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

Abstract

Black ethnicity is associated with worse pregnancy outcomes in women with chronic hypertension. Preexisting 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 preeclampsia, 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, and aldosterone and urinary angiotensinogen-to-creatinine ratio (AGTCR), protein-to-creatinine ratio (PCR), and albumin-to-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 being of black ethnicity. PlGF concentrations were 67% lower [95% confidence interval (CI) -79 to -48%] and AGTCR, PCR, and ACR were higher over gestation, in women with subsequent superimposed preeclampsia (compared with those without superimposed preeclampsia). PlGF <100 pg/ml at 20-23.9 wk of gestation predicted subsequent birth weight <3rd percentile 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.

A systematic review and meta-analysis indicates long-term risk of chronic and end-stage kidney disease after preeclampsia

“…As a consequence, follow-up after a PE episode is not established. [1][2][3][4][13][14][15][16][17][18][19][20][21][22][23][31][32][33][34][35][36][37][38][39][40][41] There are several reasons why the results of the analyses of these long-term health effects are not fully clear: the pathogenesis of PE is only partially understood; the recent trend Delivery before the 34th wk of gestation, blood pressure >140/90 mm Hg, and proteinuria >300 mg/24 h. f Diastolic blood pressure $90 mm Hg with proteinuria ($0.3 g/24 h) diagnosed between the 20th and 32nd wk of gestation. g Diastolic pressure >90 mm Hg on 2 occasions at least 4 h apart or a single reading of >110 mm Hg; from the 20th wk of gestation onward in a previously normotensive woman plus at least 1 episode of proteinuria of 0.3 g/24 h. Increased BP after the 20th wk of gestation (>140/90 mm Hg) and proteinuria (>0.3 g in a 24-h urine specimen or $1þ on a urinary dipstick reading).…”

“…[1][2][3][4][18][19][20][21][22][23] The discussion on whether PE is a single disease, a syndrome, or a spectrum of alterations is still open; the new molecular approaches, and in particular the analysis of the ratio between proangiogenic and anti-angiogenic factors, such as placental growth factor and soluble fms-like tyrosine kinase 1, may offer some interesting insights into its pathogenesis. [1][2][3][4][21][22][23][24][25][26][27][28][29][30] PE is no longer considered as a transitory disease and has been associated with a vast array of cardiovascular and renal diseases, of which the pregnancy-related affection may be a herald, a cause, or a consequence. [31][32][33][34][35][36] Most of the studies and virtually all the systematic reviews show that patients who had PE in $1 pregnancy are at an increased risk of developing cardiovascular and metabolic diseases.…”

Maternal Sildenafil vs Placebo in Pregnant Women With Severe Early-Onset Fetal Growth Restriction

“…Maternal race/ethnicity was collected because maternal race/ethnicity is associated with placental dysfunction and pregnancy outcomes. 18,19 Whether the maternal race/ethnicity was European descent, African descent, or Asian descent was indicated by the investigator. In case of doubt, the patient was asked to report her race/ethnicity.…”

Prevention = Pre-Conception Counselling

“…Women with pre-existing hypertension or cardiac disease, a history of significant obstetrical-induced hypertension, or a history of fetal or neonatal congenital heart disease require important pre-conception counselling related to the maternal and fetal risks in a subsequent pregnancy (Table 1). [1][2][3][4][5][6][7][8] Clapp and Bernstein summarize the pre-conception counselling approach for women with cardiac disease that uses risk stratification and pre-pregnancy optimization (workup, medication exposures, genetics). 1 According to the Public Health Agency of Canada, 9 6% of pregnancies are complicated by hypertension, roughly evenly split between chronic hypertension and gestational hypertension or preeclampsia.…”