Endothelial dysfunction as a long-term effect of late onset hypertensive pregnancy disorders: High BMI is key

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

OBJECTIVE: Hypertensive disorders during pregnancy increase cardiovascular risk later in life by 2 to 9-fold. Endothelial activation is one of the underlying mechanisms of cardiovascular risk. Therefore, we decided to investigate endothelial activation in primiparous women, 2.5 years after a hypertensive pregnancy disorder.

STUDY DESIGN: Plasma samples were taken from women 2.5 years after gestational hypertension (GH) or late onset preeclampsia (cases) and from women 2.5 years after a normotensive pregnancy (controls). We studied the effects of patient plasma on the endothelial barrier function of primary human umbilical vein endothelial cells (HUVECs) using Electric Cell-Substrate Impedance Sensing (ECIS) and we measured levels of endothelial activation markers soluble intercellular adhesion molecule 1 (sICAM-1) and soluble endothelial selectin (sE-selectin) in the plasma samples of patients.

RESULTS: Plasma from primiparous women with a history of late onset preeclampsia disrupted the endothelial barrier more than plasma from women with a history of GH. Endothelial resistance was reduced by 22% in samples taken after preeclampsia, 16% after normotensive pregnancy and 3% after GH (p ≤ 0.0001 GH versus preeclampsia and p = 0.0003 versus normotensive pregnancy). We did not find differences in the levels of soluble endothelial activation markers (sICAM-1 p = 0.326 and sE-selectin p = 0.978). However, the BMI ≥25 showed a strong correlation with increased levels of sICAM-1 (p = 0.046) and sE-selectin (p = 0.002).

CONCLUSION: Our results indicate that GH and late onset preeclampsia are distinct disease entities with a different pathogenic mechanism underlying their cardiovascular risk. Furthermore, this study supports the hypothesis that these two diseases are early manifestations of cardiovascular vulnerability due to an unfavorable risk profile, and that obesity plays a main role. Our results suggest that this high-risk female population would be eligible for preventive care.

LanguageEnglish
Pages62-69
Number of pages8
JournalEuropean Journal of Obstetrics and Gynecology and Reproductive Biology
Volume225
DOIs
Publication statusPublished - Jun 2018

Cite this

@article{b45f527da0f44f63a9ea006cc99d74f3,
title = "Endothelial dysfunction as a long-term effect of late onset hypertensive pregnancy disorders: High BMI is key",
abstract = "OBJECTIVE: Hypertensive disorders during pregnancy increase cardiovascular risk later in life by 2 to 9-fold. Endothelial activation is one of the underlying mechanisms of cardiovascular risk. Therefore, we decided to investigate endothelial activation in primiparous women, 2.5 years after a hypertensive pregnancy disorder.STUDY DESIGN: Plasma samples were taken from women 2.5 years after gestational hypertension (GH) or late onset preeclampsia (cases) and from women 2.5 years after a normotensive pregnancy (controls). We studied the effects of patient plasma on the endothelial barrier function of primary human umbilical vein endothelial cells (HUVECs) using Electric Cell-Substrate Impedance Sensing (ECIS) and we measured levels of endothelial activation markers soluble intercellular adhesion molecule 1 (sICAM-1) and soluble endothelial selectin (sE-selectin) in the plasma samples of patients.RESULTS: Plasma from primiparous women with a history of late onset preeclampsia disrupted the endothelial barrier more than plasma from women with a history of GH. Endothelial resistance was reduced by 22{\%} in samples taken after preeclampsia, 16{\%} after normotensive pregnancy and 3{\%} after GH (p ≤ 0.0001 GH versus preeclampsia and p = 0.0003 versus normotensive pregnancy). We did not find differences in the levels of soluble endothelial activation markers (sICAM-1 p = 0.326 and sE-selectin p = 0.978). However, the BMI ≥25 showed a strong correlation with increased levels of sICAM-1 (p = 0.046) and sE-selectin (p = 0.002).CONCLUSION: Our results indicate that GH and late onset preeclampsia are distinct disease entities with a different pathogenic mechanism underlying their cardiovascular risk. Furthermore, this study supports the hypothesis that these two diseases are early manifestations of cardiovascular vulnerability due to an unfavorable risk profile, and that obesity plays a main role. Our results suggest that this high-risk female population would be eligible for preventive care.",
keywords = "Adult, Biomarkers/blood, Body Mass Index, Cardiovascular Diseases/blood, E-Selectin/blood, Endothelium, Vascular/physiopathology, Female, Humans, Hypertension, Pregnancy-Induced/blood, Intercellular Adhesion Molecule-1/blood, Pregnancy, Risk Factors",
author = "Alma, {L J} and {De Groot}, {C J M} and {De Menezes}, {R X} and W Hermes and Hordijk, {P L} and I Kovačević",
note = "Copyright {\circledC} 2018 Elsevier B.V. All rights reserved.",
year = "2018",
month = "6",
doi = "10.1016/j.ejogrb.2018.04.003",
language = "English",
volume = "225",
pages = "62--69",
journal = "European Journal of Obstetrics and Gynecology and Reproductive Biology",
issn = "0301-2115",
publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - Endothelial dysfunction as a long-term effect of late onset hypertensive pregnancy disorders

T2 - European Journal of Obstetrics and Gynecology and Reproductive Biology

AU - Alma, L J

AU - De Groot, C J M

AU - De Menezes, R X

AU - Hermes, W

AU - Hordijk, P L

AU - Kovačević, I

N1 - Copyright © 2018 Elsevier B.V. All rights reserved.

PY - 2018/6

Y1 - 2018/6

N2 - OBJECTIVE: Hypertensive disorders during pregnancy increase cardiovascular risk later in life by 2 to 9-fold. Endothelial activation is one of the underlying mechanisms of cardiovascular risk. Therefore, we decided to investigate endothelial activation in primiparous women, 2.5 years after a hypertensive pregnancy disorder.STUDY DESIGN: Plasma samples were taken from women 2.5 years after gestational hypertension (GH) or late onset preeclampsia (cases) and from women 2.5 years after a normotensive pregnancy (controls). We studied the effects of patient plasma on the endothelial barrier function of primary human umbilical vein endothelial cells (HUVECs) using Electric Cell-Substrate Impedance Sensing (ECIS) and we measured levels of endothelial activation markers soluble intercellular adhesion molecule 1 (sICAM-1) and soluble endothelial selectin (sE-selectin) in the plasma samples of patients.RESULTS: Plasma from primiparous women with a history of late onset preeclampsia disrupted the endothelial barrier more than plasma from women with a history of GH. Endothelial resistance was reduced by 22% in samples taken after preeclampsia, 16% after normotensive pregnancy and 3% after GH (p ≤ 0.0001 GH versus preeclampsia and p = 0.0003 versus normotensive pregnancy). We did not find differences in the levels of soluble endothelial activation markers (sICAM-1 p = 0.326 and sE-selectin p = 0.978). However, the BMI ≥25 showed a strong correlation with increased levels of sICAM-1 (p = 0.046) and sE-selectin (p = 0.002).CONCLUSION: Our results indicate that GH and late onset preeclampsia are distinct disease entities with a different pathogenic mechanism underlying their cardiovascular risk. Furthermore, this study supports the hypothesis that these two diseases are early manifestations of cardiovascular vulnerability due to an unfavorable risk profile, and that obesity plays a main role. Our results suggest that this high-risk female population would be eligible for preventive care.

AB - OBJECTIVE: Hypertensive disorders during pregnancy increase cardiovascular risk later in life by 2 to 9-fold. Endothelial activation is one of the underlying mechanisms of cardiovascular risk. Therefore, we decided to investigate endothelial activation in primiparous women, 2.5 years after a hypertensive pregnancy disorder.STUDY DESIGN: Plasma samples were taken from women 2.5 years after gestational hypertension (GH) or late onset preeclampsia (cases) and from women 2.5 years after a normotensive pregnancy (controls). We studied the effects of patient plasma on the endothelial barrier function of primary human umbilical vein endothelial cells (HUVECs) using Electric Cell-Substrate Impedance Sensing (ECIS) and we measured levels of endothelial activation markers soluble intercellular adhesion molecule 1 (sICAM-1) and soluble endothelial selectin (sE-selectin) in the plasma samples of patients.RESULTS: Plasma from primiparous women with a history of late onset preeclampsia disrupted the endothelial barrier more than plasma from women with a history of GH. Endothelial resistance was reduced by 22% in samples taken after preeclampsia, 16% after normotensive pregnancy and 3% after GH (p ≤ 0.0001 GH versus preeclampsia and p = 0.0003 versus normotensive pregnancy). We did not find differences in the levels of soluble endothelial activation markers (sICAM-1 p = 0.326 and sE-selectin p = 0.978). However, the BMI ≥25 showed a strong correlation with increased levels of sICAM-1 (p = 0.046) and sE-selectin (p = 0.002).CONCLUSION: Our results indicate that GH and late onset preeclampsia are distinct disease entities with a different pathogenic mechanism underlying their cardiovascular risk. Furthermore, this study supports the hypothesis that these two diseases are early manifestations of cardiovascular vulnerability due to an unfavorable risk profile, and that obesity plays a main role. Our results suggest that this high-risk female population would be eligible for preventive care.

KW - Adult

KW - Biomarkers/blood

KW - Body Mass Index

KW - Cardiovascular Diseases/blood

KW - E-Selectin/blood

KW - Endothelium, Vascular/physiopathology

KW - Female

KW - Humans

KW - Hypertension, Pregnancy-Induced/blood

KW - Intercellular Adhesion Molecule-1/blood

KW - Pregnancy

KW - Risk Factors

U2 - 10.1016/j.ejogrb.2018.04.003

DO - 10.1016/j.ejogrb.2018.04.003

M3 - Article

VL - 225

SP - 62

EP - 69

JO - European Journal of Obstetrics and Gynecology and Reproductive Biology

JF - European Journal of Obstetrics and Gynecology and Reproductive Biology

SN - 0301-2115

ER -