Estudio del efecto del tratamiento con pravastatina sobre la función endotelial vascular en mujeres con alto riesgo de preeclampsia tardía

Resum

BACKGROUND: Preeclampsia is an important cause of maternal and neonatal morbidity and mortality. It begins in the placenta, but its target organ is the maternal endothelium, which is affected by generalized dysfunction. Preeclampsia shares pathophysiological mechanisms with cardiovascular disease which has led to research into the potential of statins in its management and prevention. Statins have pleiotropic properties that exert a protective effect on the endothelium. Endothelial function can be assessed through circulating biomarkers that allow the study of mechanisms of endothelial pathology, to obtain information on the status of the endothelium, so they can be effective in studying the effect of statins on endothelium. HYPOTHESIS: Pravastatin treatment in pregnancies at high risk of term preeclampsia improves vascular endothelial function associated with a decrease in oxidative stress, inflammation, and release of maternal vascular and syncytiotrophoblast circulating microvesicles. OBJECTIVES: To compare the level of oxidative stress, inflammatory status, endothelial function, and lipid profile in pregnant women at low and high risk of term preeclampsia. To analyze the performance of circulating biomarkers, their dependence relationships, and their correlation with demographic and clinical variables in pregnant women at low and high risk of term preeclampsia. To develop an explicative model of the risk of term preeclampsia based on circulating biomarkers of vascular endothelial function. To study the effect of pravastatin use on vascular endothelial function. METHODOLOGY: We carried out a prospective, descriptive, and analytical study of the effect of 20 mg daily of pravastatin on vascular endothelial function in 68 pregnant women at high risk of term preeclampsia enrolled in a clinical trial (ISRCTN16123934). To complete the proposed objectives, 57 pregnant women of the same gestational age with low risk of term preeclampsia were recruited. In all cases clinical data were collected and concentrations of circulating biomarkers of oxidative stress, inflammation, endothelial function, and lipid profile were measured. CONCLUSIONS: Pregnancies at high risk of term preeclampsia show signs of vascular endothelial dysfunction determined by observed changes in circulating biomarkers of oxidative stress (serum total antioxidant capacity, homocysteine, and uric acid), inflammation (Interleukin 6 and growth differentiation factor 15), and endothelial function (extracellular microvesicles and asymmetric dimethyl arginine). The combination of biomarkers which best explains the risk of term preeclampsia includes homocysteine, Interleukin 6 and leukocyte and placental microvesicles levels, demonstrating that oxidative stress, inflammation and endothelial dysfunction are characteristic of pregnancies at high risk of term preeclampsia. The dependence relationship of blood pressure with uric acid, homocysteine, and leukocyte microvesicles levels suggests that the higher mean arterial pressure values observed in women at high risk for term preeclampsia may be because of an alteration in endothelial function. The administration of 20 mg of pravastatin daily to pregnant women at high risk of term preeclampsia reduces the concentration of microvesicles derived from the placenta and the maternal vascular system, and improves the lipid profile, demonstrating its potential beneficial effect on the vascular endothelium. The pattern of alteration of different biomarkers of oxidative stress, inflammation, and endothelial dysfunction in pregnancies at high risk of term preeclampsia is like that observed in cardiovascular disease, suggesting that these women may have an additional increased risk of developing long-term adverse cardiovascular events.