Predictive Value of Multiple Indicators such as Pregnancy-Associated Plasma Protein A in Early Pregnancy for Gestational Diabetes Mellitus / 实用妇产科杂志

Objective:To investigate the predictive value of pregnancy-associated plasma protein A(PAPP-A),fasting blood glucose(FPG),body mass index(BMI)and age in gestational diabetes mellitus(GDM)during the first trimester.Methods:A retrospective analysis was performed on 792 pregnant women who underwent pre-natal examination and delivered in Sichuan Provincial Maternal and Child Health Care Hospital from December 2021 to June 2022.They were divided into GDM group(232 cases)and control group(560 cases)according to whether they had GDM.The clinical data,serum PAPP-A median multiple(PAPP-A MoM)in early pregnancy and FPG levels were compared between the two groups.The indicators with statistical significance in univariate analy-sis were included in multivariate Logistic regression analysis to analyze the related factors affecting the occurrence of GDM.The receiver operating curve(ROC)and area under the curve(AUC)of different indexes were plotted to compare the efficacy of GDM prediction.Results:①The age,pre pregnancy BMI,early pregnancy FPG and the proportion of assisted reproductive technology in GDM group were higher than those in control group,and the differences were statistically significant(P＜0.05).The early pregnancy PAPP-A MoM level in GDM group was lower than that in control group,and the difference was statistically significant(P＜0.05).②Multivariate Logistic regression analysis showed that older age,lager pre-pregnancy BMI and lager FPG in the first trimester were in-dependent risk factors for GDM occurrence(OR＞1,P＜0.05),while an increase of PAPP-A MoM in the first tri-mester was a protective factor(OR＜1,P＜0.05).③ROC showed that the combination of PAPP-A MoM in early pregnancy,FPG in early pregnancy,BMI in pre-pregnancy and age had the highest AUC(0.752)when predicting GDM,with a sensitivity of 55.6％and a specificity of 84.3％.Conclusions:The combined screening of serologi-cal(PAPP-A +FPG)and clinical data(pre-pregnancy BMI +age)in early pregnancy has a high clinical application prospect and can be popularized.

Effect of subchorionic hematoma on first-trimester maternal serum free β-hCG and PAPP-A levels

Abstract Objective This study aimed to investigate the effects of the presence of subchorionic hematoma (SH) in early pregnancies with threatened miscarriage (TM) on levels of first-trimester maternal serum markers, pregnancy-associated plasma protein-A (PAPP-A), and free β-human chorionic gonadotropin (β-hCG) levels. Methods The data of TM cases with SH in the first trimester between 2015 and 2021 were evaluated retrospectively. The data of age and gestational age-matched TM cases without SH were also assessed to constitute a control group. Demographic characteristics, obstetric histories, ultrasonographic findings, and free β-hCG and PAPP-A levels of the groups were compared. Results There were 119 cases in the study group and 153 cases in the control group. The median vertical and longitudinal lengths of the SH were 31 mm and 16 mm. The median age of both groups was similar (p=0.422). The MoM value of PAPP-A was 0.088 (.93) in the study group and 0.9 (0.63) in the control group (p=0.519). Similarly, the MoM value of free β-hCG was 1.04 (0.78) in the study group and 0.99 (0.86) in the control group (p=0.66). No significant relationship was found in the multivariate analysis between free β-hCG MoM, PAPP-A MoM, age, gravida, and vertical and longitudinal lengths of the hematoma (p>0.05). Conclusion The level of PAPP-A and free β-hCG were not affected by the SH. Therefore, these markers can be used reliably in TM cases with SH for the first-trimester fetal aneuploidy screening test.

Validación de la calculadora de la Fundación de Medicina Fetal para tamiz de preeclampsia adaptada a población mexicana / Validation of the Fetal Medicine Foundation calculator for pre-eclampsia screening test adapted to a Mexican population

Resumen OBJETIVO: Validar el rendimiento de la calculadora de la Fundación de Medicina Fetal 4.0 adaptada a población mexicana. MATERIALES Y MÉTODOS: Estudio de cohorte efectuado en embarazos con feto único, según el modelo de riesgos en competencia para preeclampsia en un centro de medicina fetal de la Ciudad de México. El riesgo a priori se calculó de acuerdo con la historia clínica. La presión arterial media, el índice de pulsatilidad medio de la arteria uterina y la proteína plasmática A asociada al embarazo se midieron a las 11 a 14 semanas de gestación con metodología estandarizada. El valor de cada marcador se transformó en múltiplos de la mediana adaptados a la población local. Se aplicaron la distribución normal multivariante y el teorema de Bayes para obtener las probabilidades posprueba individuales, que se utilizaron como clasificadores para el área bajo la curva de característica receptor-operador. RESULTADOS: La incidencia de preeclampsia fue del 5.0% (54/1078). El área bajo la curva de característica receptor-operador fue de 0.784 (0.712; 0.856) para preeclampsia a menos de 37 semanas y de 0.807 (0.762; 0.852) para preeclampsia global. CONCLUSIONES: La calculadora FMF 4.0 adaptada a población mexicana resultó válida. Si bien tuvo menor rendimiento al esperado para preeclampsia a menos de 37 semanas, el rendimiento para preeclampsia global fue satisfactorio. Se justifica desarrollar la calculadora local.

Abstract OBJECTIVE: To validate the performance of the Fetal Medicine Foundation 4.0 calculator adapted to the Mexican population. MATERIALS AND METHODS: Cohort study performed in singleton pregnancies, according to the competing risk model for preeclampsia in a fetal medicine center in Mexico City. The a priori risk was calculated according to the clinical history. Mean arterial pressure, mean uterine artery pulsatility index and pregnancy-associated plasma protein A were measured at 11 to 14 weeks of gestation with standardized methodology. The value of each marker was transformed into multiples of the median adapted to the local population. Multivariate normal distribution and Bayes' theorem were applied to obtain individual posttest probabilities, which were used as classifiers for the area under the receiver-operator characteristic curve. RESULTS: The incidence of preeclampsia was 5.0% (54/1078). The area under the receiver-operator characteristic curve was 0.784 (0.712; 0.856) for preeclampsia at less than 37 weeks and 0.807 (0.762; 0.852) for global preeclampsia. CONCLUSIONS: The FMF 4.0 calculator adapted to Mexican population proved valid. Although it had lower performance than expected for preeclampsia at less than 37 weeks, the performance for global preeclampsia was satisfactory. The development of the local calculator is justified.

Effect of first trimester maternal serum pregnancy associated plasma protein: a level on fetomaternal outcome

Background: Serum pregnancy-associated plasma protein-A (PAPP-A) levels fluctuate in continuation with the pregnancy and thus become an important standalone marker in monitoring the adverse outcomes that may occur in pregnancy.Methods: A prospective observational study was conducted in the department of obstetrics and gynaecology. A total of 240 pregnant women in their first trimester were included in the study. Serum PAPP-A levels were measured at 11-13+6week of gestation and were evaluated with respect to the feto-maternal outcome. The data was entered in MS excel spreadsheet and analysis was done using Statistical Package for Social Sciences (SPSS) version 21.0.Results: The mean age of the study population was 27 years. Among the maternal pregnancy parameters, PIH, pre-term labor and Emergency LSCS were significantly associated with low (<0.5 MoM) Serum PAPP-A levels, P<0.05. All the fetal outcome measures: IUGR, IUD, low birth weight, SGA babies, prematurity and NICU admissions, were significantly associated with low (<0.5 MoM) Serum PAPP-A levels, p <0.05.Conclusions: Serum PAPP-A in the early pregnancy showed significant correlation with feto-maternal outcome. Thus, it has the potential to be used as a prognostic factor and in the management of adverse outcomes by increasing surveillance for pregnant women with high-risk factors.

Corrección de los múltiplos de la mediana de los biomarcadores del modelo de predicción de preeclampsia de la Fetal Medicine Foundation para población mexicana / Correction of the multiples of median of the biomarkers used in the Fetal Medicine Foundation's prediction model for preeclampsia in Mexican population

Resumen OBJETIVO: Calcular y ajustar los múltiplos de la mediana para el índice de pulsatilidad medio de las arterias uterinas, presión arterial media materna, factor de crecimiento placentario y proteína plasmática A asociada al embarazo, a fin de valorar el desempeño diagnóstico del modelo corregido de preeclampsia de la Fetal Medicine Foundation en población mexicana. MATERIALES Y MÉTODOS: Estudio de casos y controles anidado en una cohorte prospectiva efectuado en el Centro de Salud Dr. Galo Soberón y Parra entre el 1 de octubre de 2015 y el 30 de junio de 2016. Criterio de inclusión: pacientes con embarazo de 11-13.6 semanas. Criterio de exclusión: pacientes de riesgo no seleccionado, con embarazo único, entre 11 y 13.6 semanas calculadas por ecografía mediante longitud cráneo cauda. Criterio de eliminación: pacientes que abandonaron el estudio. Se evaluaron el índice de pulsatilidad medio de las arterias uterinas, la presión arterial media, los valores séricos del factor de crecimiento placentario y la proteína plasmática A asociada al embarazo. Se comparó la diferencia en la distribución de los biomarcadores entre la observada en población mexicana y la esperada según la formula original de la Fetal Medicine Foundation. Cuando la diferencia fue mayor a 0.2 múltiplos de la mediana, se utilizó la mediana del observado como coeficiente de ajuste a la fórmula original del esperado. RESULTADOS: De las 300 pacientes reclutadas, 292 concluyeron el estudio. La media de semanas de embarazo al momento del tamizaje fue de 12.4 (desviación estándar 0.72). La prevalencia de preeclampsia fue de 4.5% (13 de 292). Se encontraron diferencias importantes en la distribución de múltiplos de la mediana para el índice de pulsatilidad medio de las arterias uterinas, factor de crecimiento placentario y proteína plasmática A asociada al embarazo. Posterior a la corrección de los biomarcadores, la sensibilidad, falsos positivos y área bajo la curva del modelo ajustado para detectar cualquier preeclampsia fue de 92% (12 de 13), 5.7% (16 de 279) y 93.3%, respectivamente. CONCLUSIONES: La distribución de los múltiplos de la mediana en población mexicana es distinta para los biomarcadores: factor de crecimiento placentario, proteína plasmática A asociada al embarazo e índice de pulsatilidad medio de las arterias uterinas. El ajuste de estos biomarcadores para población mexicana resulta en un buen desempeño diagnóstico del modelo de preeclampsia.

Abstract OBJECTIVE: Calculate and adjust the multiples of the median (MoMs) for the mean pulsatility index of uterine arteries (IPm Aut), mean arterial pressure (PAM), placental growth factor (PlGF) and plasma protein associated with pregnancy (PAPP-A), in order to assess the diagnostic performance of the corrected preeclampsia model of the fetal medicine foundation in the Mexican population. MATERIALS AND METHODS: Case-control study nested in a prospective cohort conducted at the "Dr. Galo Soberón y Parra "from October 1, 2015 - June 30, 2016. Patients with pregnancy of 11-13.6 weeks were included, multiple pregnancies or older than 14 weeks were excluded and patients with medication intake prior to pregnancy; Patients who decided to leave the study were eliminated. Autm IPm, PAM, PlGF and PAPP-A serum values were evaluated. The difference in the distribution of biomarkers between that observed in the Mexican population and that expected was compared according to the original formula of the Fetal Medicine Foundation. When the difference was greater than 0.2 MoMs, the median observed was used as an adjustment coefficient to the original expected formula. RESULTS: Of the 300 patients recruited, 292 concluded the study. The average gestational age at the time of screening was 12.4 weeks (standard deviation [SD] 0.72). The prevalence of preeclampsia was 4.5% (13/292). Important differences were found in the distribution of multiples of the median (MoMs) for IPm Aut, PlGF and PAPP-A. After correction of the biomarkers, the sensitivity, false positives and area under the curve (AUC) of the model adjusted to detect any preeclampsia was 92% (12/13), 5.7% (16/279) and 93.3%, respectively . CONCLUSIONS: The distribution of MoMs in the Mexican population is different for the PlGF, PAPP-A and IPm Aut biomarkers. The adjustment of these biomarkers to the Mexican population results in a good diagnostic performance of the preeclampsia model.

Reference centile charts of first-trimester aneuploidy screening & Doppler parameters for Indian population

Background & objectives: The risk estimation for foetal aneuploidies in the first trimester of pregnancy uses reference curves based on western data. The objective of this study was to construct the reference curves of first-trimester foetal aneuploidy screening parameters for the Indian women. Methods: Cross-sectional data were obtained from 1204 singleton pregnancies between the crown-rump length (CRL) of 40-84 mm. Linear regression models were constructed; the mean, median and standard deviation were derived as a function of CRL. Results: The mean value of CRL was 61.3 mm. The regression analysis showed a significant correlation between all variables and CRL (P< 0.001). There was a positive correlation of CRL with nuchal translucency (NT) (y=0.010x+0.629, R2=0.116) and pregnancy-associated plasma protein-A (PAPP-A) (y=0.107x?1.079, R2=0.173), whereas inverse correlation was seen with free ?-human chorionic gonadotropin (?-hCG) (y=?0.409x+75.025, R2=0.018) and Doppler parameters pulsatility index (PI) (y=?0.008x+1.924 R2=0.053). The centile charts of NT, PAPP-A, free ?-hCG and uterine artery (Ut A) Doppler PI were constructed. Interpretation & conclusions: The reference centile charts of first trimester aneuploidy screening along with Doppler parameters were derived in Indian pregnant women. These centile charts may be used as a reference for clinical use in Indian population.

Diagnostic value of heart fatty acid binding protein and pregnancy associated plasma protein A in acute coronary syndrome / 国际检验医学杂志

Objective To investigate the clinical significance of heart fatty acid binding protein (H-FABP) and pregnancy associ-ated plasma protein A(PAPP-A) in acute coronary syndrome(ACS) .Methods A case-control study was conducted in 60 patients with ACS ,45 patients with stable angina pectoris (SAP) and50 patients without coronary heart diseases (control group) .All plasma samples were tested H-FABP and PAPP-A .Results Concentrations of H-FABP and PAPP-A were significantly different among the 3 groups(P<0 .01) .H-FABP and PAPP-A in ACS group were significant higher than those of SAP group and control group (P<0 .01) ,however there were no significant differences between SAP and control group (P>0 .05) .The sensitivity and specificity of H-FABP were 91 .7% and 78 .0% respectively analyzed by ROC curve .Similarly ,the sensitivity and specificity of PAPP-A were 48 .3% and 98 .0% respectively .The correlation of H-FABP and PAPP-A was high(r=0 .835 ,P<0 .01) according to the analysis by Pearson correlation analysis .Conclusion Concentrations of plasma H-FABP and PAPP-A had close relationship with ACS ,the sensitivity of H-FABP was much higher ,both of which could be the potential biomarkers and contributed to the diagnosis of exist-ence and progress of ACS .

Diagnostic value of heart fatty acid binding protein and pregnancy associated plasma protein A in acute coronary syndrome / 国际检验医学杂志

Objective To investigate the clinical significance of heart fatty acid binding protein (H-FABP) and pregnancy associ-ated plasma protein A(PAPP-A) in acute coronary syndrome(ACS) .Methods A case-control study was conducted in 60 patients with ACS ,45 patients with stable angina pectoris (SAP) and50 patients without coronary heart diseases (control group) .All plasma samples were tested H-FABP and PAPP-A .Results Concentrations of H-FABP and PAPP-A were significantly different among the 3 groups(P<0 .01) .H-FABP and PAPP-A in ACS group were significant higher than those of SAP group and control group (P<0 .01) ,however there were no significant differences between SAP and control group (P>0 .05) .The sensitivity and specificity of H-FABP were 91 .7% and 78 .0% respectively analyzed by ROC curve .Similarly ,the sensitivity and specificity of PAPP-A were 48 .3% and 98 .0% respectively .The correlation of H-FABP and PAPP-A was high(r=0 .835 ,P<0 .01) according to the analysis by Pearson correlation analysis .Conclusion Concentrations of plasma H-FABP and PAPP-A had close relationship with ACS ,the sensitivity of H-FABP was much higher ,both of which could be the potential biomarkers and contributed to the diagnosis of exist-ence and progress of ACS .

Risk assessment for preeclampsia by biochemical and biophisycal markers at first trimester / Монголын Анагаах Ухаан

Introduction@#Preeclampsia, which affects about 2-8% of pregnancies, is major cause of maternal and perinatal morbidity and mortality, particularly in developing countries. In Mongolia, preeclampsia and eclampsia occurred among pregnancy complications about 25% in recent years. There is a percentage for a cause of maternal death was 17.7% in preeclampsia and eclampsia between 2012 and 2015 in Mongolia.</br> Effective prediction of preeclampsia can be achieved at 11-13 week’s gestation by combination of maternal characteristics, mean arterial pressure (MAP), uterine artery pulsatility index (UtA PI), maternal serum placental growth factor (PlGF), and pregnancy-associated plasma protein-A (PAPP-A).@*Goal@#To investigate plasma concentration of PIGF and PAPP-A, in pregnant women at 11-13+6 of gestation for screening of preeclampsia, To examine the performance of first-trimester screening for preeclampsia based on maternal characteristics, MAP, and mUt.A-PI.@*Materials and Methods @#The study conducted among 393 single pregnant women at 11-13+6 weeks, who were visiting antenatal care services, between March, 2015 and June, 2017. The prospective Cohort research method was used for this study. Written informed consent was obtained from all participants. Maternal plasma PAPP-A, PlGF were determined using Perkin Elmer kits by fluoroimmunoassay.</br> Measurement of MAP was by validated automated devices (HEM-7120, Оmron, Japan). MAP was calculated from the formula DP + 1/3*(SP-DP), where DP represents diastolic blood pressure and SP- systolic blood pressure. Trans-abdominal ultrasound (Voluson E8, GE, USA) examination was carried out for Ut.A-PI.@*Results@#In the study population, there were 66 (16.8%) cases that experienced preeclampsia and 327 (83.2%) cases that were unaffected by preeclampsia. The result showed that the mean concentration of PlGF was 38.6±19.6 pg/ml in PE group whereas the mean was 45.1±24.0 pg/ml in normal pregnant women. Level of PAPP-A was 366.1±195.3 mU/L in group with PE, 633.6±496.9 mU/L in group without preeclampsia. </br> The best Youden’s index and area under the curve (AUC) for MAP and mUt.A-PI were as a predictor of PE. It can be shown that the cutoff point for MAP was 89.5 mmHg (sensitivity-71.2%; specificity-75.5% J-0.467; AUC-0.792; P<0.001). The cutoff point of mUt.A-PI was 2.34 (sensitivity-33.3%; specificity-77.7% J-0.12; AUC-0.577; P<0.001).@*Conclusions@#The concentration of PIGF and PAPP-A in pregnant women with preeclampsia at 11-13+6 of gestation was lower than normal pregnant women. The detection risk of PE by MAP is more accurate than the mUtA-PI measurement.

Predictive value of pregnancy-associated plasmaprotein-A and global registry of acute coronary events risk score on major adverse cardiac events in patients with acute myocardial infarction / 中国介入心脏病学杂志

Objective To investigate the predictive value of pregnancy-associated plasmaprotein-A (PAPP-A) and GRACE risk score for death and nonfatal myocardial infarction (combined endpoint) in AMI patients.Methods All AMI patients hospitalized in our department during July 2011 to July 2015 were included consecutively in this prospective study.Plasma PAPP-A were measured at admission.GRACE risk score was acquired with the application of GRACE risk score calculator.Patients were followed up for at least 1 year for any nonfatal myocardial infarction or MACE.Kaplan Meier survival study was analysed according to PAPP-A and GRACE score risk stratification respectively.A cutoff value of 3.0 ng/ml of PAPP-A was chosen from pilot work in this cohort.Results A total of 220 patients were enrolled in the study.The death and nonfatal myocardial infarction during follow-up were significantly higher in patients with PAPP-A≥3.0 ng/ml compared to patients with PAPP-A<3.0 ng/ml (15.7% vs.6.0%, log-rank χ2=5.684, P=0.017).The area under ROC curve of PAPP-A was 0.796(95%CI 0.696-0.896, P<0.01) and the ROC curve of PAPP-A GRACE risk stratification was 0.715 (95%CI 0.567-0.863,P<0.01).Subgroup analysis showed that death and nonfatal myocardial infarction during follow-up was significantly higher in patients with PAPP-A≥3.0 ng/ml compared to patients with PAPP-A<3.0 ng/ml in intermediate and low risk group by GRACE risk stratifcation (log-rank χ2=14.63,P<0.001).Conclusions PAPP-A could predict mortality and nonfatal myocardial infarction in patients with AMI.PAPP-A combined with GRACE risk score can better predict outcome than GRACE risk score alone in intermediate and low risk patients by GRACE risk stratifcation.

Maternal serum placental growth factor and pregnancy-associated plasma protein A measured in the first trimester as parameters of subsequent pre-eclampsia and small-for-gestational-age infants: A prospective observational study

OBJECTIVE: To examine the first-trimester maternal serum placental growth factor (PlGF) and pregnancy-associated plasma protein A (PAPP-A) levels in pregnancies associated with pre-eclampsia (PE) or small-for-gestational-age (SGA) infants, and determine the predictive accuracy of PlGF and of PAPP-A for either PE or SGA infants. METHODS: This prospective, observational study included 175 pregnant women, and of these women, due to participant withdrawal or loss to follow-up, delivery data were collected from the medical records of 155 women, including 4 who had twin pregnancies. The women's maternal history was recorded, and the PlGF and PAPP-A levels at 11 to 13 gestational weeks were measured. During the second trimester, the maternal uterine artery's systolic/diastolic ratio was measured. Multiples of the median (MoM) of PlGF and PAPP-A were determined, and the associations of these values with the risk factors of SGA and PE were evaluated. Logistic regression analysis was used to determine whether PlGF and PAPP-A are useful markers for predicting SGA infants. RESULTS: The PAPP-A MoM level was significantly lower in women with advanced maternal age, multipara women, and women with gestational diabetes than in their counterparts. The PlGF and PAPP-A MoM levels were higher in women with a twin pregnancy than in those with a singleton pregnancy. There was a significant relationship between the maternal serum PAPP-A MoM level in the first trimester and the uterine artery systolic/diastolic ratio in the second trimester. Results of logistic regression analysis showed that low PlGF and PAPP-A MoM levels were predictors of SGA infants (odds ratio, 0.143; 95% confidence interval, 0.025 to 0.806; odds ratio, 0.191; 95% confidence interval, 0.051 to 0.718, respectively). CONCLUSION: PlGF and PAPP-A are potentially useful as first-trimester markers for SGA infants and some hypertensive disorders of pregnancy.

Asociación entre el sistema IGF y PAPP-A en ateroesclerosis coronaria / Association between IGF system and PAPP-A in coronary atherosclerosis

Resumen La aterosclerosis es una enfermedad que involucra múltiples mecanismos fisiopatológicos cuyo conocimiento no se ha dilucidado por completo. Con frecuencia, los avances científicos sobre la fisiopatología aterogénica generan que a diversas moléculas no consideradas previamente en el panorama de dicha enfermedad se les atribuyan acciones sobre el inicio o progresión de la misma. Un ejemplo representativo es el estudio de un nuevo mecanismo involucrado en el proceso aterogénico, consistente en la asociación entre el sistema de factores de crecimiento similares a la insulina (IGF) y la proteína plasmática A asociada al embarazo (PAPP-A). El sistema IGF es una familia de péptidos compuesto por 3 hormonas peptídicas, 4 receptores transmembranales y 6 proteínas transportadoras. El factor de crecimiento similar a la insulina tipo 1 (IGF-1) es el principal ligando del sistema IGF involucrado en la aterosclerosis coronaria y ejerce sus efectos mediante la activación del receptor IGF-1R en células de músculo liso vascular de las arterias coronarias o en macrófagos de placas ateroscleróticas. En células de músculo liso vascular promueve la migración y previene la apoptosis aumentando la estabilidad de la placa, y en macrófagos disminuye el transporte reverso de colesterol propiciando la formación de células espumosas. La regulación de la biodisponibilidad de IGF-1 en el endotelio se lleva a cabo por las proteasas de proteínas IGFBP, principalmente por la PAPP-A. En la presente revisión se abordan los mecanismos involucrados entre el sistema IGF y la PAPP-A en aterosclerosis coronaria con énfasis en los efectos moleculares producidos en células de músculo liso vascular y en macrófagos.

Abstract Atherosclerosis is a condition that involves multiple pathophysiological mechanisms and whose knowledge has not been fully elucidated. Often, scientific advances on the atherogenic pathophysiology generate that molecules not previously considered in the scene of this disease, were attributed actions on the onset or progression of it. A representative example is the study of a new mechanism involved in the atherogenic process, consisting of the association between the insulin-like growth factor (IGF) system and pregnancy-associated plasma protein-A (PAPP-A). Insulin-like growth factor system is a family of peptides that include 3 peptide hormones, 4 transmembrane receptors and 6 binding proteins. Insulin-like growth factor-1 (IGF-1) is the main ligand of the IGF system involved in coronary atherosclerosis. IGF-1 exerts its effects via activation of the IGF-1R receptor on vascular smooth muscle cells or macrophages. In vascular smooth muscle cells promotes migration and prevents apoptosis which increases plaque stability while in macrophages reduces reverse cholesterol transport leading to the formation of foam cells. Regulation of IGF-1 endothelial bioavailability is carried out by IGFBP proteases, mainly by PAPP-A. In this review, we address the mechanisms between IGF system and PAPP-A in atherosclerosis with emphasis on molecular effects on vascular smooth muscle cells and macrophages.

Relationship between serum PAPP-A expression and gene polymorphism with severity of coronary lesions in patients with coronary heart disease / 重庆医学

Objective To investigate the relationship between serum pregnancy associated plasma protein A (PAAA‐A) ex‐pression and gene polymorphism with the severity of coronary lesions in the patients with coronary heart disease (CHD) .Methods Ninety‐eight patients with CHD in the Nanyang Municipal Central Hospital were selected as the observation group and divided into single vessel lesion group and multiple vessel lesion group according to coronary angiographic results .Ninety‐eight individuals un‐dergoing healthy physical examination were selected as the control group .The venous blood was collected at the visiting hospital in the observation group and at the physical examination in the control group for detecting the serum PAPP‐A protein level by ELISA .PAPP‐A gene and IVS6+ 95 polymorphism were analyzed by adopting polymerase chain reaction restriction fragment length polymorphism(PCR‐RELP) .Results Compared with the control group ,peripheral blood PAPP‐A protein level in the obser‐vation group was significantly increased(P<0 .05) ,moreover the PAPP‐A protein level in the multiple vessel lesion group was sig‐nificantly higher than that of the single vessel lesion group (P<0 .05) .The peripheral blood PAPP‐A level was positively correlated with the severity of CHD .Three genotypes existed in PAPP‐A gene IVS6+95 locus ,including CG heterozygous ,homozygous CC and GG homozygous type .The CC homozygous allele frequency in the patients with multiple vessel lesion was higher than that in the patients with single vessel lesion (P<0 .05) .Conclusion The PAPP‐A protein level and IVS6+95 polymorphism have a close relation with the severity of coronary lesions in patients with CHD .CC genotype may be one of genetic susceptibility gene markers in the patients with CHD .

Application value of serum pregnancy-asscociated plasma protein A in primiparous women of gestational diabetes mellitus / 国际检验医学杂志

Objective To assess the correlation between the pregnancy‐associated plasma protein A (PAPP‐A)level with gesta‐tional diabetes mellitus(GDM )in primiparous women .Methods The nonparametric test and Logistic regression analysis were used to retrospectively analyze 168 pregnant women of GDM and 273 normal pregnant women ,including age ,body weight ,PAPP‐A ,freeβ‐human chorionic gonadotropin(fβ‐hCG) .Results The age had significant difference between GDM group and control group(P<0 .01) ,the PAPP‐A concentration and corrected multiple of the median (MoM )of PAPP‐A in the GDM group were significantly lower than those in the control group(P<0 .01) .Conclusion Low level of PAPP‐A during early pregnant stage in primiparas is strongly associated with GDM and can be used as the risk factor of GDM .

Serum levels and clinical signiifcance of IGF1, IGFBP-4 and PAPPA in non-small cell lung cancer / 中国癌症杂志

Background and purpose:It is increasingly focused on that insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 4 (IGFBP-4) effect cell proliferation, differentiation and apoptosis of tumor cells, and pregnancy-associated plasma protein-A (PAPPA) plays an important role in IGF-1-dependent IGFBP-4 protease mechanism that regulats tumor cells' growth. This study aimed to investigate the serum levels and clinical signiifcance of IGF-1, IGFBP-4, and PAPPA in patients with non-small cell lung cancer (NSCLC). Methods:IGF-1, IGFBP-4, and PAPPA plasma levels were measured by enzyme-linked immunosorbent assay from 82 patients with NSCLC and 40 control subjects, then the correlations between variables were assessed by Spearman correlation analysis, and associations between the IGFs variables and lung cancer risk were calculated through the odds ratio (OR) and its 95%conifdence interval (CI) with the use of unconditional logistic regression analysis. Results:Serum levels of IGF-1, IGFBP-4 and PAPPA in NSCLC patients were signiifcantly higher than those in the control group(P<0.05). There was a signiifcant positive correlation between the serum IGF-1 levels and PAPPA levels (r=0.835,P=0.000), and a negative correlation with IGFBP-4 levels (r=-0.612,P=0.000). IGFBP-4 and PAPPA levels were negatively correlated(r=-0.673, P=0.000). High plasma levels of IGF-1(OR=2.28, 95%CI: 1.25-4.36,P=0.008) and PAPPA (OR=1.64, 95%CI: 0.89-3.01,P=0.046)were associated with an increased risk of lung cancer, however high plasma levels of IGFBP-4(OR=0.54, 95%CI:0.30-1.01,P=0.047)were associated with reduced risk of lung cancer. Conclusion:To detect IGF-1, IGFBP-4 and PAPPA in serum in NSCLC patients is meaningful for the clinical auxiliary diagnosis and biology behavior prediction of NSCLC. And further study of signal transduction pathways of IGFs with the occurrence and development of NSCLC is a meaningful research direction.

Proteína plasmática A asociada al embarazo y fracción β de gonadotrofina coriónica humana en pacientes con resultados materno y perinatal adverso: informe preliminar / Plasma protein associated with pregnancy and β fraction human chorionic gonadotropin results in patients with adverse maternal and perinatal: preliminary report

Objetivo: Evaluar el comportamiento de marcadores bioquímicos: proteína plasmática asociada al embarazo (PAPP-A) y fracción β de la hormona gonadotrofina coriónica (β hCG) con resultado materno y perinatal adverso en el Hospital “Dr. Adolfo Prince Lara”. Métodos: Estudio prospectivo, comparativo en 35 gestantes con embarazos simples entre las 11 y 13 semanas + 6 días y resultado del embarazo conocido. Se realizó tamizaje combinado: traslucencia nucal, hueso nasal, ductus venoso, longitud craneocaudal y marcadores bioquímicos (PAPP-A y β -hCG). Se determinó la concentración de PAPP-A y β -hCG y sus resultados se expresaron en MoM. Variables cuantitativas fueron expresadas en media y desviación estándar (DE), cualitativas en porcentajes y se compararon estas variables entre el grupo de gestantes con resultado materno perinatal normal (RMPN) y adverso (RMPA) con la prueba U de Mann-Whitney. Resultados: 71 % tuvieron un RMPN y 29 % RMPA. No se encontraron diferencias entre los grupos respecto a edad materna, peso materno, IMC, paridad, presión arterial. La PAPP-A expresado en MoM presentan un valor más alto en las embarazadas que tuvieron un RMPA (1,07 vs 1,43) siendo estadísticamente significativo, los valores de β-HCG tuvieron valores más altos (0,60 vs 0,76) entre el grupo con RMPA en relación al grupo con RMPN sin llegar a la significancia estadística. Conclusión: Valores de la MoM PAPP-A difieren en las embarazadas con RMPA de aquellas con resultado normal, pero con valores mayores en las primeras, contrario a lo encontrado en la mayoría de las publicaciones estudiadas, iguales hallazgos con la β-hCG. Se debe profundizar en estos estudios para verificar los resultados encontrados.

Objective: To evaluate the behavior of biochemical markers PAPP-A and β hCG with adverse pregnancy and perinatal outcomes. Methods: Prospective, comparative study in 35 pregnant women with singleton pregnancies between 11 and 13 weeks + 6 days and outcome of pregnancy known. Nuchal translucency, nasal bone, ductus venosus, rump length and biochemical markers (PAPP-A and β-hCG) combined screening was performed. The concentration of PAPP-A and β-hCG was determined and the results were expressed in MoM. Quantitative variables were expressed as mean and standard deviation (SD), and these percentages qualitative variables between the group of pregnant women with a normal perinatal maternal outcome (NPMO) and adverse (AMPO) with the U Mann-Whitney test were compared. Setting: Hospital “Dr. Adolfo Prince Lara”. Results: 71 % had a NPMO and 29 % had an AMPO. No differences between the groups in respect of maternal age, maternal weight, BMI, parity, blood pressure were found. PAPP-A MoM have expressed a higher value in pregnant having an AMPO (1.07 vs 1.43) were statistically significant, the values of β-HCG had higher values (0.60 vs 0.76) between the group with AMPO relative to NMPO group without reaching statistical significance. Conclusion: MoM values of PAPP-A differ in pregnant with AMPO than in those with normal results, but with higher values in the first opposite to that found in most of the studied publications, the same findings with β-hCG. Thus, it should look into these studies to verify the results found.

Effect of salvianolate injection on serum levels of pregnancy associated plasma protein A , brain natriuretic peptide and high sensitively C-reactive protein in elderly patients with acute myocardial infarction / 中华老年医学杂志

Objective To observe the effects of salvianolate injection on blood levels of high sensitively C-reactive protein (hs-CRP),pregnancy associated plasma protein-A (PAPP-A) and brain natriuretic peptide (BNP) in elderly patients with acute myocardial infarction.Methods The elderly patients with AMI (AMI group,n=160) and healthy controls (control group.n=30) were enrolled in this study and their blood concentrations of PAPP A,hs CRP and BNP were detected before and two weeks after treatment.The elderly patients in AMI group were randomized into conventional treatment group (n =80) and salvianolate group (n =80).Results The levels of PAPP-A,hs-CRP and BNP were significantly higher in AMI patients [(12.88±2.56) mg/L,(20.13 ±5.35) mU/L,(412.0±69.5) ng/L,respectively] than in healthy subjects[(1.20±0.88) mg/L,(1.90±0.46) mU/L,(89.0±5.6) ng/L,respectively] (t=24.670,3.780,11.939,respectively,P ＜0.01).But,before treatment there were no significant differences in the levels of PAPP-A,hs-CRP and BNP between the AMI group and control group (t=0.864,0.712,0.985,all P＞0.05).After two weeks of treatment,as compared with control group,AMI group showed that the serum concentrations of PAPP-A,hs-CRP and BNP were decreased significantly (P＜0.05).The levels of PAPP A,hs-CRP and BNP were (3.83±1.20) mg/L,(1.33±0.38) mU/L,(105.0±31.2) ng/L in salvianolate group and (5.71± 1.93) mg/L,(1.81±0.72) mU/L,(150.0±36.7) ng/L in conventional treatment group respectively,and the decrements in levels of PAPP-A,hs CRP and BNP were greater in the former than in the latter(t=7.399,5.273,8.356,respectively,all P＜0.05).Conclusions The dynamic serum concentrations of PAPP-A,hs CRP and BNP can be used as clinical indexes for the prognosis of acute myocardial infarction.Salvianolate injection can significantly decrease the serum levels of PAPP A,hs CRP and BNP.The salvianolate injection may have anti inflammatory effect and improve cardiac function in elderly patients with acute myocardial infarction,but the mechanism is still to be further discussed.

The relationship between serum pregnancy associated plasma protein A level and pregnancy outcomes in early pregnancy / 中国医师进修杂志

Objective To explore the relationship between pregnancy associated plasma protein A (PAPP-A) and threatened abortion,whether low level of PAPP-A in early pregnancy can be used as indicators to predict the pregnancy outcomes.Methods The level of serum PAPP-A was measured by double antibody sandwich enzyme-linked immunosorbent assay in 110 cases with threatened abortion (threatened abortion group) and 131 cases with normal intrauterine pregnancy (control group),and track to 20 weeks pregnant.Results The serum PAPP-A multiple of median (MOM) value was 1.02 ± 0.15 in control group,0.98 ± 0.17 in threatened abortion group,and there was no significant difference(P ＞ 0.05).In threatened abortion group,90 cases of spuc success,the serum PAPP-A MOM value was 1.03 ± 0.11,20 patients of spuc failure,the serum PAPP-A MOM value was 0.73±0.21,and there was significant difference (P ＜ 0.01).There was no significant difference in the serum PAPP-A MOM value between control group and the spuc success of threatened abortion group (P ＞ 0.05).Conclusion Pregnant women with PAPP-A levels embryonic development is closely related to the good,as one can predict miscarriage in pregnant women with threatened abortion outcome evaluation.

Relationships between plasma soluble CD40 ligand, fetuin-A and pregnancy-associated plasma protein A and carotid artery plaque in patients with ischemic stroke / 国际脑血管病杂志

Objective To investigate the relationships between the levels of plasma soluble CD40 ligand (sCD40L),fetuin-A and pregnancy-associated plasma protein A (PAPP-A) and carotid plaque in patients with acute ischemic stroke.Methods The patients with acute ischemic stroke were enrolled in the study.Carotid arteries were assessed by using carotid artery ultrasound.The patients were divided into either a carotid artery plaque group or a non-carotid artery plaque group according to the assessment results.The former were further divided into a stable plaque sub-group and an unstable plaque sub-group according the nature of plaque.Enzyme-linked immunosorbent assay was used to detect the levels of plasma sCD40L,fetuin-A and PAPP-A.The demography,previous history,complications,laboratory tests and plasma inflammatory biomarkers between the carotid artery plaque group and the non-carotid artery plaque group and between the stable plaque subgroup and the unstable plaque subgroup were compared.Multivariate logistic regression analysis was used to investigate the relationship between plasma inflammatory biomarkers and carotid plaques.Results A total of 200 patients with acute ischemic stroke were included.Among them,78 were females and 122 were males (aged 33 to 87 years,mean 60.1 ± 10.3 years); 139 patients were in the carotid artery plaque group and 61 were in the non-plaque group; 43 were in the stable plaque subgroup and 96 were in the unstable plaque subgoup.The mean age of the carotid artery plaque subgroup was significantly greater than that in the non-plaque subgroup (63.2 ± 8.7 years vs.50.3 ± 9.5 years; t ＝ 10.179,P =0.000),the constituent ratios of men (68.3％ vs.44.3％;x2＝ 10.336,P＝ 0.001),hypertension (71.2 vs.54.1％;x2=5.540,P=0.019),diabetes (46.8％ vs.29.5％ ;x2 =5.199,P =0.023),and hyperlipidemia (78.4％ vs.37.7％ ;x2 =31.31,P =0.000)in patients of carotid plaque group were significantly higher than those of the non-carotid plaque group.The levels of total cholesterol (5.7 ± 1.1 mmol/L vs.5.3 ± 1.0 mmol/L; t =2.433,P =0.016),low-density lipoprotein cholesterol (4.5 ± 1.0 mmol/L vs.4.1 ±0.9 mmol/L; t =2.683,P =0.008),fasting glucose (7.5 ±2.5 mmol/Lvs.6.4±2.1 mmol/L; t=3.002,P＝0.003),sCD40L (151.4 ± 55.8 pg/mlvs.102.8 ±65.9 pg/ml; t =5.360,P=0.000),fctuin-A (390.1 ± 80.6 μg/ml v.s.352.9 ± 98.6 μg/ml; t =2.591,P =0.011),and PAPP-A (11.49 ±4.67 mIU/L vs.8.46 ± 3.99 mIU/L; t =4.409,P =0.000) were significantly higher than those of the non-carotid plaque group.Multivariate logistic regression analysis showed that hyperlipidemia (odds ratio [OR] 6.582,95％ confidence interval [CI] 2.321-18.662; P =0.000),sCD40L (OR6.372,95％ CI 2.174-18.670;P=0.010),and fetuin-A (OR 4.101,95％ CI 1.012-16.619; P=0.048) were the independent predictors for carotid artery plaques in patients with acute ischemic stroke.The mean age of the stable plaque subgroup was significantly lower than that of the unstable plaque subgroup (59.6 ± 9.3 years vs.64.1 ± 7.2 years; t =3.231,P =0.002).The constituent ratio in patients with hypertension was significantly lower than that of the unstable plaque subgroup (55.8％ vs.78.1％ ; x2 =7.213,P =0.007).The levels of total cholesterol (5.4 ±0.9 mmol/L vs.6.0 ± 1.1 mmol/L; t =3.136,P =0.002),low-density lipoprotein cholesterol (4.0 ± 1.2 mmol/L vs.5.7 ± 1.0 mmol/L; t =8.696,P =0.000),fasting glucose (7.1 ± 2.3 mmol/L vs,7.9 ± 1.9 mmol/L; t =2.147,P =0.034),sCD40L (135.3 ±74.3 pg/ml vs.176.5 ±64.5 pg/ml; t =3.319,P ＝0.001),and PAPP-A (10.96 ± 5.02 mIU/L vs.13.98 ±4.63 mIU/L; t =3.463,P =0.001) were significantly lower than those of the unstable plaque subgroup,while the level of high-density lipoprotein cholesterol was significantly higher than that of the unstable plaque subgroup (1.2 ± 0.2 mmol/L vs.1.1 ± 0.3 mmol/L; t =2.314,P=0.022).Multivariate logistic regression analysis showed that HDL-C (OR 0.234,95％ CI0.060-0.906; P =0.022) was an independent protective factor for unstable plaques,while sCD40L (OR 5.290,95％ CI 1.613-17.351; P =0.029) and PAPP-A (OR4.125,95％ CI 1.281-13.283; P =0.021) were the independent predictors for unstable plaques.Conclusions The levels of sCD40L,PAPP-A,and fetuin-A were associated with the existence and stability of carotid artery plaque.The increased plasma sCD40L and fetuin-A were the independent predictors for carotid artery plaques in patients with acute ischemic stroke,and the increased levels of plasma sCD40L and PAPP-A were the independent predictors for carotid artery plaque instability in patients with acute ischemic stroke.

Effect of PAS therapy on serum related protein levels and carotid vulnerable plaque in patients with acute cerebral infarction / 中华神经医学杂志

Objective To observe the influence of combination therapy ofprobucol,aspirin and statins drugs (PAS) on levels of serum oxidized low-density lipoproteins (ox-LDL),pregnancy-associated plasma protein A(PAPP-A) and marix metalloproteinase-3(MMP-3) and resolution of carotid vulnerable plaque in patients with acute cerebral infarction (ACI).Methods One hundred and thirty-five patients with ACI,admitted to our hospital from September 2007 to July 2010,were chosen in our study; according to the results of carotid artery ultrasound,these patients were divided into carotid stable plaque group (n=45) and carotid vulnerable plaque group (n=90).Stable plaque group was considered as control group; 90 patients with carotid vulnerable plaque were randomly subdivided into aspirin and statins drugs (AS) group (n=45,aspirin 100 mg/d,atorvastatin 20 mg/d,orally) and PAS group (n=45,aspirin 100 mg/d,atorvastatin 20 mg/d,probucol 0.25 g/time,2 times/day,orally).Levels ofOx-LDL,PAPP-A and MMP-3 were detected in all patients before treatment and four weeks after drug therapy.The intima-media thickness,plaque area and echogenicity of carotid plaques were evaluated by Doppler ultrasonography during a 12-month follow-up period.Results Before treatment,serum ox-LDL,PAPP-A and MMP-3 levels in AS group and PAS group were significantly higher than those in the control group (P＜0.05); no significant differences of ox-LDL,PAPP-A and MMP-3 levels were noted between AS and PAS groups (P＞0.05).Four weeks after treatment,levels of serum ox-LDL,PAPP-A and MMP-3 in PAS group were significantly lower than those in AS and control groups (P＜0.05); the decrease of levels of ox-LDL,PAPP-A and MMP-3 in PAS group was obviously higher than that in AS and control groups (P＜0.05).Twelve months after treatment,significant decrease of plaque area and intima-media thickness (IMT) was noted in the AS and PAS groups (P＜0.05); the IMT and plaque area in PAS group were significantly smaller than those in AS group (P＜0.05); obvious decrease of echogenicity of carotid plaques in PAS group was noted as compared with that in AS group (P＜0.05).Conclusion Combination therapy of PAS might have strong anti-oxidant function and lipid-lowering effect,which could reverse and stabilize the atherosclerosis plaque.