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. 2024 Jun;81(6):1272-1284.
doi: 10.1161/HYPERTENSIONAHA.124.22905. Epub 2024 Apr 2.

Coronary Microvascular Function Following Severe Preeclampsia

Michael C Honigberg  1   2 , Katherine E Economy  3 , Maria A Pabón  4 , Xiaowen Wang  4 , Claire Castro  1 , Jenifer M Brown  4   5 , Sanjay Divakaran  4   5 , Brittany N Weber  4   5 , Leanne Barrett  5 , Anna Perillo  5 , Anina Y Sun  5 , Tajmara Antoine  1 , Faranak Farrohi  4 , Brenda Docktor  4 , Emily S Lau  1 , Doreen DeFaria Yeh  1 , Pradeep Natarajan  1   2 , Amy A Sarma  1 , Robert M Weisbrod  6 , Naomi M Hamburg  6 , Jennifer E Ho  7 , Jason D Roh  1 , Malissa J Wood  1   8 , Nandita S Scott  1 , Marcelo F Di Carli  4   5
Affiliations

Coronary Microvascular Function Following Severe Preeclampsia

Michael C Honigberg et al. Hypertension. 2024 Jun.

Abstract

Background: Preeclampsia is a pregnancy-specific hypertensive disorder associated with an imbalance in circulating proangiogenic and antiangiogenic 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 within 4 weeks of delivery. A control group of premenopausal, nonpostpartum women was also included. Myocardial flow reserve, myocardial blood flow, and coronary vascular resistance were compared across groups. sFlt-1 (soluble fms-like tyrosine kinase receptor-1) and PlGF (placental growth factor) were measured at imaging.

Results: The primary cohort included 19 women with severe preeclampsia (imaged at a mean of 15.3 days postpartum), 5 with normotensive pregnancy (mean, 14.4 days postpartum), and 13 nonpostpartum female controls. Preeclampsia was associated with lower myocardial flow reserve (β, -0.67 [95% CI, -1.21 to -0.13]; P=0.016), lower stress myocardial blood flow (β, -0.68 [95% CI, -1.07 to -0.29] mL/min per g; P=0.001), and higher stress coronary vascular resistance (β, +12.4 [95% CI, 6.0 to 18.7] mm Hg/mL per min/g; P=0.001) versus nonpostpartum controls. Myocardial flow reserve and coronary vascular resistance after normotensive pregnancy were intermediate between preeclamptic and nonpostpartum groups. Following preeclampsia, myocardial flow reserve was positively associated with time following delivery (P=0.008). The sFlt-1/PlGF ratio strongly correlated with rest myocardial blood flow (r=0.71; P<0.001), independent of hemodynamics.

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

Keywords: blood pressure; cardiovascular diseases; heart failure; preeclampsia; pregnancy.

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Conflict of interest statement

Disclosures M.C. Honigberg reports consulting fees from CRISPR Therapeutics and Comanche Biopharma, the advisory board service for Miga Health, and grant support from Genentech. J.M. Brown reports consulting fees from Bayer AG and AstraZeneca. B.N. Weber reports advisory board service for Novo Nordisk, Horizon Therapeutics, Kinsika Pharmaceuticals, and Aegpha. E.S. Lau reports previous advisory board service for Astellas Pharma. P. Natarajan reports research grants from Allelica, Apple, Amgen, Boston Scientific, Genentech/Roche, and Novartis, personal fees from Allelica, Apple, AstraZeneca, Blackstone Life Sciences, Foresite Labs, Genentech/Roche, GV, HeartFlow, Magnet Biomedicine, and Novartis, scientific advisory board membership of Esperion Therapeutics, Preciseli, and TenSixteen Bio, equity in Preciseli and TenSixteen Bio, and spousal employment at Vertex Pharmaceuticals and is a scientific co-founder of TenSixteen Bio, all unrelated to the present work. N.M. Hamburg reports consulting fees from Merck, Boston Scientific, and Novo Nordisk, all unrelated to the present work. M.F. Di Carli reports grant support from Gilead Sciences, in-kind research support from Amgen, and consulting fees from Sanofi, MedTrace Pharma, and Vale Health. The other authors report no conflicts.

Figures

Figure 1.
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.
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.
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.
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