Gestational HTN, Preeclampsia Worsen Long-Term Risk for Ischemic, Nonischemic Heart Failure

May 16, 2023

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

The risks were most pronounced, jumping more than sixfold 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 (CV) disease and a first successful pregnancy during which they either developed or did not experience gestational hypertension or preeclampsia.

It's 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 two HF etiologies, notes a report published May 10 in JACC: Heart Failure.

The adjusted risk for any HF during a median of 13 years after the pregnancy rose 70% for those who had developed gestational hypertension or preeclampsia. Their risk of nonischemic HF went up 60%, and their risk of 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 | Medscape Cardiology.

Obstetric history doesn't 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 cardiovascular risk factors regularly throughout life."

In many studies, she said, "knowledge of women-specific risk factors for cardiovascular disease 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 HF with preserved ejection fraction (HFpEF), which isn't closely related to a number of traditional CV risk factors.

Even though pregnancy complications such as gestational hypertension and preeclampsia don't 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 cardiovascular 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.

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 state.

Also, Bello said, the study's inclusion of patients with either gestational hypertension or preeclampsia may complicate its interpretation. Compared to 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."

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

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

Hazard ratios (HRs) for HF, ischemic HF, and nonischemic HF were significantly elevated over among the women with gestational hypertension or preeclampsia compared to those with normotensive pregnancies:

  • Any HF: HR, 1.70 (95% CI, 1.51 – 1.91)

  • Nonischemic HF: HR, 1.60 (95% CI, 1.40 – 1.83)

  • Ischemic HF: HR, 2.28 (95% CI, 1.74 – 2.98)

The analyses were adjusted 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 prior to 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 for HF developing 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, 2.00 – 12.34).

The study couldn't 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 heart failure might be driven by other factors, such as the inflammatory profile, endothelial dysfunction, and cardiac remodeling induced by preeclampsia or gestational hypertension."

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.

JACC Heart Fail. Published online May 10, 2023. Abstract

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