Chronic hypertension in pregnancy: the impact of ethnicity and superimposed preeclampsia on placental, endothelial and renal biomarkers

Black ethnicity is associated with worse pregnancy outcomes in women with chronic hypertension. Pre-existing endothelial and renal dysfunction, and poor placentation may contribute but pathophysiological mechanisms underpinning increased risk are poorly understood. This cohort study aimed to investigate the relationship between ethnicity, superimposed pre-eclampsia and longitudinal changes in markers of endothelial, renal and placental dysfunction in women with chronic hypertension. Plasma concentrations of placental growth factor (PlGF), syndecan-1, renin, aldosterone, and urinary angiotensinogen:creatinine ratio (AGTCR), protein:creatinine ratio (PCR) and albumin:creatinine ratio (ACR) were quantified during pregnancy and postpartum in women with chronic hypertension. Comparisons of longitudinal biomarker concentrations were made using log-transformation and random effects logistic regression allowing for gestation. Of 117 women, superimposed preeclampsia was diagnosed in 21% (n=25), with 24% (n=6) having an additional diagnosis of diabetes. The cohort included 63 (54%) women who self-identified as of Black ethnicity. PlGF concentrations were 67% lower (95% CI -79% to -48%), and AGTCR, PCR and ACR were higher over gestation, in women with subsequent superimposed preeclampsia (compared to those without superimposed preeclampsia). PlGF <100 pg/mL at 20-23.9 weeks' gestation predicted subsequent birthweight <3rd centile with 88% sensitivity (95% CI 47%-100%) and 83% specificity (95% CI 70%-92%). Black women had 43% lower renin (95% CI -58% to -23%) and 41% lower aldosterone (95%CI -45% to -15%) concentrations over gestation. Changes in placental (PlGF) and renal (AGTCR/PCR/ACR) biomarkers predated adverse pregnancy outcome. Ethnic variation in the renin-angiotensin-aldosterone system exists in women with chronic hypertension in pregnancy and may be important in treatment selection.