Hypertension and persistent inflammation with prior preeclampsia

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Women with a prior preeclampsia pregnancy have a significantly higher incidence of hypertension in the postpartum period, compared to women with a normotensive pregnancy, according to a study.

The study, which was presented virtually at the Society for Maternal-Fetal Medicine’s (SMFM) 41st Annual Pregnancy Meeting, also found that following preeclampsia, anti-inflammatory T-cell cytokines continue to be suppressed in the early postpartum period of 1 to 3 years, creating an inflammatory milieu.

At 8 to 10 years postpartum, the suppressed anti-inflammatory environment is further exacerbated by elevated levels of proinflammatory interleukin 6 (IL-6) and tumor necrosis factor alpha (TNFa).

“A history of preeclampsia is a risk factor for future cardiovascular disease (CVD), similar to chronic hypertension and obesity,” said principal investigator Mark Santillan, MD, PhD, an associate professor of maternal fetal medicine at the University of Iowa in Iowa City. “In women with a history of preeclampsia, 52% develop chronic, long-term hypertension, which is a major contributor to future CVD.”

While the association of preeclampsia and future CVD is clear, the biologic and molecular mechanisms are not, according to Santillan. “This knowledge gap drove our study,” he said.

The study, which began in July 2018, de-identified and coded plasma samples from women with either early onset of hypertension (n = 93) or late onset of hypertension (n = 58) after a normotensive or preeclampsia- effected pregnancy.

Samples were obtained from the Magee-Women’s Research Institute and Foundation in Pittsburgh, Pennsylvania, or the University of Iowa Maternal-Fetal Tissue Bank.

Women with prior preeclampsia had a higher rate of hypertension in both the early and late postpartum period compared to women with a normotensive pregnancy: 24% and 65% vs. 5% and 17%, respectively.

Hypertension in the early and late postpartum periods were associated with an orders of magnitude reduction in concentrations of anti-inflammatory cytokines IL-4, IL-10 and transforming growth factor beta (TGF-B) in women with a prior preeclampsia pregnancy.

Yet, only in the late postpartum period (8 to 10 years after the preeclamptic event) do proinflammatory IL-6 and TNFa significantly elevate in women with prior preeclampsia compared to women with a normotensive pregnancy.

“We anticipated that women with a history of preeclampsia in the early postpartum and late postpartum years would exhibit higher rates of low to moderate hypertension in comparison to women with no history of preeclampsia,” Santillan told Contemporary OB/GYN. “But what surprised our team is the immunologic environment associated with the hypertension during these different timepoints.”

The investigators also did not expect that in the early postpartum period there would be a reduction in the anti-inflammatory response, with no elevated proinflammatory milieu linked to hypertension after preeclampsia. “Likewise, in the late postpartum period, we did not anticipate an elevated proinflammatory milieu along with a loss of the anti-inflammatory response in circulation,” Santillan said.

Study results suggest that long-term hypertension and CVD in women who have been affected by preeclampsia may be associated with a loss of a counter-regulatory immunologic response. “While we are currently investigating the cellular and molecular mechanisms surrounding these differential immunologic responses related to preeclampsia and CVD, the results of our study begin to open the door for the investigation of novel postpartum agents and clinical protocols that may prevent future CVD,” Santillan said.

Given the study’s data and data from other sources, “I anticipate we will eventually have novel tools in our clinical toolbox to effectively prevent CVD related to hypertensive diseases in pregnancy,” he said.

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Disclosures

Santillan holds several patents focused on the prediction, diagnosis and treatment of preeclampsia.