Serum Beta-trace Protein As A Novel Predictor Of Pregnancy-induced Hypertension

Background:Pregnancy-induced hypertension(PIH)is one of the commonest medical problems during pregnancy,and is the main cause of pregnant women and fetal morbidity and mortality.The treatment of pregnancy-induced hypertension depends on many factors,including blood pressure levels,gestational age,the presence of symptoms and related risk factors.Hypertensive pregnant women have an increased risk of later cardiovascular disease and mortality.Compared with normal pregnant women,pregnancy hypertension syndrome have a higher placental abruption,cerebrovascular,organ failure and the risk of disseminated intravascular coagulation.While these fetal of gestational hypertension mother has higher risk related symptoms,such as fetal developmental delays,preterm birth and intrauterine fetal death.Early diagnosis,closely antenatal surveillance,and timely intervention are the key to the management of pregnancy-induced hypertension.So far,there are no reliable,economic,and reproducible screening tests that are available.Pregnancy-induced hypertension have been characterized by insulin resistance,sympathetic over-activity and exaggerated systemic inflammation,which were all features characteristic for metabolic syndrome.Sex hormone binding globulin(SHBG)and insulin resistance are closely to hyperinsulinernia,SHBG reduction result in higher free testosterone index,androgen can strengthen blood vessel reactivity of vascular active substances,reduce the top ring element levels and increase production of thromboxane,directly increase the platelet aggregation induced by micro thrombosis,moreover,inflammatory disease in pih play an important role in the process,because of the symptoms of chronic vasculitis in placenta of PIH pregnant women increased significantly.Existing studies have shown that the serum testosterone,sex hormone binding globulin(SHBG),hypersensitive c-reactive protein level is associated with hypertension during pregnancy,the purpose of this subject is from the pregnancy-induced hypertension syndrome patients special performance to find more effective to evaluate the high risk factor of pregnancy-induced hypertension syndrome and potential biomarkers of molecules.Beta-trace protein(BTP),also known as prostaglandin D2 synthase,is a protein belonging to the lipocalin protein family.Recent traces for beta protein research mainly focus on it as a serum creatinine alternative markers used for evaluation of renal function,as well as a new marker of cardiovascular disease.Beta trace protein can be used as ideal marker of diabetes caused abnormal renal function.Although the opposite results.Research has showed that beta trace proteins related to many biological processes,including inflammation,angina pectoris,atherogenesis,vasomotor reaction and systemic arterial pressure.Beta trace protein significantly gathered in the pathological changes of coronary atherosclerotic stenosis of fibrous plaques.There are multiple research reports,the levels of serum beta trace protein is significantly higher in patients with coronary heart disease(CHD)for a long time,and the rise of serum beta trace protein level is closely related to the number of damaged blood vessels,age and hypertension.High levels of beta trace protein levels can predict atrial fibrillation patients receiving anticoagulation adverse cardiovascular events and mortality and the occurrence of major bleeding.These findings suggest that beta trace protein levels may can be used in the reaction process of the onset of cardiovascular disease.Hirawa comparison beta trace protein level between the normal and patients with high blood pressure,he found that of hypertension patient was significantly higher than that of normal control group.Different studies have revealed the role of beta-trace protein(BTP)in hypertension.However,the role of circulating beta-trace protein(BTP)in the pathogenesis of pregnancy-induced hypertension is still incompletely understood.Thus,the aim of this study was to evaluate serum beta-trace protein levels in normal pregnancy and patients with pregnancy-induced hypertension.To the best of our knowledge,this is the first study demonstrating the relationship between presence of pregnancy-induced hypertension and beta-trace protein levels.Objective:By comparing the normal pregnant women and patients with pregnancy-induced hypertension group of age,pre-pregnancy BMI,pregnancy history,blood pressure,body weight,left ventricular ejection fraction(LVET),c-reactive protein(hs-CRP),testosterone,sex hormone binding globulin(SHBG)and beta trace protein(BTP).The aim of this study was to study gestational hypertension risk factors of pregnant women and whether serum testosterone,sex hormone binding globulin(SHBG),hypersensitive c-reactive protein levels associated with gestational hypertension.Determine the concentration of serum beta-trace protein(BTP)in healthy pregnant women and patients with pregnancy-induced hypertension.To assess the level of serum trace beta protein(BTP)as the new more effective prediction markers of pregnancy induced hypertension syndrome and its recognition ability to the diagnosis of pregnancy-induced hypertension syndrome.Methods:1206 pregnant women attended the outpatient facilities at QiLu Hospital of Shandong University and Central Hospital of Zibo(2014).Among them,57 normotensive pregnancies(control group:normotensive women had normal BP<140/90 mmHg and no proteinuria during pregnancy),46 pregnant women who developed pregnancy-induced hypertension(PIH group):defined as systolic BP(SBP)elevation to ≥140 mmHg or diastolic BP(DBP)elevation to>90 mmHg after 20 weeks of gestation with preeclampsia or without proteinuria,on two occasions,at least 4 h apart during pregnancy,with no hypertension before 20 gestational weeks)enrolled in this study.46 pregnancy-induced hypertension by the presence of proteinuria is divided into pure hypertension group and preeclampsia.According to left ventricular ejection fraction of 60%is bounded into LVEF<60%group and a LVET 60%or more in the two groups.All cases were uncomplicated singleton pregnancies.The pregnancy-induced hypertension and control groups were matched for gestational age and maternal age.Exclusion criteria include:gestational hypertension group may also accompany with other diseases,such as the second type of hypertension,coronary heart disease,kidney disease,or diabetes,etc.First collect clinical indicators of all pregnant women,such as maternal average age(years old),pre-pregnancy BMI(kg/m2),anemia(n%),Asian race(n%),family history of PIH(n%),history of spontaneous abortion(>3)(n%),the number of pregnancy(>3)(n%),and comparative analysis of the systolic blood pressure(MMHG),diastolic blood pressure(MMHG),gestational age at birth(days),childbirth way,(n,%),normal vaginal delivery,CS,and neonatal placenta weight(g),gender(n%)and birth weight newborn(g),and other data.In the middle-late pregnancy ultrasound cardiogram monitoring left ventricular ejection fraction(LVET).Blood samples were collected during the first trimester(1-12 gestational weeks),second trimester(13-27 gestational weeks),and third trimester(28-40 gestational weeks)with the informed consent of each woman.A double-blind procedure is used in this study.Venous blood samples of PIH group and control group were drawn into heparinized(serum)tubes on ice,centrifuged at 4℃ and 7,000 rpmfor 10 min.The samples were stored at-80℃ until analysis.Enzyme-linked immunoassay analysis method to determine serum SHBG concentration,immune luminescence method determination of testosterone and hypersensitive c-reactive protein levels.The levels of serum protein beta trace using enzyme-linked immunosorbent(ELISA)kits for testing.Hs-CRP(mg/1)(mid pregnancy and late pregnancy),testosterone(mid pregnancy and late pregnancy),SHBG(nmol/1)(mid pregnancy and late pregnancy)data and BTP.ELISA test results using nonparametric tests.The potential risk assessment by ROC curve drawing were analyzed.Results:(1)Women with pregnancy-induced hypertension had a higher pre-pregnancy BMI(p<0.05),greater incidence of anemia(p<0.001),and higher incidence of a family history of PIH(p<0.001)compared to gestational age and maternal age matched controls;(2)Through the contrast analysis of pregnant women serum testosterone,c-reactive protein(hs-CRP)and the level of sex hormone binding globulin(SHBG)tip in gestational hypertension group and normal pregnancy group differences had no statistical significance;(3)Serum beta-trace protein levels in normal pregnancy did not change significantly.Moreover,no significant difference was detected in the serum concentration of beta-trace protein in normal pregnant women based on the maternal age and body mass index(BMI).However,serum beta-trace protein levels at the second and third trimesters in pregnancy-induced hypertension groups were significantly higher than those in normal control groups.While,there was no significant difference in pregnancy-induced hypertension groups between the second trimester and third trimester;(4)Moreover,comparing women with pregnancy induced hypertension to normal pregnancy,no significant difference was found in beta-trace protein levels at the first trimester;(5)Preeclampsia group to be associated with the level of serum trace beta protein higher than pure hypertension group,statistically significant difference;(6)The potential value of serum beta-trace protein in the determination of pregnancy-induced hypertension was analyzed using receiver operating characteristic(ROC)analysis.The result of receiver operating characteristic analysis revealed that using serum beta-trace protein 321.3 ng/mL as a cutoff value,the sensitivity was 91.3%and the specificity was 89.5%.Conclusion:1.Pregnant women with gestational hypertension family history,higher pre-pregnancy BMI,anemia during pregnancy should be incorporated into the gestational hypertension risk monitoring the crowd.2.Studies have reported the serum testosterone,c-reactive protein(hs-CRP),the level of sex hormone binding globulin(SHBG)associated with hypertension during pregnancy,and the correlation are not found in this study.3.Pregnant women with pregnancy-induced hypertension,serum beta trace protein levels with different stages of pregnancy appear gradually rising trend.Compared with normal pregnant women,pregnant women with gestational hypertension the levels of serum beta trace protein during the mid and late pregnancy pregnant women is significantly higher than normal control group.Preeclampsia group than simple hypertension group the levels of serum trace beta protein increased significantly.Left ventricular ejection fraction of less than 60%of pregnant women serum protein beta trace levels increased significantly,the above results suggest a high level of serum beta trace protein with gestational hypertension has certain connection,which can be used to reflect the disease process of pregnancy-induced hypertension syndrome,in addition,the serum protein beta trace as a PIH affects the predictors of kidney or cardiac function,and with other studies have found that B-trace protein can be used as the markers consistent conclusion,heart kidney function abnormal pregnant women can be used in the reaction of pregnancy hypertension syndrome of disease severity.4.By ROC analysis showed that beta trace protein levels used for prediction of pregnancy-induced hypertension syndrome with high sensitivity and specificity,therefore,the level of serum protein beta trace is expected to become new Asian populations of pregnancy-induced hypertension syndrome diagnostic markers,in pregnant women with high-risk factors for testing prediction can be improved sensitivity,used for prediction of gestational hypertension.