardiovascular (CV) disorders associated with preeclampsia, specifically. Their research was published in the February 22, 2017 issue of Circulation: Cardiovascular Quality and Outcomes.[1]

Researchers drew on 22 studies, which included more than 258,000 women with preeclampsia. After adjustment for confounding variables, the adjusted risk ratio (aRR) for coronary heart disease (CHD) associated with preeclampsia during pregnancy vs no preeclampsia was 2.5 (95% CI: 1.43, 4.37), and the respective aRR for stroke was 1.81 (95% CI: 1.29, 2.55). Preeclampsia was also independently associated with a higher risk for CV death (aRR 2.21 [95% CI: 1.83, 2.66]).

These findings are remarkable and should be discussed routinely with patients with PIH; however, the most significant CV risk associated with preeclampsia in this study was for heart failure (HF) (aRR 4.19 [95% CI: 2.09, 8.38]). Still, there remain questions regarding the relationship between PIH and HF, including whether PIH increases the risk for ischemic HF, nonischemic HF, or both. The current study by Mantel and colleagues seeks answers to these questions.

Study Synopsis and Perspective

Women who experienced gestational hypertension or preeclampsia are at increased risk of developing nonischemic HF and especially ischemic HF over the next decade or two, an observational study suggests.

The risks were most pronounced, jumping more than 6-fold in the case of ischemic HF, during the first 6 years after the pregnancy. They then receded to plateau at a lower, still significantly elevated level of risk that persisted even years later, in the analysis of women in a Swedish medical birth registry.

The case-matching study compared women with no history of cardiovascular disease (CVD) and a first successful pregnancy during which they either developed or did not experience gestational hypertension or preeclampsia.

It is among the first studies to explore the impact of pregnancy-induced hypertensive disease on subsequent HF risk separately for both ischemic and nonischemic HF and to find that the severity of such risk differs for the 2 HF etiologies, noted a report published May 10 in JACC: Heart Failure.[2]

The adjusted risk for any HF during a median of 13 years after the pregnancy rose 70% for women who had developed gestational hypertension or preeclampsia. Their risk for nonischemic HF went up 60%, and their risk for ischemic HF more than doubled.

Hypertensive disorders of pregnancy "are so much more than short-term disorders confined to the pregnancy period. They have long-term implications throughout a lifetime," lead author Ängla Mantel, MD, PhD, told theheart.org | Medscape Cardiology.

Obstetric history does not figure into any formal HF risk scoring systems, observed Mantel, Karolinska Institutet, Stockholm, Sweden. Still, women who develop gestational hypertension, preeclampsia, or other pregnancy complications "should be considered a high-risk population even after the pregnancy and monitored for [CV] risk factors regularly throughout life."

In many studies, she said, "knowledge of women-specific risk factors for [CVD] is poor among both clinicians and patients."

The current findings should help raise awareness about such obstetric risk factors for HF, "especially" in patients with heart failure with preserved ejection fraction (HFpEF), which is not closely related to a number of traditional CV risk factors.

Even though pregnancy complications, such as gestational hypertension and preeclampsia, do not feature in risk calculators, "they are actually risk enhancers per the 2019 primary prevention guidelines," observed Natalie A. Bello, MD, MPH, who was not involved in the current study, in an interview.

"We're working to educate physicians and [CV] team members to take a pregnancy history for risk stratification of women in primary prevention," said Bello, who is director of hypertension research at the Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California.

The current study, she said, "is an important step" for its finding that hypertensive disorders of pregnancy are associated separately with both ischemic and nonischemic HF.

She pointed out, however, that because the study excluded women with peripartum cardiomyopathy, a form of nonischemic HF, it may "underestimate the impact of hypertensive disorders on the short-term risk of nonischemic heart failure."

Women who had peripartum cardiomyopathy were excluded to avoid misclassification of other HF outcomes, the authors stated.

Also, Bello said, the study's inclusion of patients with either gestational hypertension or preeclampsia may complicate its interpretation. Compared with the former condition, she said, preeclampsia "involves more inflammation and more endothelial dysfunction. It may cause a different impact on the heart and the vasculature."

The analysis identified about 79,000 women with gestational hypertension or preeclampsia among more than 1.4 million primiparous women who entered the Swedish Medical Birth Register over a period of about 30 years. The researchers matched these women with about 396,000 women in the registry who had normotensive pregnancies.

The study excluded, besides women with peripartum cardiomyopathy, women with a prepregnancy history of HF, hypertension, ischemic heart disease, atrial fibrillation, or valvular heart disease.

Hazard ratios for HF, ischemic HF, and nonischemic HF were significantly elevated among the women with gestational hypertension or preeclampsia compared with women with normotensive pregnancies:

  • Any HF: adjusted hazard ratio (aHR) 1.7 (95% CI: 1.51, 1.91)
  • Nonischemic HF: aHR 1.6 (95% CI: 1.4, 1.83)
  • Ischemic HF: aHR 2.28 (95% CI: 1.74, 2.98)

The investigators adjusted the analyses for maternal age at delivery, year of delivery, prepregnancy comorbidities, maternal education level, smoking status, and body mass index.

Sharper risk increases were seen among women with gestational hypertension or preeclampsia who delivered before gestational week 34:

  • Any HF: HR 2.46 (95% CI: 1.82, 3.32)
  • Nonischemic HF: HR 2.33 (95% CI: 1.65, 3.31)
  • Ischemic HF: HR 3.64 (95% CI: 1.97, 6.74)

Risks of developing HF within 6 years of pregnancy, characterized by gestational hypertension or preeclampsia, were far more pronounced for ischemic HF than for nonischemic HF:

  • Any HF: HR 2.09 (95% CI: 1.52, 2.89)
  • Nonischemic HF: HR 1.86 (95% CI: 1.32, 2.61)
  • Ischemic HF: HR 6.52 (95% CI: 2, 12.34)

The study could not directly explore potential mechanisms for the associations between pregnancy-induced hypertensive disorders and different forms of HF, but it may have provided clues, Mantel said.

The hypertensive disorders and ischemic HF appear to share risk factors that could lead to both conditions, she noted. Also, hypertension itself is a risk factor for ischemic heart disease.

In contrast, "the risk of nonischemic HF might be driven by other factors, such as the inflammatory profile, endothelial dysfunction, and cardiac remodeling induced by preeclampsia or gestational hypertension," according to the researchers.

Those disorders, moreover, are associated with cardiac structural changes that are also seen in HFpEF, Mantel said, and both HFpEF and preeclampsia are characterized by systemic inflammation and endothelial dysfunction.

"These pathophysiological similarities," she proposed, "might explain the link between pregnancy-induced hypertensive disorder and HFpEF."

The authors have disclosed no relevant financial relationships. Bello has received grants from the National Institutes of Health.

Study Highlights

  • Investigators drew study data from a national birth registry in Sweden, which contains information on > 98% of live births there since 1973.
  • The study cohort included primiparous women who gave birth between 1988 and 2019. The analysis excluded women with a history of HF before pregnancy, along with women with a past history of hypertension or other heart disease.
  • Researchers identified women with a history of PIH, preeclampsia, or eclampsia through diagnosis codes. They matched women with PIH with primiparous women without PIH according to age and year of delivery in the study analysis.
  • The main study outcome was the diagnosis of HF ≥ 6 months after delivery. Researchers classified the HF as ischemic or nonischemic.
  • The study analysis was adjusted to account for maternal age, comorbid illnesses, educational attainment, smoking status, and body mass index during pregnancy.
  • The investigators compared 79,334 women with PIH with 396,531 women without PIH. Obesity in early pregnancy was nearly twice as common among women with PIH vs control participants, whereas prepregnancy diabetes was nearly 5 times more common in the PIH cohort. Finally, twin births were about 3 times more common in the PIH group.
  • The rates of preterm delivery in the PIH and control cohorts were 19.5% and 6%, respectively. The respective rates of small-for-gestational age infants were 12% and 3%.
  • The median follow-up time for HF was 13.2 years. The rates of HF in the PIH and control groups were 3.3 and 1.8 cases per 10,000 person-years, respectively (aHR 1.7 [95% CI: 1.51, 1.91]).
  • The HR for nonischemic HF in comparing the PIH and control groups was 1.6 (95% CI: 1.4, 1.83). The respective HR for ischemic HF was 2.08 (95% CI: 1.44, 3).
  • The median times to the diagnosis of nonischemic and ischemic HF were 16 and 20 years, respectively. The median age at the time of HF diagnosis was between 45 and 50 years.
  • Preterm delivery before 34 weeks of gestation was associated with a HR of 2.46 (95% CI: 1.82, 3.32) for HF and was significant for both nonischemic and ischemic HF. Premature delivery combined with PIH appeared synergistic in increasing the risk for HF.
  • Gestational hypertension was associated with a higher risk for HF compared with preeclampsia.
  • The association between PIH and a higher risk for HF was strongest during the first 6 years after PIH. Thereafter, the association between PIH and HF weakened but always remained significant.

Implications for the Healthcare Team

  • A previous meta-analysis by Wu and colleagues demonstrated that preeclampsia was associated with higher risks for HF, CHD, stroke, and CV death.
  • The current study by Mantel and colleagues demonstrates that PIH is associated with a higher risk for both nonischemic and ischemic HF. Although the association between PIH and a higher risk for HF was strongest during the first 6 years after PIH, it remained significant throughout the follow-up period.
  • The healthcare team should encourage cardiovascular prevention and symptom monitoring among women with a history of PIH.

 

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