Evaluation of ADAM-12 as a Diagnostic Biomarker of Ectopic Pregnancy in Women with a Pregnancy of Unknown Location

Background

Ectopic pregnancy (EP) remains the most life-threatening acute condition in modern gynaecology. It remains difficult to diagnose early and accurately. Women often present at emergency departments in early pregnancy with a ‘pregnancy of unknown location’ (PUL) and diagnosis/exclusion of EP is challenging due to a lack of reliable biomarkers. Recent studies suggest that serum levels of a disintegrin and metalloprotease protein-12 (ADAM-12) can be used differentiate EP from viable intrauterine pregnancy (VIUP). Here we describe a prospective study evaluating the performance of ADAM-12 in differentiating EP from the full spectrum of alternative PUL outcomes in an independent patient cohort.

Methodology/Principal Findings

Sera were collected from 120 patients at their first clinical presentation with a PUL and assayed for ADAM-12 by ELISA. Patients were categorized according to final pregnancy outcomes. Serum ADAM-12 concentrations were increased in women with histologically-confirmed EP (median 442 pg/mL; 25%–75% percentile 232–783 pg/mL) compared to women with VIUP (256 pg/mL; 168–442 pg/mL) or miscarriage (192 pg/mL; 133–476 pg/mL). Serum ADAM-12 did not differentiate histologically-confirmed EP from spontaneously resolving PUL (srPUL) (416 pg/mL; 154–608 pg/mL). The diagnostic potential of ADAM-12 was only significant when ‘ambiguous’ PUL outcomes were excluded from the analysis (AROC = 0.6633; P = 0.03901).

Conclusions/Significance

When measured in isolation, ADAM-12 levels had limited value as a diagnostic biomarker for EP in our patient cohort. The development of a reliable serum biomarker-based test for EP remains an ongoing challenge.     

Shotgun Proteomics Identifies Serum Fibronectin as a Candidate Diagnostic Biomarker for Inclusion in Future Multiplex Tests for Ectopic Pregnancy

Ectopic pregnancy (EP) is difficult to diagnose early and accurately. Women often present at emergency departments in early pregnancy with a ‘pregnancy of unknown location’ (PUL), and diagnosis and exclusion of EP is challenging due to a lack of reliable biomarkers. The objective of this study was to identify novel diagnostic biomarkers for EP. Shotgun proteomics, incorporating combinatorial-ligand library pre-fractionation, was used to interrogate pooled sera (n = 40) from women undergoing surgery for EP, termination of viable intrauterine pregnancy and management of non-viable intrauterine pregnancy. Western blot was used to validate results in individual sera. ELISAs were developed to interrogate sera from women with PUL (n = 120). Sera were collected at time of first symptomatic presentation and categorized according to pregnancy outcome. The main outcome measures were differences between groups and area under the receiver operating curve (ROC). Proteomics identified six biomarker candidates. Western blot detected significant differences in levels of two of these candidates. ELISA of sera from second cohort revealed that these differences were only significant for one of these candidates, fibronectin. ROC analysis of ability of fibronectin to discriminate EP from other pregnancy outcomes suggested that fibronectin has diagnostic potential (ROC 0.6439; 95% CI 0.5090 to 0.7788; P>0.05), becoming significant when ‘ambiguous’ medically managed PUL excluded from analysis (ROC 0.6538; 95% CI 0.5158 to 0.7918; P<0.05). Fibronectin may make a useful adjunct to future multiplex EP diagnostic tests.     

Macrophage Inhibitory Cytokine 1 Biomarker Serum Immunoassay in Combination with PSA Is a More Specific Diagnostic Tool for Detection of Prostate Cancer

Background

Prostate cancer (PCa) is the most common malignancy among men in the United States. Though highly sensitive, the often-used prostate-specific antigen (PSA) test has low specificity which leads to overdiagnosis and overtreatment of PCa. This paper presents results of a retrospective study that indicates that testing for macrophage inhibitory cytokine 1 (MIC-1) concentration along with the PSA assay could provide much improved specificity to the assay.

Methods

The MIC-1 serum level was determined by a novel p-Chip-based immunoassay run on 70 retrospective samples. The assay was configured on p-Chips, small integrated circuits (IC) capable of storing in their electronic memories a serial number to identify the molecular probe immobilized on its surface. The distribution of MIC-1 and pre-determined PSA concentrations were displayed in a 2D plot and the predictive power of the dual MIC-1/PSA assay was analyzed.

Results

MIC-1 concentration in serum was elevated in PCa patients (1.44 ng/ml) compared to normal and biopsy-negative individuals (0.93 ng/ml and 0.88 ng/ml, respectively). In addition, the MIC-1 level was correlated with the progression of PCa. The area under the receiver operator curve (AUC-ROC) was 0.81 providing an assay sensitivity of 83.3% and specificity of 60.7% by using a cutoff of 0.494 for the logistic regression value of MIC-1 and PSA. Another approach, by defining high-frequency PCa zones in a two-dimensional plot, resulted in assay sensitivity of 78.6% and specificity of 89.3%.

Conclusions

The analysis based on correlation of MIC-1 and PSA concentrations in serum with the patient PCa status improved the specificity of PCa diagnosis without compromising the high sensitivity of the PSA test alone and has potential for PCa prognosis for patient therapy strategies.     

Blood Cadmium Concentrations in Women with Ectopic Pregnancy

The purpose of this study is to investigate the relationship between the blood level of cadmium and the occurrence of ectopic pregnancy. Forty-one (41) case patients with ectopic pregnancy and 41 uncomplicated intrauterine pregnant patients as controls were recruited. The concentrations of cadmium (Cd) were measured from blood samples using atomic absorption spectrometry. The cases and controls were similar in age, body mass index, and smoking habits. The median blood level of Cd was 0.32 μg/l (interquartile range [IQR] 0.00–0.71) in the women with ectopic pregnancies and 0.34 μg/l (IQR 0.09–0.59) in the controls. There was no significant association between blood cadmium levels and ectopic pregnancy.     

Macrophage Inhibitory Cytokine-1 (MIC-1/GDF15) Gene Deletion Promotes Cancer Growth in TRAMP Prostate Cancer Prone Mice

The divergent TGF-β superfamily member, macrophage inhibitory cytokine-1 (MIC-1/GDF15), is overexpressed by most cancers, including prostate cancer (PCa). Whilst its circulating levels are linked to cancer outcome, the role MIC-1/GDF15 plays in cancer development and progression is incompletely understood. To investigate its effect on PCa development and spread, we have used TRAMP prostate cancer prone mice bearing a germline deletion of MIC-1/GDF15 (TRAMP^MIC-/-). On average TRAMP^MIC-/- mice died about 5 weeks earlier and had larger prostatic tumors compared with TRAMP mice that were wild type for MIC-1/GDF15 (TRAMP^MIC+/+). Additionally, at the time of death or ethical end point, even when adjusted for lifespan, there were no significant differences in the number of mice with metastases between the TRAMP^MIC+/+ and TRAMP^MIC-/- groups. However, consistent with our previous data, more than twice as many TRAMP mice overexpressing MIC-1/GDF15 (TRAMP^fmsmic-1) had metastases than TRAMP^MIC+/+ mice (p<0.0001). We conclude that germ line gene deletion of MIC-1/GDF15 leads to increased local tumor growth resulting in decreased survival consistent with an overall protective role for MIC-1/GDF15 in early primary tumor development. However, in advancing disease, as we have previously noted, MIC-1/GDF15 overexpression may promote local invasion and metastatic spread.     

CB1 Expression Is Attenuated in Fallopian Tube and Decidua of Women with Ectopic Pregnancy

Background

Embryo retention in the Fallopian tube (FT) is thought to lead to ectopic pregnancy (EP), a considerable cause of morbidity. In mice, genetic/pharmacological silencing of cannabinoid receptor Cnr1, encoding CB1, causes retention of embryos in the oviduct. The role of the endocannabinoids in tubal implantation in humans is not known.

Methods and Findings

Timed FT biopsies (n = 18) were collected from women undergoing gynecological procedures for benign conditions. Endometrial biopsies and whole blood were collected from women undergoing surgery for EP (n = 11); management of miscarriage (n = 6), and termination of pregnancy (n = 8). Using RT-PCR and immunohistochemistry, CB1 mRNA and protein expression levels/patterns were examined in FT and endometrial biopsies. The distribution of two polymorphisms of CNR1 was examined by TaqMan analysis of genomic DNA from the whole blood samples. In normal FT, CB1 mRNA was higher in luteal compared to follicular-phase (p<0.05). CB1 protein was located in smooth muscle of the wall and of endothelial vessels, and luminal epithelium of FT. In FT from women with EP, CB1 mRNA expression was low. CB1 mRNA expression was also significantly lower (p<0.05) in endometrium of women with EP compared to intrauterine pregnancies (IUP). Although of 1359G/A (rs1049353) polymorphisms of CNR1 gene suggests differential distribution of genotypes between the small, available cohorts of women with EP and those with IUP, results were not statistically significant.

Conclusions

CB1 mRNA shows temporal variation in expression in human FT, likely regulated by progesterone. CB1 mRNA is expressed in low levels in both the FT and endometrium of women with EP. We propose that aberrant endocannabinoid-signaling in human FT leads to EP. Furthermore, our finding of reduced mRNA expression along with a possible association between polymorphism genotypes of the CNR1 gene and EP, suggests a possible genetic predisposition to EP that warrants replication in a larger sample pool.     

Maternal Serum Disintegrin and Metalloprotease Protein-12 in Early Pregnancy as a Potential Marker of Adverse Pregnancy Outcomes

Objectives

The aim of this study was to determine whether the concentration of disintegrin and metalloprotease protein12 (ADAM12) in first trimester maternal serum can be used as a marker for first-trimester complete spontaneous abortions, missed abortions, ectopic pregnancies and hydatidiform moles.

Methods

The maternal serum concentrations of ADAM12 were measured in the range of 5–9⁺⁶ weeks of gestation using an automated AutoDelfia immunoassay platform in 9 cases of complete spontaneous abortion, 27 cases of missed abortions, 56 cases of ectopic pregnancies, 12 cases of hydatidiform moles, and 100 controls. Logistic regression analysis was used to determine significant factors for predicting adverse pregnancy outcomes in early pregnancy. Screening performance was assessed using receiver operating characteristic curves.

Results

Two hundred and four women were enrolled in the study. In the control group, the level of ADAM12 increased with gestational age. The median ADAM12 levels in the spontaneous abortion (0.430 MoM), ectopic pregnancy (0.460 MoM) and hydatidiform mole (0.037 MoM) groups were lower than that in the control group, while the median ADAM12 level in the missed abortion group (1.062 MoM) was not significant from the controls (1.002 MoM). Logistic regression analysis demonstrated that the level of ADAM12 in maternal serum facilitated the detection of ectopic pregnancies (OR = 0.909; 95% CI = 0.841∼0.982) and complete spontaneous abortion (OR = 0.863; 95% CI = 0.787∼0.946).

Conclusions

In complete spontaneous abortion and ectopic pregnancy, ADAM12 maintained at low levels in early pregnancies, and there were significant differences compared to normal pregnancies. ADAM12 is a promising marker for the diagnosis of complete spontaneous abortion and ectopic pregnancy in symptomatic women, and under certain conditions, ADAM12 can diagnose ectopic pregnancy and spontaneous abortion before an ultrasonographic detection of the conditions.     

Macrophage Inhibitory Cytokine-1 (MIC-1/GDF15) Slows Cancer Development but Increases Metastases in TRAMP Prostate Cancer Prone Mice

Macrophage inhibitory cytokine-1 (MIC-1/GDF15), a divergent member of the TGF-β superfamily, is over-expressed by many common cancers including those of the prostate (PCa) and its expression is linked to cancer outcome. We have evaluated the effect of MIC-1/GDF15 overexpression on PCa development and spread in the TRAMP transgenic model of spontaneous prostate cancer. TRAMP mice were crossed with MIC-1/GDF15 overexpressing mice (MIC-1(fms)) to produce syngeneic TRAMP(fmsmic-1) mice. Survival rate, prostate tumor size, histopathological grades and extent of distant organ metastases were compared. Metastasis of TC1-T5, an androgen independent TRAMP cell line that lacks MIC-1/GDF15 expression, was compared by injecting intravenously into MIC-1(fms) and syngeneic C57BL/6 mice. Whilst TRAMP(fmsmic-1) survived on average 7.4 weeks longer, had significantly smaller genitourinary (GU) tumors and lower PCa histopathological grades than TRAMP mice, more of these mice developed distant organ metastases. Additionally, a higher number of TC1-T5 lung tumor colonies were observed in MIC-1(fms) mice than syngeneic WT C57BL/6 mice. Our studies strongly suggest that MIC-1/GDF15 has complex actions on tumor behavior: it limits local tumor growth but may with advancing disease, promote metastases. As MIC-1/GDF15 is induced by all cancer treatments and metastasis is the major cause of cancer treatment failure and cancer deaths, these results, if applicable to humans, may have a direct impact on patient care.     

Copeptin as a Serum Biomarker of Febrile Seizures

Background and Objectives

Accurate diagnosis of febrile seizures in children presenting after paroxysmal episodes associated with fever, is hampered by the lack of objective postictal biomarkers. The aim of our study was to investigate whether FS are associated with increased levels of serum copeptin, a robust marker of arginine vasopressin secretion.

Methods

This was a prospective emergency-setting cross-sectional study of 161 children between six months and five years of age. Of these, 83 were diagnosed with febrile seizures, 69 had a febrile infection without seizures and nine had epileptic seizures not triggered by infection. Serum copeptin and prolactin levels were measured in addition to standard clinical, neurophysiological, and laboratory assessment. Clinical Trial Registration: NCT01884766.

Results

Circulating copeptin was significantly higher in children with febrile seizures (median [interquartile range] 18.9 pmol/L [8.5-36.6]) compared to febrile controls (5.6 pmol/L [4.1-9.4]; p <0.001), with no differences between febrile and epileptic seizures (21.4 pmol/L [16.1-46.6]; p = 0.728). In a multivariable regression model, seizures were the major determinant of serum copeptin (beta 0.509; p <0.001), independently of clinical and baseline laboratory indices. The area under the receiver operating curve for copeptin was 0.824 (95% CI 0.753-0.881), significantly higher compared to prolactin (0.667 [0.585-0.742]; p <0.001). The diagnostic accuracy of copeptin increased with decreasing time elapsed since the convulsive event (at 120 min: 0.879 [0.806-0.932] and at <60 min: 0.975 [0.913-0.997]).

Conclusions

Circulating copeptin has high diagnostic accuracy in febrile seizures and may be a useful adjunct for accurately diagnosing postictal states in the emergency setting.     

Maternal Serum C-Reactive Protein in Women with Preterm Prelabor Rupture of Membranes

Objective

This study evaluated maternal C-reactive protein (CRP) as a predictor of microbial invasion of the amniotic cavity (MIAC) and histological chorioamnionitis (HCA) in women with preterm prelabor rupture of the membranes (PPROM) before and after 32 weeks of gestation.

Methods

This study was a prospective observational cohort study of 386 women. Maternal serum CRP concentrations were evaluated, and amniotic fluid samples were obtained via transabdominal amniocentesis at the time of admission. Placentas underwent histopathological examination after delivery. MIAC was defined based on a positive PCR for Ureaplasma species, Mycoplasma hominis and Chlamydia trachomatis and/or positive 16S rRNA gene amplification. HCA was defined based on the Salafia classification.

Results

Maternal CRP was significantly higher in women with MIAC and HCA (median 9.0 mg/l) than in women with HCA alone (median 6.9 mg/l), MIAC alone (median 7.4 mg/l) and without MIAC or HCA (median 4.5 mg/l) (p<0.0001). CRP was a weak predictor of the occurrence of MIAC and HCA before and after 32 weeks of gestation. Only the 95^th percentile of CRP and PPROM before 32 weeks exhibited a false-positive rate of 1%, a positive predictive value of 90% and a positive likelihood ratio of 13.2 to predict MIAC and HCA. However, the low sensitivity of 15% limits the clinical utility of this detection.

Conclusion

CRP is a poor predictor of the occurrence of MIAC and HCA, even at early gestational ages.     

Serum Thiols as a Biomarker of Disease Activity in Lupus Nephritis

Lupus Nephritis (LN) develops in more than half of the Systemic Lupus Erythematous (SLE) patients. However, lack of reliable, specific biomarkers for LN hampers clinical management of patients and impedes development of new therapeutics. The goal of this study was to investigate whether oxidative stress biomarkers in patients with SLE is predictive of renal pathology. Serum biochemical and oxidative stress markers were measured in patients with inactive lupus, active lupus with and without nephritis and compared to healthy control group. To assess the predictive performance of biomarkers, Receiver Operating Characteristic (ROC) curves were constructed and cut-offs were used to identify SLE patients with nephritis. We observed an increased oxidative stress response in all SLE patients compared to healthy controls. Among the several biomarkers tested, serum thiols had a significant inverse association with SLE Disease Activity Index (SLEDAI). Interestingly, thiols were able too aptly differentiate between SLE patients with and without renal pathology, and serum thiol levels were not affected by immunosuppressive drug therapy. The decreased thiols in SLE correlated significantly with serum creatinine and serum C3 levels. Further retrospective evaluation using serum creatinine or C3 levels in combination with thiol’s cutoff values from ROC analysis, we could positively predict chronicity of renal pathology in SLE patients. In summary, serum thiols emerge as an inexpensive and reliable indicator of LN, which may not only help in early identification of renal pathology but also aid in the therapeutic management of the disease, in developing countries with resource poor settings.     

Serum Diamine Oxidase as a Hemorrhagic Shock Biomarker in a Rabbit Model

Background

In prolonged hemorrhagic shock, reductions in intestinal mucosal blood perfusion lead to mucosal barrier damage and systemic inflammation. Gastrointestinal failure in critically ill patients has a poor prognosis, so early assessment of mucosal barrier injury in shock patients is clinically relevant. Unfortunately, there is no serum marker that can accurately assess intestinal ischemia-reperfusion injury.

Objective

The aim of this study was to assess if serum diamine oxidase levels can reflect intestinal mucosal injury subsequent to prolonged hemorrhagic shock.

Methods

Thirty New Zealand white rabbits were divided into three groups: a control group, a medium blood pressure (BP) group (exsanguinated to a shock BP of 50 to 41 mm Hg), and a low BP group (exsanguinated to a shock blood pressure of 40 to 31 mm Hg), in which the shock BP was sustained for 180 min prior to fluid resuscitation.

Results

The severity of hemorrhagic shock in the low BP group was significantly greater than that of the medium BP group according to the post-resuscitation BP, serum tumor necrosis factor (TNF)-α, and arterial lactate. Intestinal damage was significantly more severe in the low BP group according to Chiu’s scoring, claudin-1, intercellular adhesion molecule (ICAM)-1, and myeloperoxidase expression. Serum diamine oxidase was significantly increased in the low BP group compared to the medium BP and control groups and was negatively correlated with shock BP.

Conclusion

Serum diamine oxidase can be used as a serological marker in evaluating intestinal injury and shows promise as an indicator of hemorrhagic shock severity.     

Peptidomic Analysis of Maternal Serum to Identify Biomarker Candidates for Prenatal Diagnosis of Tetralogy of Fallot

Tetralogy of Fallot (TOF) is the most common form of cyanotic congenital heart disease. To identify endogenous peptides possibly involved in the progression of TOF, we performed comparative peptidomic profiling of maternal serum between normal fetuses and fetuses suffering from TOF. A total of 278 differentially expressed peptides, including 94 over‐expressed peptides and 184 under‐expressed peptides, originating from 227 protein precursors were identified by liquid chromatography/mass spectrometry (LC/MS) in maternal serum of fetuses with TOF compared to normal controls. Further, ingenuity pathway analysis (IPA) was used to identify putative roles for these peptides in cardiovascular development. Two peptides were derived from functional domains of proteins involved in heart development and associated with TOF; these may represent candidate bioactive peptides involved in TOF. These peptides may be related to the pathologic changes in the heart associated with TOF, and may be useful as novel biomarkers for prenatal diagnosis of TOF. J. Cell. Biochem. 119: 468–477, 2018. © 2017 Wiley Periodicals, Inc.     

Identification of Kininogen-1 as a Serum Biomarker for the Early Detection of Advanced Colorectal Adenoma and Colorectal Cancer

Background

Serum markers represent potential tools for the detection of colorectal cancer (CRC). The aim of this study was to obtain proteomic expression profiles and identify serum markers for the early detection of CRC.

Methods

Proteomic profiles of serum samples collected from 35 healthy volunteers, 35 patients with advanced colorectal adenoma (ACA), and 40 patients with CRC were compared using Clinprot technology. Using enzyme-linked immunosorbent assays (ELISAs), 366 sera samples were additionally analyzed, and immunohistochemistry studies of 400 tissues were used to verify the expression of kininogen-1 and its value in the early detection of CRC.

Results

Predicting models were established among the three groups, and kininogen-1 was identified as a potential marker for CRC using Clinprot technology. ELISAs also detected significantly higher serum kininogen-1 levels in ACA and CRC patients compared to controls (P<0.05). Furthermore, the area under the receiver operating characteristic curve (AUC) for serum kininogen-1 in the diagnosis of ACA was 0.635 (P = 0.003), and for serum carcinoembryonic antigen (CEA) was 0.453 (P = 0.358). The sensitivity, specificity, and accuracy of serum kininogen-1 for diagnosing Duke’s stage A and B CRC was 70.13%, 65.88%, and 67.90%, respectively, whereas serum CEA was 38.96%, 85.88%, and 63.58%, respectively. Moreover, immunohistochemistry showed that expression of kininogen-1 was significantly higher in CRC and ACA tissues than in normal mucosa (48.39% vs. 15.58% vs. 0%, P<0.05).

Conclusions

These results suggest that Clinprot technology provides a useful tool for the diagnosis of CRC, and kininogen-1 is a potential serum biomarker for the early detection of advanced colorectal adenoma and CRC.     

EEG Features in Women with a Complicated Pregnancy

Clinical and EEG spectral analysis was carried out in 14 pregnant women (five women at risk of preterm labor and four with miscarriage). It was shown that the baseline EEG pattern of women with the persistent threat of preterm labor was characterized by the high spectral power of the -rhythm and its predisposition to hypersynchronization. In the miscarriage group, virtually a complete absence of the -rhythm and the predominance of generalized both high-frequency and slow low-amplitude rhythms are noted in most pregnant women. The data obtained allow a risk group characterized by either a hypersynchronous unstable -rhythm or its absence to be identified among pregnant women.     

Maternal Serum Heme-Oxygenase-1 (HO-1) Concentrations in Early Pregnancy and Subsequent Risk of Gestational Diabetes Mellitus

Background

Heme oxygenase-1 (HO-1) concentrations have been recently reported to be elevated in impaired glucose tolerance and type 2 diabetes mellitus (T2DM). However, no study has examined the association between HO-1 concentrations and gestational diabetes mellitus (GDM).

Methods

In a case-control study, nested within a prospective cohort of pregnant women (186 GDM cases and 191 women who remained eu-glycemic through pregnancy), we assessed the association of maternal serum HO-1 concentrations, measured in samples collected at 16 weeks gestation, on average, with subsequent risk of GDM. Maternal serum HO-1 concentrations were determined using ELISA. We fitted multivariate logistic regression models to derive estimates of odds ratios (ORs) and 95% confidence intervals (CIs).

Results

Median serum HO-1 concentrations in early pregnancy were lower in women who subsequently developed GDM compared with those who did not (1.60 vs. 1.80 ng/mL, p-value = 0.002). After adjusting for maternal age, race, family history of T2DM and pre-pregnancy body mass index, women with HO-1≥3.05 ng/mL (highest decile) experienced a 74% reduction of GDM risk (95% CI; 0.09–0.77) compared with women whose concentrations were<1.23 ng/mL (lowest quartile).

Conclusion

Serum HO-1 concentrations were inversely associated with subsequent GDM risk. These findings underscore the role of oxidative stress in the pathogenesis of GDM. Additional studies are warranted to confirm the clinical utility of serum HO-1 in diagnosis of GDM, particularly in the early pregnancy.     

Serum Retinol-Binding Protein 4 as a Marker for Cardiovascular Disease in Women

Background

Elevated serum level of retinol-binding protein 4 (RBP4) has been associated with obesity-related co-morbidities including insulin resistance, dyslipidemia and hypertension.

Objectives

The present study examined the relationship between serum level of RBP4 and various risk factors related to cardiovascular disease (CVD) in men and women.

Methods

284 subjects (139 males, 145 females), grouped into healthy (n = 60), obese diabetes (n = 60), non-obese diabetes (n = 60), obese non-diabetes (n = 60) and patients with CVD (n = 44), were assessed for anthropometric and biochemical parameters related to obesity, diabetes and CVD. In addition, serum levels of several adipokines, including fatty acid binding protein 4 (FABP4) and lipocalin 2 (LCN2) and RBP4 were measured using specific immunoassays.

Results

Serum RBP4 level correlated significantly with principal component derived from known risk factors of CVD (β = 0.20±0.06, P = 0.002). Significance of this correlation was limited to women (β = 0.20±0.06, P = 0.002) and it persisted even after adjusting for BMI (β = 0.19±0.06, P = 0.002). Overall (n = 284) serum RBP4 values significantly correlated with FABP4 (R = 0.19, p = 0.001). Serum FABP4 level of CVD subjects was significantly higher than healthy control (P = 0.001) and non-obese diabetes (P = 0.04) groups, but this difference was attributable to differences in BMI. Serum LCN2 level correlated well with RBP4 (R = 0.15, P = 0.008) and FABP4 (R = 0.36, P<0.001), but did not differ significantly between CVD and other groups.

Conclusions

Results of this study indicate a significant correlation between serum RBP4 and various established risk factors for CVD and suggest RBP4 may serve as an independent predictor of CVD in women.