Coronary Microvascular Function Following Severe Preeclampsia

Abstract

Background: Preeclampsia is a pregnancy-specific hypertensive disorder associated with an imbalance in circulating pro- and anti-angiogenic proteins. Preclinical evidence implicates microvascular dysfunction as a potential mediator of preeclampsia-associated cardiovascular risk.

Methods: Women with singleton pregnancies complicated by severe antepartum-onset preeclampsia and a comparator group with normotensive deliveries underwent cardiac positron emission tomography (PET) within 4 weeks of delivery. A control group of pre-menopausal, non-postpartum women was also included. Myocardial flow reserve (MFR), myocardial blood flow (MBF), and coronary vascular resistance (CVR) were compared across groups. Soluble fms-like tyrosine kinase receptor-1 (sFlt-1) and placental growth factor (PlGF) were measured at imaging.

Results: The primary cohort included 19 women with severe preeclampsia (imaged at a mean 16.0 days postpartum), 5 with normotensive pregnancy (mean 14.4 days postpartum), and 13 non-postpartum female controls. Preeclampsia was associated with lower MFR (β=-0.67 [95% CI -1.21 to -0.13]; P=0.016), lower stress MBF (β=-0.68 [95% CI, -1.07 to -0.29] mL/min/g; P=0.001), and higher stress CVR (β=+12.4 [95% CI 6.0 to 18.7] mmHg/mL/min/g; P=0.001) vs. non-postpartum controls. MFR and CVR after normotensive pregnancy were intermediate between preeclamptic and non-postpartum groups. Following preeclampsia, MFR was positively associated with time following delivery (P=0.008). The sFlt-1/PlGF ratio strongly correlated with rest MBF (r=0.71; P<0.001), independent of hemodynamics.

Conclusions: In this exploratory study, we observed reduced coronary microvascular function in the early postpartum period following severe preeclampsia, suggesting that systemic microvascular dysfunction in preeclampsia involves the coronary microcirculation. Further research is needed to establish interventions to mitigate risk of preeclampsia-associated cardiovascular disease.

Keywords: cardiac positron emission tomography; coronary microvascular function; preeclampsia; pregnancy; women’s health.

Figure 1.. Severe preeclampsia is associated with reduced myocardial flow reserve in the early postpartum period.

(A) Myocardial flow reserve by group. (B) Difference in myocardial flow reserve among postpartum women with severe preeclampsia and normotensive postpartum women vs. non-postpartum controls. Women with severe preeclampsia (n=19) underwent PET imaging at a mean (SD) 15.3 (7.6) days postpartum; normotensive postpartum women (n=5) underwent PET imaging at 14.4 (8.4) days postpartum. Non-postpartum women (n=13) constituted the reference group. Myocardial flow reserve was significantly reduced among women following delivery with severe preeclampsia.

Figure 2.. (A) Myocardial flow reserve and (B) rest myocardial blood flow vs. time following delivery among women with preeclampsia.

Women with severe preeclampsia (n=19) underwent PET imaging at a mean (SD) 15.3 (7.6) days postpartum (overall range: 2–30 days). Myocardial flow reserve appeared to increase, and rest myocardial blood draw appeared to decrease, with time following delivery.

Figure 3.. Correlation of (A) myocardial flow reserve and (B) rest myocardial blood flow with the sFlt-1/PlGF ratio among women with preeclampsia.

Myocardial flow reserve was moderately inversely associated, and rest myocardial blood flow strongly positive correlated, with the sFlt-1/PlGF ratio among postpartum women with preeclampsia (n=19). sFlt-1 indicates soluble fms-like tyrosine kinase receptor-1. PlGF indicates placental growth factor.