Preeclampsia, gestational hypertension drive long-term maternal CVD risk
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Women with a hypertensive disorder of pregnancy are 63% more likely to experience a CVD event in the decades after delivery compared with normotensive women, independent of shared risk factors like prepregnancy BMI and parental CVD history.
The relationship between hypertensive disorders of pregnancy and future maternal CVD has been well documented, but only a few previous studies were able to adjust for shared prepregnancy risk factors or examine these associations with average follow-up of more than 30 years after first birth, according to Jennifer J. Stuart, ScD, associate epidemiologist and instructor of medicine at Brigham and Women’s Hospital and Harvard Medical School.
“We found that 64% of the increased risk for CVD observed among women with a history of hypertensive disorders of pregnancy was jointly accounted for by the development of chronic hypertension, hypercholesterolemia, type 2 diabetes and weight gain after first birth,” Stuart told Healio. “Although the American Heart Association and American College of Cardiology endorsed preeclampsia and gestational hypertension as CV risk factors, women and their providers have lacked clear direction of what to do in the intervening years between delivery of a hypertensive pregnancy and the onset of CVD. Our mediation results provide four clear targets for screening and prevention efforts in women with a history of hypertensive pregnancy: BP, cholesterol and glucose levels, and BMI.”
Risk decades after delivery
Stuart and colleagues analyzed data from 60,379 parous women without CVD who participated in the ongoing Nurses’ Health Study II and were followed for incident CVD from first birth through 2017 (median follow-up since first birth, 34 years). Researchers estimated HRs for the relationship between a hypertensive disorder of pregnancy and CVD, adjusting for prepregnancy BMI, smoking and parental history of CVD.
“To evaluate the proportion of the association jointly accounted for by chronic hypertension, hypercholesterolemia, type 2 diabetes and changes in BMI, we used the difference method,” the researchers wrote.
Within the cohort, approximately 10% of women experienced a hypertensive disorder of pregnancy during their first pregnancy; first births occurred between 1964 and 2008 (mean age at first birth, 27 years). Women with a hypertensive disorder of pregnancy were three times as likely to have a prepregnancy BMI of at least 30 kg/m2 and were more likely to have a parent with a premature CVD event.
Preeclampsia vs. gestational hypertension
By the end of follow-up, 1.8% of women experienced a first CVD event, including 554 MI events, six fatal CAD events and 515 strokes. Researchers found that women with a hypertensive disorder of pregnancy during a first pregnancy were more likely to develop CVD (HR = 1.63; 95% CI, 1.37-1.94) compared with women with normotensive pregnancies. Established CVD risk factors mediated 64% of the risk. The increased rate of CVD was higher for preeclampsia (HR = 1.72; 95% CI, 1.42-2.1) compared with gestational hypertension (HR = 1.41; 95% CI, 1.03-1.93).
Established CVD risk factors accounted for 57% of the increased rate of CVD for preeclampsia but 84% for gestational hypertension (P for both < .0001).
“Perhaps the most novel contribution of this analysis was the discovery of subtype-specific associations and mediation results,” Stuart told Healio. “We found that the overall relationship between hypertensive disorders of pregnancy and CVD appears to be driven by underlying relationships between preeclampsia and coronary heart disease, and between gestational hypertension and stroke. We also found that established CVD risk factors accounted for more of the increased risk for CVD among women with a history of gestational hypertension than among women with a history of preeclampsia.”
Stuart said women with a history of gestational hypertension or preeclampsia should be informed that they are at increased risk for CVD, including stroke and MI.
Stuart said the findings show gestational hypertension and preeclampsia should be analyzed separately and not combined as a single exposure group.
“One question I am eager to answer is how to identify which women with a history of a hypertensive disorder of pregnancy will indeed go on to experience a CV event,” Stuart said. “There is no doubt that all women with hypertensive pregnancies could benefit from heart-healthy diet and other lifestyle changes after pregnancy, but these interventions will have the greatest individual impact on reducing risk for those at highest risk. There is more work to be done to identify who they are and what can help reduce their risk most effectively after a hypertensive pregnancy.”
Risk assessment during ‘fourth trimester’
In a related editorial, Garima V. Sharma, MD, FACC, FACP, assistant professor of medicine and director of the cardio-obstetrics program at Johns Hopkins University School of Medicine and a Cardiology Today Editorial Board Member, and colleagues wrote the findings highlight the importance of assessing women with a hypertensive disorder of pregnancy for CV risk after delivery.
“At minimum, clinicians need to be cognizant of this subgroup of women that might be under the radar of preventive cardiologists, internists and family practitioners,” Sharma and colleagues wrote. “This study also highlights the need for future studies focused on the mechanistic links between preeclampsia and long-term cardiovascular risk in diverse populations. The concept of a fourth trimester is a step forward in improving the transition of care between obstetricians and primary care providers, with extended postpartum care and frequent checkpoints to assess cardiometabolic risk factors and implement lifestyle interventions.”
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For more information:
Jennifer J. Stuart, ScD, can be reached at jjstuart@bwh.harvard.edu.
Perspective
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Natalie A. Bello, MD, MPH
This study by Stuart and colleagues is an important contribution to the existing knowledge base. The study not only confirmed the findings of prior studies and showed that women with a history of preeclampsia have a higher risk for future CVD than those with gestational hypertension, but it also extends our knowledge and demonstrates that established CVD risk factors accounted for 84% of the increased rate of CVD after gestational hypertension but only 57% in preeclampsia. I was intrigued by their finding that stroke risk was higher in individuals exposed to gestational hypertension than preeclampsia and wonder if this might be the result of selection bias; individuals with preeclampsia who had an early stroke were either disabled or died before being able to enroll in the NHS.
For me the most important takeaway messages are that we need to do a better job screening for, diagnosing and managing traditional CVD risk factors in individuals who experience an adverse pregnancy outcome to prevent disease. We must research the mechanisms through which risk enhancers like preeclampsia lead to CVD so we can develop strategies to mitigate that increased risk. We also need studies in more diverse populations that we know are disproportionately affected by adverse pregnancy outcomes.
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