Níveis mais Baixos de Fetuína-A Sérica estão Associados a um Maior Risco de Mortalidade em Dez Anos em Pacientes com Infarto do Miocárdio por Supradesnivelamento do Segmento ST / Lower Serum Fetuin-A Levels are Associated with a Higher Ten-Year Mortality Risk in Patients with ST-Elevation Myocardial Infarction

Resumo Fundamento A fetuína-A é um fator anti-inflamatório e anticalcificação envolvido no curso da doença arterial coronariana (DAC). Em alinhamento com essas funções, investigou-se a fetuína-A como marcador de risco cardiovascular em vários estudos. Porém, a associação entre a fetuína-A e o prognóstico dos pacientes com DAC ainda é controversa. Objetivos O presente estudo foi conduzido para identificar a associação entre o nível de fetuína-A sérica e doença cardiovascular (DCV) de longo prazo e a mortalidade global por infarto do agudo do miocárdio por supradesnivelamento do segmento ST (STEMI). Métodos Foram cadastrados no estudo cento e oitenta pacientes consecutivos com STEMI. A população do estudo foi dividida em subgrupos (mais baixo, ≤288 µg/ml; e mais alto, >288 µg/ml) de acordo com a mediana do nível de fetuína-A. Dados de acompanhamento clínico foram obtidos por contato telefônico anual com pacientes ou familiares. As causas das mortes também foram confirmadas pelo banco de dados de saúde nacional. P-valores bilaterais <0,05 foram considerados estatisticamente significativos. Resultados Durante um acompanhamento médio de 10 anos, foram registradas 71 mortes, das quais 62 foram devidas a DCV. Identificou-se um índice de mortalidade global e por DCV significativamente mais alto no grupo com nível de fetuína-A mais baixo que no grupo com nível de fetuína-A mais alto (44% versus 24%, p= 0,005; 48% versus 31%, p= 0,022, respectivamente). Nas análises de risco proporcionais por regressão de Cox, detectou-se que a fetuína-A era um preditor independente de mortalidade global e por DCV. Conclusões A baixa concentração de fetuína-A está associada ao prognóstico de longo prazo ruim pós-STEMI, independentemente de fatores de risco cardiovascular tradicionais. Nossos achados fortaleceram estudos prévios demonstrando consistentemente o papel determinante dos mediadores anti-inflamatórios em síndromes coronárias agudas.

Abstract Background Fetuin-A is an anti-inflammatory and anti-calcification factor involved in the course of coronary artery disease (CAD). In line with these functions, fetuin-A has been investigated as a cardiovascular risk marker in many studies. However, the association between fetuin-A and the prognosis of CAD patients is still controversial. Objectives The present study was conducted to identify the association between serum fetuin-A level and long-term cardiovascular disease (CVD) and all-cause mortality of ST-elevation acute myocardial infarction (STEMI). Methods One hundred eigthy consecutive patients with STEMI were enrolled in the study. The study population was divided into subgroups (lower, ≤288 µg/ml; and higher, >288 µg/ml) according to the median fetuin-A level. Clinical follow-up data was obtained by annual contact with the patients or family members by telephone. The causes of death were also confirmed by the national health database. Two-sided p-values<0.05 were considered statistically significant. Results During a median follow-up of 10 years, 71 deaths were recorded , 62 of whom died from CVD. Both CVD and all-cause mortality were found to be significantly higher in the lower fetuin-A group than the higher fetuin-A group (44% vs 24%, p= 0.005; 48% vs 31%, p= 0.022, respectively). In Cox regression proportional hazard analyses, fetuin-A was found to be an independent predictor of CVD and all-cause mortality. Conclusions Low fetuin-A concentration is associated with a poor long-term prognosis after STEMI, regardless of the traditional cardiovascular risk factors. Our findings have strengthened previous studies that consistently demonstrate the determining role of anti-inflammatory mediators in acute coronary syndromes.

Establishment of lectin-ELISA for sialylated fetuin-A and its diagnostic value in primary hepatocellular carcinoma / 中华检验医学杂志

Objective:To establish a lectin enzyme-linked immunosorbent assay (lectin-ELISA) for the dection of sialylated fetuin-A and to explore the clinical diagnostic value of sialylated fetuin-A in hepatocellular carcinoma (HCC).Methods:From January 2017 to December 2020, 300 HCC patients and 160 disease controls, including 36 liver cirrhosis subgroups and 124 chronic hepatitis B subgroups, were collected from Shanghai Eastern Hepatobiliary Surgery Hospital. At the same time, 100 healthy subjects were collected as healthy controls. Lectin-ELISA method for detecting sialylated fetuin A was established based on the principle that Sambucus nigra lectin (SNA) can recognize the structure of α-2, 6-linked sialic acid residues. Differences between groups were compared using t-test or analysis of variance. Logistic regression method was used to establish the multi-index joint detection model, and receiver operating characteristic curve (ROC) was used to evaluate the efficacy of single index and joint detection model in the diagnosis of HCC.Results:A lectin-ELISA method for the detection of serum Sia-fetuin A was established. The linear regression coefficient of the system was 0.978 5, and the precision evaluation and interference experiments were in line with the clinical detection requirements. Using this method to detect serum Sia-fetuin A levels in each group, the levels of HCC group, disease control group and healthy control group were 1.362±0.310, 1.199±0.370, 1.086±0.420, respectively, and the three groups decreased in turn. The areas under the curve of Sia-fetuin A, α-fetoprotein, and their combined detection models for differential diagnosis of HCC were 0.790, 0.809, and 0.860, respectively. The diagnostic model had a sensitivity of 79.3% (238/300) and a specificity of 95.0% (247/260). Among the 300 patients in the HCC group, 138 (46%) patients were negative for serum AFP (<20 μg/L), and their serum Sia-fetuin A level was 1.364±0.305. Combining the disease control group and the healthy control group into the non-Cancer group, the serum Sia-fetuin A level was 1.146±0.381. The serum level of Sia-fetuin A in AFP-negative HCC patients was higher than that in non-HCC group ( t=6.134, P<0.001). The areas under the curve of Sia-fetuin A and the combined diagnostic model for the diagnosis of AFP-negative HCC were 0.776 and 0.919, respectively. The combined diagnostic model had a sensitivity of 93.4% (129/138) and a specificity of 77.3% (201/260). Conclusion:Serum Sia-fetuin A and combined determination model can provide a new auxiliary diagnostic index for AFP-negative HCC.

Biomarkers of bone and mineral disorders (FGF-23, fetuin-A) and vascular calcification scores as predictive tools for cardiovascular death in dialysis patients, at 10 years of follow-up / Biomarcadores del metabolismo mineral óseo (FGF-23, fetuína-A) y calcificaciones vasculares como herramientas predictivas de muerte cardiovascular de pacientes en diálisis, a 10 años de seguimiento

Abstract Cardiovascular disorders represent the leading cause of death in dialysis patients. Alterations of bone and mineral metabolism (BMM) and vascular calcifications play a fundamental role in it. The objective of this study was to evaluate the predictive role on cardiovascular mortality of the measurement of biomarkers of BMM and vascular calcifications. A prospective cohort study was performed. All prevalent patients on chronic dialysis in September 2009 at our institution, who completed the total of the complementary stud ies, were studied. BMM biomarkers were measured (FGF 23, fetuin A, PTH, calcium and phosphorus) and the vascular calcifications were evaluated using the Kauppila and Adragao scores. Follow-up was carried out until 1/1/2019, death or transplant. Of the 30 patients included, 7 (23.3%) died due to cardiovascular causes. The follow-up time was 44.1 ± 30.4 (range = 1.4-112) months. The Adragao score was the only predictive variable of long-term cardiovascular mortality (area under the curve = 0.82; 95% CI 0.64-0.94; p < 0.001). The best cut-off point was 5 (sensitivity = 85.7%; specificity = 78.3%). It was also an independent risk factor for cardiovascular mortality adjusted for age, diabetes mellitus, coronary heart disease, aortic calcifications, time spent on dialysis and follow-up time (adjusted OR = 1.77; 95% CI = 1.06-2.96; p = 0.028). The vascular calcifications quantified from the Adragao score were the only independent predictor of long-term cardiovascular mortality. This score represents a simple, useful and superior tool to the biomarkers of BMM.

Resumen Los trastornos cardiovasculares representan la primera causa de muerte en los pacientes en diálisis. Las alteraciones del metabolismo óseo y mineral (MOM) y las calcificaciones vasculares juegan un papel fundamental en la misma. El objetivo de este estudio fue evaluar el rol predictor sobre la mortalidad car diovascular de la medición de los biomarcadores del MOM y las calcificaciones vasculares. Se realizó un estudio de cohorte prospectivo. Se estudiaron todos los pacientes prevalentes en diálisis crónica en septiembre del 2009 en nuestra institución que completaron el total de los estudios complementarios. Se midieron biomarcadores del MOM (FGF 23, fetuína A, PTH, calcio y fósforo) y se evaluaron las calcificaciones vasculares mediante los scores de Kauppila y de Adragao. Se realizó un seguimiento hasta el 1/1/2019, la muerte o el trasplante. De los 30 pacientes incluidos, 7 (23.3%) fallecieron por causa cardiovascular. El tiempo de seguimiento fue de 44.1 ± 30.4 (rango = 1.4-112) meses. El score de Adragao fue la única variable predictiva de muerte cardiovascular a largo plazo (área bajo la curva = 0.82; IC95% = 0.64-0.94; p<0.001). El mejor punto de corte fue de 5 (sensibili dad = 85.7%; especificidad = 78.3%). Además, fue un factor de riesgo independiente de muerte cardiovascular ajustado por edad, diabetes mellitus, enfermedad coronaria, calcificaciones aorticas, tiempo de permanencia en diálisis y tiempo de seguimiento (OR ajustado = 1.77; IC95% = 1.06-2.96; p = 0.028). Las calcificaciones vasculares cuantificadas a partir del score de Adragao fueron el único predictor independiente de mortalidad cardiovascular a largo plazo. Este score representa una herramienta simple, útil y superior a los biomarcadores del MOM.

Prediction of gestational diabetes mellitus in the first trimester: comparison of maternal fetuin-A, N-terminal proatrial natriuretic peptide, high-sensitivity C-reactive protein, and fasting glucose levels

ABSTRACT Objective We investigated the utility of maternal fetuin-A, N-terminal proatrial natriuretic peptide (pro-ANP), high-sensitivity C-reactive protein (hs-CRP), and fasting glucose levels at 11-14 gestation weeks for predicting pregnancies complicated by gestational diabetes mellitus (GDM). Subjects and methods This prospective cohort study included 327 low-risk pregnant women who completed antenatal follow-up at a tertiary research hospital between January and April 2014. Maternal blood samples were collected between 11-14 gestational weeks in the first trimester of pregnancy and then stored at -80 °C until further analyses. During follow-up, 29 (8.8%) women developed GDM. The study population was compared 1:2 with age- and body mass index-matched pregnant women who did not develop GDM (n = 59). Fasting plasma glucose (FPG) levels and serum fetuin-A, pro-ANP, and hs-CRP levels were measured using automated immunoassay systems. Results There was a significant negative correlation between fetuin-A and hs-CRP (CC = -0.21, p = 0.047) and a positive correlation between FPG and hs-CRP (CC = 0.251, p = 0.018). The areas under the receiver operating characteristic curve for diagnosing GDM were 0.337 (p = 0.013), 0.702 (p = 0.002), and 0.738 (p < 0.001) for fetuin-A, hs-CRP, and FPG, respectively. The optimal cut-off values were > 4.65, < 166, and > 88.5 mg/dL for maternal hs-CRP, fetuin-A, and FPG, respectively. Conclusion Reduced fetuin-A, elevated hs-CRP, and FPG levels in women in the first trimester can be used for the early detection of GDM. Further research is needed before accepting these biomarkers as valid screening tests for GDM.

Study on the Correlation of Fetuin A Gene Polymorphism and Lower Extremity Atherosclerosis with Type 2 Diabetes of Yi Nationality in Yunnan Province / 医学研究杂志

Objective To investigate the Allele and genotype frequency distribution of four single nucleotide polymorphisms(SNPs)sites (rs4917,rs491 8,rs1071592,rs2248690) in Fetuin A gene with type 2 diabetes and type 2 diabetes complicated by atherosclerosis of lower limb arteries(ALLA) in Yi Nationality of Chuxiong,and evaluated for association of Fetuin A polymorphisms with ALLA in type 2 diabetes.Methods Four SNPs in Fetuin A were genotyped in One hundred twenty normal controls,sixty one T2DM cases and sixty seven ALLA in type 2 diabetes by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) and allelic specific primer-polymerase chain reaction(ASP-PCR).Results The CC genotype and Allele C of rs1071592 in normal controls was lower than those which ALLA in type 2 diabetes(P ＜ 0.01),and there were no significant differences in frequency of genotype and allele distributions in the polymorphism analysis of rs4917 (C/T),rs4918 (C/G),rs2248690 (A/T) in these three groups (P ＞ 0.05).Logistic regression analysis showed:the CC genotype of rs1071592 in Fetuin A were nominally associated with atherosclerosis of lower limb arteries of T2DM.Conclusion There existed polymorphism of4917(C/T),rs4918(C/G),rs2248690(A/T),rs1071592(C/A) of Fetuin A in Yi nationality of chuxiong.The CC genotype of rs1071592 might be genetic risk factors of type 2 diabetes complicated by ALLA.

Associations of serum fetuin-A and oxidative stress parameters with polycystic ovary syndrome / 대한생식의학회지

OBJECTIVE: The aim of this study was to compare serum fetuin-A levels and oxidative stress markers, as indicators of insulin resistance, in women with polycystic ovary syndrome (PCOS) and in healthy controls. METHODS: This prospective case-control study included 46 patients with PCOS and 48 age- and body mass index–matched control women. Levels of serum hormones, fetuin-A, and oxidative stress markers were measured in blood samples taken during the early follicular period from each participant. RESULTS: Follicle-stimulating hormone (FSH), luteinising hormone (LH), total testosterone levels, and the LH/FSH ratio were found to be significantly higher in women with PCOS than in controls. Serum total antioxidant status, total oxidant status, and oxidative stress index parameters all indicated significantly higher levels of oxidative stress in PCOS patients than in controls. Serum fetuin-A levels, which were analyzed as an indicator of insulin resistance, were higher in the PCOS group than in the control group (210.26±65.06 µg/mL and 182.68±51.20 µg/mL, respectively; p=0.024). CONCLUSION: The data obtained from the present study suggest that higher levels of both serum fetuin-A and oxidative stress markers might be related with PCOS.

Study on the Relationship of Carotid Intimal-Medial Wall Thickness and the Expression of IL-6 and Fetuin-A in the Serum of Two Type Diabetes / 现代检验医学杂志

Objective To investigate the relationship of carotid intimal-medial wall thickness(IMT) and the expression of IL-6 and Fetuin-A in two type diabetes.Methods 80 patients with two type diabetes were chosen,and 60 cases healthypeople of examination for the control group.The levels of IL-6 and Fetuin-A were measured,and measured the intimal-medial thickness (IMT) of internal carotid artery by carotid duplex ultrasonography scanning simultaneously.Results The level of IL-6 was significantly higher in two type diabetes than those in control group,and the level of Fetuin-A was declind (t=8.34 ～15.65,all P＜0.05).IL-6 level in normal IMT (A group,20 cases) was 2.24±0.21 pg/L,Fetuin level was 5.41±0.32 ng/ ml.IL-6 level in abnormal IMT (B group,18 cases) was 3.44±0.18 mm,and Fetuin level was 3.86±0.42 ng/ml.Relatively,IL-6 level in IMT with plaque (C group,22 cases) was 4.95-±-0.31 ng/ml,Fetuin-A level was 2.41±0.32 ng/ml.IL-6 level in lumen narrow (D group,20 cases) was 5.35±0.31 ng/ml,and Fetuin-A level was 2.02 ± 0.08 ng/ml.There were obvious differences for four groups to detect IL-6 was Fetuin-A levels (F=8.69 ～ 11.02,all P＜ 0.05).The level of IL-6 were rised little by little from A group to D group.There were obvious differences for comparison among groups (t=5.32～9.01,all P＜0.05).The level of Fetuin-A were declined little by little from A group to D group,there were obvious differnce for comparison among groups (t=6.14～11.53,all P＜0.05).Conclusion There was a close correlation between IL-6,Fetuin-A level and carotid intimal-medial wall thickness(IMT) in two type diabetes.To detection IL-6 and Fetuin-A levels is a target to distinguish two type diabetes whether or not with atherosclerosis.

Association between Healthy Eating Index-2010 and Fetuin-A Levels in Patients with Type 2 Diabetes: a Case-Control Study

The Healthy Eating Index-2010 (HEI-2010) assesses compliance with the 2010 Dietary Guidelines for Americans. Studies suggest that adherence to the HEI-2010 is related to lower the risk of type 2 diabetes (T2D). Fetuin-A, a novel biomarker for T2D, may play a linking role in the inverse association between HEI-2010 and T2D. Thus, a case-control analysis involving 107 patients with T2D and107 healthy subjects was conducted to determine the association between HEI-2010 and serum fetuin-A levels. The results of simple regression analysis showed that fetuin-A levels were positively associated with full name of body mass index (BMI) (p < 0.001), waist circumference (WC) (p < 0.001), fasting blood glucose (FBG) (p < 0.001), triglycerides (TG) (p = 0.003), gamma-glutamyl transferase (GGT) (p < 0.001), and homeostasis model assessment of insulin resistance (HOMA-IR) (p =0.001) and negatively associated with physical activity (PA) (p < 0.001), high-density lipoprotein (HDL) (p = 0.022), and HEI-2010 (p < 0.001) in all subjects. After controlling for confounders, the inverse association between fetuin-A and HEI-2010 remained significant in the subjects with T2D (β = −0.386; p < 0.001), 107 healthy controls (β = −0.237; p = 0.028), and all subjects (β = −0.298; p < 0.001). In conclusion, the present results suggested that higher quality diet assessed by HEI-2010 associates with lower serum fetuin-A levels in people with and without T2D. More studies are needed to confirm these findings.

Association between Healthy Eating Index-2010 and Fetuin-A Levels in Patients with Type 2 Diabetes: a Case-Control Study

The Healthy Eating Index-2010 (HEI-2010) assesses compliance with the 2010 Dietary Guidelines for Americans. Studies suggest that adherence to the HEI-2010 is related to lower the risk of type 2 diabetes (T2D). Fetuin-A, a novel biomarker for T2D, may play a linking role in the inverse association between HEI-2010 and T2D. Thus, a case-control analysis involving 107 patients with T2D and107 healthy subjects was conducted to determine the association between HEI-2010 and serum fetuin-A levels. The results of simple regression analysis showed that fetuin-A levels were positively associated with full name of body mass index (BMI) (p < 0.001), waist circumference (WC) (p < 0.001), fasting blood glucose (FBG) (p < 0.001), triglycerides (TG) (p = 0.003), gamma-glutamyl transferase (GGT) (p < 0.001), and homeostasis model assessment of insulin resistance (HOMA-IR) (p =0.001) and negatively associated with physical activity (PA) (p < 0.001), high-density lipoprotein (HDL) (p = 0.022), and HEI-2010 (p < 0.001) in all subjects. After controlling for confounders, the inverse association between fetuin-A and HEI-2010 remained significant in the subjects with T2D (β = −0.386; p < 0.001), 107 healthy controls (β = −0.237; p = 0.028), and all subjects (β = −0.298; p < 0.001). In conclusion, the present results suggested that higher quality diet assessed by HEI-2010 associates with lower serum fetuin-A levels in people with and without T2D. More studies are needed to confirm these findings.

Fetuin A: A Newer Marker for Pre Diabetes.

Objective: To evaluate the role of Fetuin A levels in predicting glycemic outcome in individuals with impaired fasting glucose. Research Design and Methods: A total of 742 young individuals were recruited for the study out of which 177 had impaired fasting glucose, 468 had normoglycemia and 97 individuals with diabetes. These individuals were offsprings of diabetics (either mother or father or both) and were siblings amongst themselves belonging to age group of 18-35 years. Various biochemical investigations such as fasting plasma glucose, glycosylated Hb, serum insulin, C-peptide and Fetuin A were carried out. People with impaired fasting glucose were followed and analyzed according to glycemic outcome and quartile of Fetuin A level. Results: A total of 66 individuals with prediabetes reverted back to normal, 28 progressed to diabetes and 83 remained with prediabetes over a mean±S.D follow up of 24±4.1 months. People in the highest quartile of fetuin A had the highest Insulin, Insulin Resistance, Increased loss of beta cell activity, decreased sensitivity to insulin and a higher rate of progression to diabetes (relative risk 11.96, 95% CI 5.9 to 24.01, p<0.001) and a significantly lower rate of reversion to normoglycemia (relative risk 5.62, 95% CI 3.16 to 9.9, p<0.001) than those in other Fetuin A quartiles. fetuin A correlated positively with Insulin (r= +0.289, p<0.001), C-peptide (r=+ 0.177, p<0.001), %β cell function(r= -0.368, p<0.001), insulin resistance (r= +0.436, p<0.001) and glycosylated Hb (r=+0.958, p<0.05) and negatively with % sensitivity to insulin( r= -0.287, p<0.001). Cox regression analysis showed that baseline fetuin A, insulin levels and fasting glucose levels were predictive of reversion to normoglycemia. Conclusions: Increased fetuin A levels had an adverse impact on glycemic outcomes thus suggesting that fasting plasma glucose and Fetuin A can be used as a tool to determine the susceptibility of an individual to develop pre-diabetes and thus diabetes mellitus.

Correlation of fetuin-a gene RS1071592 and RS2593813 single nucleotide polymorphisms with polycystic ovary syndrome / 解放军医学杂志

Objective: To investigate the relations of Fetuin-A gene rs1071592 and rs2593813 single nucleotide polymorphisms (SNPs) with the affect ability to polycystic ovary syndrome (PCOS) and its endocrine and metabolic characteristics in Chongqing Han population. Methods: A case-control study was performed in Chinese Han subjects. The clinical data of 156 cases of normal control and 147 cases of PCOS patients were collected, and their blood glucose, lipids, sex hormone and other biochemical indexes were determined, the SNPs of rs1071592 and rs2593813 were genotyped by TaqMan SNP Genotyping Assay. Hyperinsulinemic-euglycemic clamp was performed in 147 PCOS women and 20 controls. The relative risk of developing PCOS in women with rs1071592 genotype was assessed using a binary logistic regression analysis. Results: The distribution frequency of Fetuin-A gene homozygous rs1071592 AA genotype and A allele was significantly increased in PCOS patients than in controls (Pc0.05). Binary logistic regression analysis showed that the risk of developing PCOS was 4.93 times high in women with AA genotype of rs1071592 (OR=4.933, 95%CI 1.593-15.278, P0.05). Conclusion: People with SNPs variants of rs1071592 in Fetuin-A gene may have an increased genetic susceptibility to PCOS. However, there won't be significant relationship between SNP of rs2593813 at Fetuin-A gene and PCOS.

Association of fetuin A, left ventricular function and residual renal function in peritoneal dialysis patients / 中华肾脏病杂志

Objective To investigate the relationship between fetuin A and left ventricular function and their influences on residual renal function(RRF) in peritoneal dialysis patients.Method Eighty patients recently initiating peritoneal dialysis were enrolled into this study and were divided into high fetuin A group and low fetuin A group accordin to the value of serum fetuin A concentration.Hemoglobin,high sensitive C reactive protein(hsCRP),calcium,phosphorus,albumin,lipoproteins and left ventricular myocardial performance index(LV-MPI) were examined.All these patients were followed up for 12 months,to discover the parameters' differences between two groups and to investigate the association between fetuin A and left ventricular function and RRF.Results At the beginning of the study,there was no difference of hsCRP,calcium,phosphorus,albumin,lipoproteins and LV-MPI,estimated glomerular filtration rate (eGFR) between two groups;After 12 months follow-up,MPI was obviously shorter (P ＜ 0.05) and RRF was obviously higher (P ＜ 0.05) in high fetuin A group than thosein low fetuin A group.Compared with the beginning of the study,LV-MPI was significantly increased and eGFR was significantly decreased after 12 months follow-up (both P ＜ 0.05) in low fetuin A group,but no obviously change of LV-MPI or eGFR was found in high fetuin A group after followup.Pearson correlation analysis discovered an obvious negative correlation between fetuin A and MPI (r=-0.680,P ＜ 0.01).Multiple regression analysis indicated that eGFR had positive correlation with fetuin A (B=0.058,t=3.679,P＜ 0.01) and negative correlations with MPI (B=-0.511,t=-2.903,P=0.007),age(B=-0.144,t=-4.013,P＜0.01).Diabetes was risk factor to loss of RRF (B=-2.031,t=-2.759,P ＜ 0.05).Conclusion Fetuin A has very close relationship with left ventricular function.Decreased serum fetuin A level and decreased left ventricular function are risk factors to the loss of the RRF in ERSD patients.

Comparison of pre- and post-levothyroxine high-sensitivity c-reactive protein and fetuin-a levels in subclinical hypothyroidism

OBJECTIVE: The objective of this trial was to determine the levels of inflammatory markers, high-sensitivity C-reactive protein and fetuin-A pre- and post-levothyroxine treatment in cases of subclinical hypothyroidism. MATERIALS AND METHODS: A total of 32 patients with a diagnosis of subclinical hypothyroidism and a control group of 30 healthy individuals were tested for high-sensitivity C-reactive protein and fetuin-A, followed by the administration of 50 µg of levothyroxine in the patient group for 3 months. During the post-treatment stage, high-sensitivity C-reactive protein and fetuin-A levels in the patient group were re-assessed and compared with pre-treatment values. RESULTS: Pre-treatment levels of both high-sensitivity C-reactive protein and fetuin-A were observed to be higher in the patient group than in the control group. The decrease in high-sensitivity C-reactive protein levels during the post-treatment stage was not statistically significant. However, the decrease observed in post-treatment fetuin-A levels was found to be statistically significant. CONCLUSION: The decrease in fetuin-A levels in subclinical hypothyroidism cases indicates that levothyroxine treatment exerts anti-inflammatory and anti-apoptotic effects. Although the decrease in high-sensitivity C-reactive protein levels was statistically non-significant, it is predicted to reach significance with sustained treatment. .

Serum Fetuin A, hs-CRP and Homocysteine as Biochemical Markers of Cardiovascular Complications in Chronic Dialysis Patients.

Introduction: Chronic kidney disease (CKD) patients are considered a high risk group of cardiovascular disease in which vascular calcifi cation plays central role. A pivotal role in the inhibition of calcifi cation is played by fetuin-A. Th e measurement of infl ammatory markers such as high sensitivity C-reactive protein (hs-CRP) and homocysteine which promotes atherosclerosis is helpful in predicting cardiovascular disease in ESRD patients on regular dialysis. Material and Method: Th e study included 40 adult CKD patients divided into 30 ESRD patients on conventional hemodialysis, 15 with CVD and 15 without CVD, as well as 10 CKD patients on conservative treatment. Ten healthy subjects served as a control group. Enzyme-linked immunosorbent assays were used for fetuin-A, hs-CRP and homocysteine. Results: ESRD patients showed a signifi cant increase in serum hs-CRP, homocysteine and decrease in fetuin-A compared to control group. In addition, ESRD patients with CVD and without CVD showed a signifi cant increase in hs-CRP, homocysteine and only those with CVD had signifi cantly decreased fetuin-A in relation to CKD patients. Th e study revealed increased levels of hs-CRP and decrease in fetuin-A in ESRD patients with CVD compared to ESRD patients without CVD. Fetuin-A showed a negative correlation with hs-CRP and homocysteine in ESRD patients with and without CVD. Conclusion: Th e combined use of hs-CRP at a cutoff of (10 mg/dL) with either fetuin-A at a cutoff value of (0.26 g/L) or alternatively with homocysteine at a cutoff value of (48.23 μmol/L) proved to be eff ective for discrimination of CVD patients from other ESRD or CKD patients.

Hepatokines as a Link between Obesity and Cardiovascular Diseases

Non-alcoholic fatty liver disease, which is considered a hepatic manifestation of metabolic syndrome, independently increases the risks of developing cardiovascular disease (CVD) and type 2 diabetes mellitus. Recent emerging evidence suggests that a group of predominantly liver-derived proteins called hepatokines directly affect the progression of atherosclerosis by modulating endothelial dysfunction and infiltration of inflammatory cells into vessel walls. Here, we summarize the role of the representative hepatokines fibroblast growth factor 21, fetuin-A, and selenoprotein P in the progression of CVD.

Exendin-4 Inhibits the Expression of SEPP1 and Fetuin-A via Improvement of Palmitic Acid-Induced Endoplasmic Reticulum Stress by AMPK

BACKGROUND: Selenoprotein P (SEPP1) and fetuin-A, both circulating liver-derived glycoproteins, are novel biomarkers for insulin resistance and nonalcoholic fatty liver disease. However, the effect of exendin-4 (Ex-4), a glucagon-like peptide-1 receptor agonist, on the expression of hepatokines, SEPP1, and fetuin-A, is unknown. METHODS: The human hepatoma cell line HepG2 was treated with palmitic acid (PA; 0.4 mM) and tunicamycin (tuni; 2ug/ml) with or without exendin-4 (100 nM) for 24 hours. The change in expression of PA-induced SEPP1, fetuin-A, and endoplasmic reticulum (ER) stress markers by exendin-4 treatment were evaluated using quantitative real-time reverse transcription polymerase chain reaction and Western blotting. Transfection of cells with AMP-activated protein kinase (AMPK) small interfering RNA (siRNA) was performed to establish the effect of exendin-4-mediated AMPK in the regulation of SEPP1 and fetuin-A expression. RESULTS: Exendin-4 reduced the expression of SEPP1, fetuin-A, and ER stress markers including PKR-like ER kinase, inositol-requiring kinase 1alpha, activating transcription factor 6, and C/EBP homologous protein in HepG2 cells. Exendin-4 also reduced the expression of SEPP1 and fetuin-A in cells treated with tunicamycin, an ER stress inducer. In cells treated with the AMPK activator 5-aminoidazole-4-carboxamide ribonucleotide (AICAR), the expression of hepatic SEPP1 and fetuin-A were negatively related by AMPK, which is the target of exendin-4. In addition, exendin-4 treatment did not decrease SEPP1 and fetuin-A expression in cells transfected with AMPK siRNA. CONCLUSION: These data suggest that exendin-4 can attenuate the expression of hepatic SEPP1 and fetuin-A via improvement of PA-induced ER stress by AMPK.

Fetuin-A is related to syndesmophytes in patients with ankylosing spondylitis: a case control study

OBJECTIVES: New bone formation is one of the hallmark characteristics of ankylosing spondylitis, which is thereby associated with syndesmophytes. Fetuin-A is a molecule that is abundantly found in calcified tissues and it shows high affinity for calcium phosphate minerals and related compounds. Considering the role of fetuin-A in the regulation of calcified matrix metabolism, we compared the fetuin-A levels in ankylosing spondylitis patients with syndesmophytes with those in patients without syndesmophytes and in healthy controls. We also studied other biomarkers that are thought to be related to syndesmophytes. METHODS: Ninety-four patients (49 patients without syndesmophytes, 67.3% male, 40.7±8.7 years; 45 patients with syndesmophytes, 71.1% M, 43.9±9.9 years) and 68 healthy controls (44.2±10.6 years and 70.6% male) were included in this study. Syndesmophytes were assessed on the lateral radiographs of the cervical and lumbar spine. The serum levels of fetuin-A, dickkopf-1, sclerostin, IL-6, high-sensitivity C-reactive protein and bone morphogenetic protein-7 were measured with an enzyme-linked immunosorbent assay. RESULTS: Patients with syndesmophytes had significantly higher levels of fetuin-A compared with patients without syndesmophytes and controls (1.16±0.13, 1.05±0.09 and 1.08±0.13 mg/ml, respectively). However, fetuin-A was not different between the patients without syndesmophytes and controls. Bone morphogenetic protein-7 was significantly lower; dickkopf-1 was significantly higher in patients with ankylosing spondylitis compared with controls. The sclerostin concentrations were not different between the groups. In regression analysis, fetuin-A was an independent, significant predictor of syndesmophytes. CONCLUSION: Our results suggest that fetuin-A may a role in the pathogenesis of bony proliferation in ankylosing spondylitis. .

Actualización en la fisiopatología de la preeclampsia: update

La preeclampsia constituye una de las complicaciones más frecuentes y a la vez más serias de la gestación y contribuye de manera significativa a la mortalidad materna y perinatal. No obstante los avances en el estudio de la preeclampsia, aún no está del todo esclarecido su mecanismo fisiopatológico. En este capítulo, intentamos revisar nuevas teorías propuestas acerca de su fisiopatología. Los aspectos genéticos y angiogénicos serán revisados en otros capítulos de este simposio.

Preeclampsia is one of the most frequent and serious disorders of pregnancy. It is a significant contributor of maternal and perinatal mortality worldwide. An important amount of research has been devoted in the research of preeclampsia in the recent years; nonetheless, its pathophysiology is yet to be completely understood. In this review, we will discuss new proposed theories on the pathophysiology of preeclampsia. Genetic and angiogenic aspects of preeclampsia will be reviewed elsewhere in this issue.