First trimester inflammatory mediators in women with chronic hypertension.

INTRODUCTION: Chronic hypertension complicates 1%-2% of pregnancies and is one of the most significant risk factors for the development of preeclampsia. Inflammatory mediators, such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), vascular cell adhesion molecule (VCAM) and endothelin have been implicated in the endothelial dysfunction that is pathognomonic of preeclampsia and may serve as useful first trimester biomarkers for the prediction of preeclampsia. The objectives of this study are: first, to investigate differences in serum levels of IL-6, TNF-α, VCAM and endothelin at 11+0 to 13+6 weeks' gestation in women with chronic hypertension who developed superimposed preeclampsia with those who did not and normotensive controls and, second, to evaluate the performance of these biomarkers in the prediction of preeclampsia. MATERIAL AND METHODS: The study population was comprised of 650 women with chronic hypertension, including 202 who developed superimposed preeclampsia and 448 who did not, and 142 normotensive controls matched to the chronic hypertension group for storage time and racial origin. Serum concentrations of IL-6, TNF-α, VCAM and endothelin were measured and the values were converted into multiples of the expected median using multivariate regression analysis in the control group. The multiples of the median values of the biomarkers between the two groups of women with chronic hypertension and the controls were compared, and the receiver operating characteristic curve (ROC) was used to assess the performance of these variables for the prediction of preeclampsia. RESULTS: In women with chronic hypertension, compared with the normotensive controls, there was a significantly higher first trimester median concentration of endothelin but not of VCAM, IL-6 or TNF-α. Within the cohort of women with chronic hypertension, those who developed superimposed preeclampsia, compared with those who did not, had higher first trimester serum concentration of VCAM but not of endothelin, IL-6 or TNF-α. However, serum VCAM provided a poor prediction of superimposed preeclampsia (area under the ROC curve 0.537, 95% CI 0.487-0.587). CONCLUSIONS: Women with chronic hypertension have increased serum endothelin in the first trimester of pregnancy and those who develop superimposed preeclampsia have higher levels of VCAM. None of the inflammatory mediators performed well in the first trimester in the prediction of preeclampsia.

First trimester serum angiogenic and anti-angiogenic factors in women with chronic hypertension for the prediction of preeclampsia.

BACKGROUND: An imbalance between angiogenic and antiangiogenic factors is thought to be a central pathogenetic mechanism in preeclampsia. In pregnancies that subsequently experience preeclampsia, the maternal serum concentration of the angiogenic placental growth factor is decreased from as early as the first trimester of pregnancy, and the concentration of the antiangiogenic soluble fms-like tyrosine kinase-1 is increased in the last few weeks before the clinical presentation of the disease. Chronic hypertension, which complicates 1-2% of pregnancies, is the highest risk factor for the development of preeclampsia among all other factors in maternal demographic characteristics and medical history. Two previous studies in women with chronic hypertension reported that first-trimester serum placental growth factor and soluble fms-like tyrosine kinase-1 levels were not significantly different between those who experienced superimposed preeclampsia and those who did not, whereas a third study reported that concentrations of placental growth factor were decreased. OBJECTIVE: The purpose of this study was to investigate whether, in women with chronic hypertension, serum concentrations of placental growth factor and soluble fms-like tyrosine kinase-1 and soluble fms-like tyrosine kinase-1/placental growth factor ratio at 11+0-13+6 weeks gestation are different between those women who experienced superimposed preeclampsia and those who did not and to compare these values with those in normotensive control subjects. STUDY DESIGN: The study population comprised 650 women with chronic hypertension, which included 202 women who experienced superimposed preeclampsia and 448 women who did not experience preeclampsia, and 142 normotensive control subjects. Maternal serum concentration of placental growth factor and soluble fms-like tyrosine kinase-1 were measured by an automated biochemical analyzer and converted into multiples of the expected median with the use of multivariate regression analysis in the control group. Comparisons of placental growth factor and soluble fms-like tyrosine kinase-1 levels and soluble fms-like tyrosine kinase-1/placental growth factor ratio in multiples of the expected median values between the 2 groups of chronic hypertension and the control subjects were made with the analysis of variance or the Kruskal-Wallis test. RESULTS: In the group of women with chronic hypertension who experienced preeclampsia compared with those women who did not experience preeclampsia, there were significantly lower median concentrations of serum placental growth factor multiples of the expected median (0.904 [interquartile range, 0.771-1.052] vs 0.948 [interquartile range, 0.814-1.093]; P=.014) and soluble fms-like tyrosine kinase-1 multiples of the expected median (0.895 [interquartile range, 0.760-1.033] vs 0.938 [interquartile range, 0.807-1.095]; P=.013); they were both lower than in the normotensive control subjects (1.009 [interquartile range, 0.901-1.111] and 0.991 [interquartile range, 0.861-1.159], respectively; P<.01 for both). There were no significant differences among the 3 groups in soluble fms-like tyrosine kinase-1/placental growth factor ratios. In women with chronic hypertension, serum placental growth factor and soluble fms-like tyrosine kinase-1 levels provided poor prediction of superimposed preeclampsia (area under the curve, 0.567 [95% confidence interval, 0.537-0.615] and 0.546 [95% confidence interval, 0.507-0.585], respectively). CONCLUSION: Women with chronic hypertension, and particularly those who subsequently experienced preeclampsia, have reduced first-trimester concentrations of both placental growth factor and soluble fms-like tyrosine kinase-1.