Pregnant women with preeclampsia as likely to develop heart disease as lifelong smokers

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 - PregnantExam

Preeclampsia could have a permanent, constricting effect on blood vessels of women who experience the hypertensive condition while pregnant, new research suggests.

Lead researcher Anna E. Stanhewicz, a post-doctoral fellow at Penn State’s College of Health and Human Development, compared 24 postpartum women—12 who experienced healthy pregnancies and 12 who suffered from preeclampsia—in an effort to determine whether blood vessels are permanently altered during a preeclamptic pregnancy. According to the study, recently published in Hypertension, Stanhewicz and co-authors predicted women who had preeclamptic pregnancies would exhibit increased sensitivity to the hormone angiotensin II, reduced endothelium-dependent dilation and reduced NO-mediated dilation in comparison with women who had healthy pregnancies. The team also hypothesized that losartan—a commercial drug used to treat high blood pressure—would increase endothelium-dependent vasodilation in preeclamptic patients.

Recent evidence that preeclampsia is linked to increased risk for cardiovascular disease (CVD) in women concluded mothers who develop preeclampsia are between two and seven times more likely to develop CVD and hypertension at a younger age than healthy pregnant women. They’re also more likely to die from CVD, Stanhewicz wrote.

Stanhewicz said she was prompted to study preeclampsia after reading a series of epidemiological papers that discussed the increased death risks.

“These papers showed that women who have had preeclampsia develop disease at an earlier age and with a greater frequency than women who have had a healthy pregnancy, and are as likely to develop CVD as someone who is a lifetime smoker,” she told Cardiovascular Business. “These findings were astounding to me, and as someone who studies CVD and is interested in prevention, I immediately wanted to work on this problem.”

To understand why preeclampsia is associated with increased CVD risk, Stanhewicz and her team turned to previous vascular studies in animals, who showed an increased vascular sensitivity to angiotensin II when exposed to preeclampsia.

The patients—who were all regularly active, nonhypertensive, nondiabetic nonsmokers—were initially evaluated through application of acetylcholine. Researchers were able to test the chemical locally on patients’ arms to determine how blood vessels just under the skin reacted to the substance. Stanhewicz found that when applied to women without previous preeclamptic pregnancies, acetylcholine caused their blood vessels to open up about 50 percent more than women who had experienced preeclampsia. When exposed to angiotensin II, blood vessels in women who'd had preeclampsia constricted about 20 percent more than their matched counterparts’.

According to the study, this meant women with preeclampsia were indeed more sensitive to angiotensin II than women without the condition.

“I was surprised by the magnitude of vascular dysfunction that we saw in women who had had preeclampsia,” Stanhewicz said. “To isolate the effects of the preeclamptic pregnancy we only included women who were otherwise healthy into the study, and because these women didn’t have any existing disease, I was anticipating a much smaller effect size. We found that despite their lack of traditional CVD risk factors, these women had an approximately 20 percent reduction in endothelial function, which is pretty large in this type of work.”

Stanhewicz’s team then applied losartan to inhibit the work of angiotensin II; it showed no effect in women who’d had healthy pregnancies, but improved blood vessel function in women who had had preeclamptic pregnancies.

In their paper, Stanhewicz and colleagues wrote this suggests that losartan could be an intervention strategy that would slow development of cardiovascular disease and CVD risk in women who experienced hypertensive pregnancies.

“I was really encouraged by the finding that if we locally inhibit the action of angiotensin II, we can improve endothelial function in these women,” Stanhewicz said. “I am now working on a series of follow-up studies which aim to explore ways we can inhibit this pathway to improve endothelial function in women who have had preeclampsia. Hopefully we can identify the best intervention strategies to prevent the progression of CVD in these women.”

She said the most important takeaways from her initial research were that women with preeclampsia do have reduced endothelial dysfunction, and an increased sensitivity to angiotensin II contributes to that dysfunction.

“Even though these women appear healthy and do not have any traditional CVD risk factors, we can already detect this dysfunction which precedes clinical CVD,” she said. “Knowing what contributes to this dysfunction gives us a better chance of applying the correct intervention strategies to prevent or slow the progression of CVD.”