650: sTRAIL, a prognostic marker for future death from cardiovascular disease, is decreased in maternal plasma of patients with preeclampsia

Abstract

650 sTRAIL, a prognostic marker for future death from cardiovascular disease, is decreased in maternal plasma of patients with preeclampsia Piya Chaemsaithong, Tinnakorn Chaiworapongsa, Tamara Stampalija, Nandor Gabor Than, Zhong Dong, Lami Yeo, Sonia Hassan, Roberto Romero NICHD/NIH/DHHS, Perinatology Research Branch, Detroit, MI, Wayne State University School of Medicine, Department of Obstetrics and Gynecology, Detroit, MI OBJECTIVE: Women who develop preeclampsia (PE) are at increased risk of cardiovascular disease later in life. Tumor necrosis factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL), a potent inducer of apoptosis, has anti-atherosclerotic effects on endothelial cells. Patients with acute coronary artery disease have lower serum concentrations of the soluble TRAIL (sTRAIL), with higher C-reactive protein (CRP) concentrations. sTRAIL and CRP confer a risk for future death (Hazard Ratio 0.93 and 2.2, respectively). The aim of this study was to determine if maternal plasma concentrations of sTRAIL and CRP change in pregnancies with preeclampsia. STUDY DESIGN: A cross-sectional study was conducted in the following groups: 1) normal pregnant women (n 93); and 2) women with PE (n 52). Patients with PE were sub-classified into preterm (n 38) and term ( 37 weeks) PE (n 14). Maternal plasma concentrations of sTRAIL and C-reactive protein (CRP) were determined by ELISA. RESULTS: 1) The median plasma concentration of sTRAIL was significantly lower in patients with PE than in normal pregnant women (25.6 pg/mL vs. 29.2 pg/mL; p 0.03); 2) the preterm (but not term) preeclampsia group had a significantly lower median plasma concentration of sTRAIL than the normal pregnancy group (24.8 pg/mL vs. 30.5 pg/mL; p 0.03 and 26.5 pg/mL vs. 26.8 pg/mL; p 0.7, respectively); and 3) the median plasma concentration of CRP was significantly higher in patients with PE (n 32) than in normal pregnant women (n 53) (8 ng/mL vs. 4.1 ng/mL; p 0.001); however, there was no significant correlation between maternal plasma concentrations of sTRAIL and CRP in either PE (p 0.1) or normal pregnancy (p 0.3). CONCLUSION: Preeclampsia was associated with a lower sTRAIL and a higher CRP concentration in maternal plasma. Both proteins may be involved in the mechanisms of predisposing patients with preeclampsia to future cardiovascular disease. 651 Prospective evaluation of circulating angiogenic factors in the prediction of earlyversus late-onset pre-eclampsia Rebecca Jessel, Ann Thomas, Kee-Hak Lim, Samuel Parry, Thomas McElrath Brigham and Women’s Hospital; Harvard Medical School, Department of Obstetrics and Gynecology, Boston, MA, Brigham and Women’s Hospital; Harvard Medical School, Department of Obstetrics and Gynecology; Division of Maternal Fetal Medicine, Boston, MA, Boston MFM; BIDMC; Harvard Medical School, Boston Maternal-Fetal Medicine, Boston, MA, Hospital of the University of Pennsylvania, Division of Maternal-Fetal Medicine, Hospital of the University of Pennsylvania, PA OBJECTIVE: Circulating angiogenic factors play a role in pathogenesis of preeclampsia (PE) but we have previously demonstrated that they have limited predictive capacity if PE is considered a single entity. However, PE is a heterogeneous disease with early ( 34w) and late onest PE possibly representing different entities. We tested the hypothesis that sequential measurement of sFlt-1 and PlGF in a longitudinal cohort of patients can distinguish patients who are more likely to develop and require delivery for early PE. STUDY DESIGN: 2,241 singleton pregnancies were followed prospectively from the initiation of prenatal care at three regional academic centers. Plasma sFlt-1 and PlGF levels were collected prospectively and quantified by immunoassay at approximately 10, 17, and 24 weeks gestation. Patients were followed through delivery. PE was diagnosed by ACOG criteria. Patients with chronic hypertension and diabetes were excluded from this analysis. RESULTS: Median analyte concentrations for early and late and testing characteristics for the prediction of early PE are presented in the table. Twenty patients developed PE before 34 weeks compared to 182 patients with late PE. Incidence of early PE was 1%. PlGF concentrations are significantly lower among early PE patients at all time points and magnitude of increase with gestation was lower than those with late PE. sFlt-1 concentrations and the ratio are significantly different at 26 weeks. However, the testing characteristics do not suggest clinical utility in the prediction of early PE. CONCLUSION: Our results support the suggestion that PE is a heterogeneous disease with early and late PE possibly representing different disease processes. Despite low incidence, the significant differences in analytes in early versus late suggests a more homogenous cohort. However, the analytes, do not appear to be clinically useful in the prediction of early PE.