Hypertensive Disorders of Pregnancy and Long-Term Maternal Cardiovascular and Metabolic Biomarkers

Ashley N. Battarbee; Lisa Mele; Mark B. Landon; Michael W. Varner; Brian M. Casey; Uma M. Reddy; Ronald J. Wapner; Dwight J. Rouse; John M. Thorp; Edward K. Chien; George Saade; Alan M. Peaceman; Sean C. Blackwell; for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network

doi:10.1055/a-2096-0443

American Journal of Perinatology, Table of Contents

Am J Perinatol 2024; 41(S 01): e1976-e1981
DOI: 10.1055/a-2096-0443

Original Article

Hypertensive Disorders of Pregnancy and Long-Term Maternal Cardiovascular and Metabolic Biomarkers

Ashley N. Battarbee

¹Departments of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, University of Alabama at Birmingham, Birmingham, Alabama

,

Lisa Mele

²George Washington University Biostatistics Center, Washington, District of Columbia

,

Mark B. Landon

³Department of Obstetrics and Gynecology, The Ohio State University College of Medicine, Columbus, Ohio

,

Michael W. Varner

⁴Department of Obstetrics and Gynecology, University of Utah Health Sciences Center, Salt Lake City, Utah

,

Brian M. Casey

⁵Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas

,

Uma M. Reddy

⁶Department of Obstetrics and Gynecology, Eunice Kennedy Shriver National Institute of Child Health and Human Development

,

Ronald J. Wapner

⁷Department of Obstetrics and Gynecology, Columbia University, New York, New York

,

Dwight J. Rouse

⁸Department of Obstetrics and Gynecology, Brown University, Providence, Rhode Island

,

John M. Thorp

⁹Department of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

,

Edward K. Chien

¹⁰Department of Obstetrics and Gynecology, Case Western Reserve University-MetroHealth Medical Center, Cleveland, Ohio

,

George Saade

¹¹Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas

,

Alan M. Peaceman

¹²Department of Obstetrics and Gynecology, Northwestern University, Chicago, Illinois

,

Sean C. Blackwell

¹³Department of Obstetrics and Gynecology, University of Texas Health Science Center at Houston-Children's Memorial Hermann Hospital, Houston, Texas

,

for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network

› Author Affiliations

Abstract

Objective This study aimed to measure the association between hypertensive disorders of pregnancy (HDP) and long-term maternal metabolic and cardiovascular biomarkers.

Study Design Follow-up study of patients who completed glucose tolerance testing 5 to 10 years after enrollment in a mild gestational diabetes mellitus (GDM) treatment trial or concurrent non-GDM cohort. Maternal serum insulin concentrations and cardiovascular markers VCAM-1, VEGF, CD40L, GDF-15, and ST-2 were measured, and insulinogenic index (IGI, pancreatic β-cell function) and 1/ homeostatic model assessment (insulin resistance) were calculated. Biomarkers were compared by presence of HDP (gestational hypertension or preeclampsia) during pregnancy. Multivariable linear regression estimated the association of HDP with biomarkers, adjusting for GDM, baseline body mass index (BMI), and years since pregnancy.

Results Of 642 patients, 66 (10%) had HDP: 42 with gestational hypertension and 24 with preeclampsia. Patients with HDP had higher baseline and follow-up BMI, higher baseline blood pressure, and more chronic hypertension at follow-up. HDP was not associated with metabolic or cardiovascular biomarkers at follow-up. However, when HDP type was evaluated, patients with preeclampsia had lower GDF-15 levels (oxidative stress/cardiac ischemia), compared with patients without HDP (adjusted mean difference: −0.24, 95% confidence interval: −0.44, −0.03). There were no differences between gestational hypertension and no HDP.

Conclusion In this cohort, metabolic and cardiovascular biomarkers 5 to 10 years after pregnancies did not differ by HDP. Patients with preeclampsia may have less oxidative stress/cardiac ischemia postpartum; however, this may have been observed due to chance alone given multiple comparisons. Longitudinal studies are needed to define the impact of HDP during pregnancy and interventions postpartum.

Key Points

Hypertensive disorders of pregnancy were not associated with metabolic dysfunction.
Cardiovascular dysfunction was not consistently seen after pregnancy hypertension.
Longitudinal studies with postpartum interventions after preeclampsia are needed.

Keywords

cardiovascular - diabetes - hypertension - preeclampsia - pregnancy

Full Text

References

References
1 Heron M. Deaths: leading causes for 2019. Natl Vital Stat Rep 2021; 70 (09) 1-114
2 Lane-Cordova AD, Khan SS, Grobman WA, Greenland P, Shah SJ. Long-term cardiovascular risks associated with adverse pregnancy outcomes: JACC review topic of the week. J Am Coll Cardiol 2019; 73 (16) 2106-2116
3 Rice MM, Landon MB, Varner MW. et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Maternal-Fetal Medicine Units Network (MFMU). Pregnancy-associated hypertension in glucose-intolerant pregnancy and subsequent metabolic syndrome. Obstet Gynecol 2016; 127 (04) 771-779
4 Brown MC, Best KE, Pearce MS, Waugh J, Robson SC, Bell R. Cardiovascular disease risk in women with pre-eclampsia: systematic review and meta-analysis. Eur J Epidemiol 2013; 28 (01) 1-19
5 McDonald SD, Malinowski A, Zhou Q, Yusuf S, Devereaux PJ. Cardiovascular sequelae of preeclampsia/eclampsia: a systematic review and meta-analyses. Am Heart J 2008; 156 (05) 918-930
6 Lui NA, Jeyaram G, Henry A. Postpartum interventions to reduce long-term cardiovascular disease risk in women after hypertensive disorders of pregnancy: a systematic review. Front Cardiovasc Med 2019; 6: 160
7 Sheiner E, Kapur A, Retnakaran R. et al. FIGO (International Federation of Gynecology and Obstetrics) postpregnancy initiative: long-term maternal implications of pregnancy complications-follow-up considerations. Int J Gynaecol Obstet 2019; 147 (suppl 1): 1-31
8 Landon MB, Rice MM, Varner MW. et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (MFMU) Network. Mild gestational diabetes mellitus and long-term child health. Diabetes Care 2015; 38 (03) 445-452
9 Landon MB, Spong CY, Thom E. et al; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. A multicenter, randomized trial of treatment for mild gestational diabetes. N Engl J Med 2009; 361 (14) 1339-1348
10 Committee on Practice Bulletins. ACOG practice bulletin no. 190: gestational diabetes mellitus. Obstet Gynecol 2018; 131 (02) e49-e64
11 Committee on Practice Bulletins. ACOG practice bulletin no. 222: gestational hypertension and preeclampsia. Obstet Gynecol 2020; 135: e237-e260
12 Leung DN, Smith SC, To KF, Sahota DS, Baker PN. Increased placental apoptosis in pregnancies complicated by preeclampsia. Am J Obstet Gynecol 2001; 184 (06) 1249-1250
13 Levine RJ, Lam C, Qian C. et al; CPEP Study Group. Soluble endoglin and other circulating antiangiogenic factors in preeclampsia. N Engl J Med 2006; 355 (10) 992-1005
14 Sargent IL, Germain SJ, Sacks GP, Kumar S, Redman CWG. Trophoblast deportation and the maternal inflammatory response in pre-eclampsia. J Reprod Immunol 2003; 59 (02) 153-160
15 Nevo O, Soleymanlou N, Wu Y. et al. Increased expression of sFlt-1 in in vivo and in vitro models of human placental hypoxia is mediated by HIF-1. Am J Physiol Regul Integr Comp Physiol 2006; 291 (04) R1085-R1093
16 Chaiworapongsa T, Romero R, Kim YM. et al. Plasma soluble vascular endothelial growth factor receptor-1 concentration is elevated prior to the clinical diagnosis of pre-eclampsia. J Matern Fetal Neonatal Med 2005; 17 (01) 3-18
17 Ruma M, Boggess K, Moss K. et al. Maternal periodontal disease, systemic inflammation, and risk for preeclampsia. Am J Obstet Gynecol 2008; 198 (04) 389.e1-389.e5
18 Pontiroli AE, Pizzocri P, Caumo A, Perseghin G, Luzi L. Evaluation of insulin release and insulin sensitivity through oral glucose tolerance test: differences between NGT, IFG, IGT, and type 2 diabetes mellitus. A cross-sectional and follow-up study. Acta Diabetol 2004; 41 (02) 70-76
19 Wang J, Tan GJ, Han LN, Bai YY, He M, Liu HB. Novel biomarkers for cardiovascular risk prediction. J Geriatr Cardiol 2017; 14 (02) 135-150
20 Vasan RS. Biomarkers of cardiovascular disease: molecular basis and practical considerations. Circulation 2006; 113 (19) 2335-2362

Supplementary Material

Supplementary Material