A longitudinal analysis of angiotensin II type 1 receptor antibody and angiogenic markers in pregnancy

Abstract

Background: Preeclampsia can be caused by shallow trophoblast invasion and results in endothelial dysfunction. Angiotensin II type 1 receptor antibodies may have a role in both processes. Other angiogenic markers (placental growth factor, soluble fms-like tyrosine kinase-1, and soluble endoglin) have been shown to alter before clinically evident preeclampsia.

Objective: The aim of this study is to assess the longitudinal changes and utility of biomarker angiotensin II type 1 receptor antibodies and angiogenic markers in hypertensive disorders of pregnancy, gestational hypertension, and preeclampsia.

Study design: A longitudinal prospective cohort observational study of angiogenic markers and a secondary retrospective case-control study of angiotensin II type 1 receptor antibody changes were conducted. The studies were conducted in a large tertiary metropolitan teaching hospital (Sydney, Australia). Sequential recruitment of women with a singleton pregnancy (N = 351) was undertaken. Plasma concentrations of angiotensin II type 1 receptor antibodies, placental growth factor, soluble fms-like tyrosine kinase-1, and soluble endoglin were measured using validated enzyme-linked immunosorbent assays at 12, 18, 28, 36, and 40 weeks' gestation and 6 weeks' postpartum. Clinical, demographic, and pregnancy data were prospectively collected. Pregnancy outcomes were classified as normotensive, gestational hypertension, or preeclampsia. Analyses were carried out using software and significance set at P < .05.

Results: In all, 351 women were recruited, 17 developed gestational hypertension, and 18 developed preeclampsia. Women with preeclampsia at baseline were heavier (P = .015), were taller (P = .046), and had higher systolic (P = .029) and diastolic (P = .006) blood pressure. The preeclampsia group had higher soluble fms-like tyrosine kinase-1 from ≥28 weeks (P = .003) and lower placental growth factor from 18 weeks (P = .004). Soluble endoglin and angiotensin II type 1 receptor antibodies did not vary over time or between groups. Angiotensin II type 1 receptor antibody (12 weeks) was positively correlated with serum pregnancy associated plasma protein A (P = .008) and human chorionic gonadotrophin (P = .04).

Conclusion: Angiogenic markers vary longitudinally during pregnancy and placental growth factor and soluble fms-like tyrosine kinase-1 have a role for predicting and diagnosing preeclampsia later in disease. Our data show that angiotensin II type 1 receptor antibodies are not sensitive for disease and hence not useful as a biomarker. Larger studies are required to describe the role and functionality of angiotensin II type 1 receptor antibodies in preeclampsia.

Keywords: angiotensin II type 1 receptor antibodies; placental growth factor; preeclampsia; soluble endoglin; soluble fms-like tyrosine kinase 1.