血清chemerin 水平与代谢综合征患者合并冠心病的相关性研究

目的:旨在探讨血清脂肪因子chemerin水平与代谢综合征患者合并冠心病的相关性。方法:共纳入116名代谢综合征患者,将所有患者分为两组,合并冠心病组(CAD+,n=47)及未合并冠心病组(CAD-,n=69),使用酶联免疫吸附(ELISA)法测量每组血清的血清chemerin水平。结果:CAD+组患者的血清chemerin水平较CAD-组患者显著升高(129.83±29.18 vs 94.01±23.54 ng/mL;P<0.01),多元Logistic回归分析结果显示血清chemerin水平与代谢综合征患者合并冠心病存在独立相关性(优势比1.565,95%可信区间1.104-2.876;P<0.05)。结论:血清chemerin水平是代谢综合征患者合并冠心病的独立危险因子,血清chemerin可能是预测代谢综合征患者发生冠心病风险的重要的生物学标记物。     

血清网膜素-1与绝经后女性冠心病的相关性

目的：网膜素是最近发现的脂肪因子,肥胖或2型糖尿病（diabetesmellitus,DM）患者血清网膜素-1较正常者明显降低。本次研究主要为观察绝经后女性血清网膜素-1水平与冠心病的相关性。方法：选取我院心内科住院有心绞痛症状,并行冠脉造影的105例绝经后女性患者。依据冠脉造影结果分为冠心病组（67例）和对照组例（3）,常规收集临床资料,包括年龄、体重指数（bodvmassindex,BMI）、吸烟史、高血压病史、糖尿病史及血液生化和血脂指标;酶联免疫吸附剂测定（enzymelinkedimmunosorbentassay,ELISA）法检测血清网膜素-1浓度。结果：冠心痛组血清网膜素-1水平显著低于对照组（205．62±73．31vs401．64±146．79．P〈0．001）。单因素logistic回归分析示吸烟、高血压痛史、糖尿病史、高脂血症史、网膜素-1水平降低是冠心病组的独立危险因素（P〈0．05）。多因素logistic回归分析示血清网膜素-1水平降低是冠心病组的独立危险因素（P〈0．001）。结论：绝经后女性血清网膜素-1水平下降是冠心痛的独立危险因素,可能可成为绝经后女性冠心病的预测指标。     

Serum Metrnl is associated with the presence and severity of coronary artery disease

Meteorin‐like (Metrnl) is a novel adipokine that is highly expressed in white adipose tissue. Metrnl stimulates energy expenditure and improves glucose tolerance in rodents. However, whether Metrnl plays a role in coronary artery disease (CAD) remains to be elucidated. The present study aimed to investigate the association of serum Metrnl with CAD in Chinese patients. A total of 193 patients with CAD and 156 control subjects were enrolled in this study. Serum Metrnl concentration was measured by enzyme‐linked immunosorbent assay. Anthropometric phenotypes, fasting glucose, serum lipids, and inflammatory cytokines were measured. Serum Metrnl was lower in CAD patients when compared to those controls (132.41 vs 173.17 pg/mL, P < 0.001). Serum Metrnl was negatively correlated with metabolic parameters, including body mass index, total cholesterol, and low‐density lipoprotein cholesterol as well as inflammatory markers including high‐sensitivity C‐reactive protein, IL‐1β, and IL‐11 even after adjustment for potential confounding variables (P < 0.05). In multivariable logistic regression analyses, compared to those in the highest tertile of serum Metrnl levels, subjects in the lowest tertile had the highest risks for CAD (adjusted OR = 2.63, 95% CI = 1.46‐4.27, P = 0.001). After adjustment for potential confounding variables, serum Metrnl was also decreased as the number of stenosed vessels increased (P < 0.001). Furthermore, decreased Metrnl level was negatively correlated with the severity of CAD quantified by the Gensini score. This first case‐control study shows significant associations of serum Metrnl with the presence and severity of CAD, suggesting Metrnl might be a new promising therapeutic target for CAD.     

Association of secreted frizzled-related protein 4 (SFRP4) with type 2 diabetes in patients with stable coronary artery disease

Background

The interplay between the novel adipokine retinol-binding protein-4 (RBP4) and coronary artery disease (CAD) is still obscure. We investigated the relationship between RBP4 levels and the presence and severity of angiographically proven CAD and determined its possible role in acute myocardial infarction (AMI).

Methods

305 individuals with angiographically proven CAD (CAD-patients), were classified into 2 subgroups: 1) acute myocardial infarction (AMI, n = 141), and 2) stable angina (SA, n = 164). Ninety-one age- and sex-matched individuals without CAD, but with at least 2 classical cardiovascular risk factors, served as controls (non-CAD group). RBP4 serum levels were measured at hospital admission and were analyzed in relation to the coronary severity stenosis, assessed by the Gensini-score and the number of coronary narrowed vessels. Other clinical parameters, including insulin levels, HOMA-IR, hsCRP, glycaemic and lipid profile, and left-ventricular ejection fraction were also assessed.

Results

Serum RBP4 levels were significantly elevated in patients with CAD compared to non-CAD patients (39.29  ± 11.72 mg/L vs. 24.83  ± 11.27 mg/L, p < 0.001). We did not observe a significant difference in RBP4 levels between AMI and SA subgroups (p = 0.734). Logistic regression analysis revealed an independent association of CAD presence with serum RBP4 (β = 0.163, p = 0.006), and hsCRP (β = 0.122, p = 0.022) levels, in the whole study group. Among variables, hsCRP (β = 0.220), HDL (β = β0.150), and RBP4 (β = 0.297), correlated in both univariate and multivariate analysis with CAD severity (R² = 0.422, p < 0.001). Similarly, RBP4 concentrations increased with the number of coronary narrowed vessels (p < 0.05).

Conclusion

Patients with CAD, both SA and AMI, showed elevated RBP4 serum levels. Notably, increased RBP4 concentration seemed to independently correlate with CAD severity, but no with AMI.

Trial registration

The ClinicalTrials.gov Identifier is: NCT00636766

     

Elevated levels of serum chemerin in patients with obstructive sleep apnea syndrome

Context: Chemerin is implicated to be correlated with obesity and inflammation.

Objective: This study aims to investigate whether serum chemerin is associated with the presence of obstructive sleep apnea syndrome (OSAS).

Methods: A total of 132 patients with OSAS and 108 healthy subjects were enrolled in this study.

Results: Serum chemerin levels were significantly elevated in OSAS patients (120.93 ± 25.84 µg/L vs. 107.51 ± 20.41 µg/L). Multivariable logistic regression analysis revealed that serum chemerin levels were an independent determinant of the presence of OSAS (OR 1.030, 95% CI 1.016–1.045; p < 0.001). Serum chemerin levels in severe OSAS patients were significantly higher compared with those in mild and moderate OSAS patients (p = 0.015 and p = 0.020, respectively). Spearman correlation analysis indicated that serum chemerin levels were correlated with the severity of OSAS (r = 0.210, p = 0.016). Serum chemerin were positively correlated with waist circumference (r = 0.164, p = 0.008), body mass index (r = 0.158, p = 0.014), systolic blood pressure (r = 0.135, p = 0.037), homeostasis model assessment of insulin resistance (r = 0.140, p = 0.031), C-reactive protein (r = 0.202, p = 0.002), and apnea–hypopnea index (r = 0.152, p = 0.022).

Conclusion: Elevated serum chemerin levels could be an independent predicting marker of the presence and severity of OSAS.     

Serum Levels of Soluble CD26/Dipeptidyl Peptidase-IV in Type 2 Diabetes Mellitus and Its Association with Metabolic Syndrome and Therapy with Antidiabetic Agents in Malaysian Subjects

BackgroundA soluble form of CD26/dipeptidyl peptidase-IV (sCD26/DPP-IV) induces DPP-IV enzymatic activity that degrades incretin. We investigated fasting serum levels of sCD26/DPP-IV and active glucagon-like peptide-1 (GLP-1) in Malaysian patients with type 2 diabetes mellitus (T2DM) with and without metabolic syndrome (MetS), as well as the associations between sCD26/DPP-IV levels, MetS, and antidiabetic therapy.MethodsWe assessed sCD26/DPP-IV levels, active GLP-1 levels, body mass index (BMI), glucose, insulin, A1c, glucose homeostasis indices, and lipid profiles in 549 Malaysian subjects (including 257 T2DM patients with MetS, 57 T2DM patients without MetS, 71 non-diabetics with MetS, and 164 control subjects without diabetes or metabolic syndrome).ResultsFasting serum levels of sCD26/DPP-IV were significantly higher in T2DM patients with and without MetS than in normal subjects. Likewise, sCD26/DPP-IV levels were significantly higher in patients with T2DM and MetS than in non-diabetic patients with MetS. However, active GLP-1 levels were significantly lower in T2DM patients both with and without MetS than in normal subjects. In T2DM subjects, sCD26/DPP-IV levels were associated with significantly higher A1c levels, but were significantly lower in patients using monotherapy with metformin. In addition, no significant differences in sCD26/DPP-IV levels were found between diabetic subjects with and without MetS. Furthermore, sCD26/DPP-IV levels were negatively correlated with active GLP-1 levels in T2DM patients both with and without MetS. In normal subjects, sCD26/DPP-IV levels were associated with increased BMI, cholesterol, and LDL-cholesterol (LDL-c) levels.ConclusionSerum sCD26/DPP-IV levels increased in T2DM subjects with and without MetS. Active GLP-1 levels decreased in T2DM patients both with and without MetS. In addition, sCD26/DPP-IV levels were associated with Alc levels and negatively correlated with active GLP-1 levels. Moreover, metformin monotherapy was associated with reduced sCD26/DPP-IV levels. In normal subjects, sCD26/DPP-IV levels were associated with increased BMI, cholesterol, and LDL-c.     

Relationship between serum high sensitivity C-reactive protein with angiographic severity of coronary artery disease and traditional cardiovascular risk factors

Serum high-sensitivity C-reactive protein (hs-CRP) is predictive of coronary artery disease (CAD). The aim of this study was to examine the possible association of hs-CRP with presence and severity of CAD and traditional CAD risk factors. This case-control study was carried out on 2,346 individuals from September 2011 to May 2013. Of these 1,187 had evidence of coronary disease, and were subject to coronary angiography, and the remainder were healthy controls (n = 1,159). Characteristics were determined using standard laboratory techniques and serum Hs-CRP levels were estimated using enzyme-linked immunosorbent assay (ELISA) kits, and severity of CAD was assessed according to the score of obstruction in coronary artery. Serum hs-CRP levels were higher in those with severe coronary disease, who had stenosis ≥ 50% stenosis of at least one coronary artery (all p < 0.001 vs. individuals in healthy control), and correlated significantly with the score for coronary artery disease (all p < 0.01). After adjustment for conventional risk factors, regression analysis revealed that smoking habits, fasting blood glucose, total cholesterol, high-density lipoprotein, hs-CRP, blood pressure, anxiety, dietary intake of vitamin E, and cholesterol remained as independent determinants for angiographic severity of CAD. The area under the receiving operating characteristic (ROC) curve for serum hs-CRP was 0.869 (CI 95% 0.721–0.872, p < 0.001). The optimal values for the cut-off point was a serum hs-CRP of 2.78 mg/l (sensitivity 80.20%, specificity 85%) to predict severity of CAD. Increased serum hs-CRP levels are significantly associated with angiographic severity of CAD, suggesting its value as a biomarkers for predicting CAD.     

血清网膜素-1 与绝经后女性冠心病的相关性

目的：网膜素是最近发现的脂肪因子,肥胖或2 型糖尿病（diabetes mellitus, DM）患者血清网膜素-1 较正常者明显降低。本 次研究主要为观察绝经后女性血清网膜素-1 水平与冠心病的相关性。方法：选取我院心内科住院有心绞痛症状,并行冠脉造影的 105 例绝经后女性患者。依据冠脉造影结果分为冠心病组(67 例)和对照组例（3）,常规收集临床资料,包括年龄、体重指数（body mass index, BMI）、吸烟史、高血压病史、糖尿病史及血液生化和血脂指标;酶联免疫吸附剂测定(enzyme linked immunosorbent assay, ELISA)法检测血清网膜素-1 浓度。结果：冠心病组血清网膜素-1 水平显著低于对照组（205.62± 73.31 vs 401.64± 146.79, P<0.001）。单因素logistic回归分析示吸烟、高血压病史、糖尿病史、高脂血症史、网膜素-1 水平降低是冠心病组的独立危险因素 (P<0.05)。多因素logistic 回归分析示血清网膜素-1 水平降低是冠心病组的独立危险因素(P<0.001)。结论：绝经后女性血清网膜素 -1 水平下降是冠心病的独立危险因素,可能可成为绝经后女性冠心病的预测指标。     

Retinol binding protein 4 levels relate to the presence and severity of coronary artery disease

BackgroundThe previous studies have showed that serum retinol binding protein 4 (RBP4) levels increase in metabolic disorders which are closely associated with cardiovascular diseases (CVD). However, the human studies investigating the role of RBP4 in CVD are conflicted. Therefore, we aimed to evaluate the relationship between RBP4 with the presence and severity of coronary artery disease (CAD) in this study.Methods55 patients with presenting acute coronary syndrome (ACS) and 43 control subjects who had various cardiovascular risk factors with normal coronary artery on coronary angiography were included in this study. The serum RBP4 concentrations were measured using ELISA method, clinically and anatomically score models were used to assess the severity of coronary lesion.ResultsSerum RBP4 levels were significantly higher in patients with ACS compared to the without ACS (68.40 ± 47.94 mg/L vs. 49.46 ± 13.64 mg/L; p = 0.014). RBP4 was correlated with GENSINI and SYNTAX I score (r = 0.286 p = 0.034; r = 0.403 p = 0.002 respectively). However, there was no relationship between RBP4 and GRACE score.ConclusionsThe serum RBP4 levels increase in patients with CAD and its increased levels may be correlated with CAD severity.     

Thyroid Function and Metabolic Syndrome: A Cross-Sectional Study in Obese and Overweight Patients

Objective: Metabolic syndrome (MetS) is associated with increased risks of developing cardiovascular disease and type 2 diabetes. Thyroid dysfunction is also a known cardiovascular risk factor. In obese patients, serum thyroid-stimulating hormone (TSH) levels tend to be higher than in lean controls. The objective of this study was to assess potential associations between serum TSH levels and MetS as well as individual components of MetS.Methods: This was a cross-sectional observational study of obese and overweight patients seen for initial evaluation at the Boston Medical Center weight-management clinic between February 1, 2013 and February 1, 2014. Demographic, anthropometric, and laboratory data including serum TSH, insulin, glucose, hemoglobin A_1c, and lipid levels were obtained from electronic medical records. Associations between serum TSH levels and presence of MetS and its components were assessed.Results: A total of 3,447 patients, 75.6% female and 38% African American, without known thyroid dysfunction, were included. Mean ± SD age was 46.74 ± 15.11 years, and mean ± SD body mass index was 36.06 ± 9.89 kg/m². Among 1,005 patients without missing data, the prevalence of MetS was 71.84%. In patients with MetS, the median serum TSH was 1.41 μIU/mL, compared with 1.36 μIU/mL in patients without MetS (P = .45). In multivariate models, there was no significant association between serum TSH levels and the presence of MetS, adjusting for age, sex, race, education, socioeconomic status, and smoking. There were also no significant associations between serum TSH and individual components of the MetS.Conclusion: Serum TSH level does not appear to be a potentially modifiable risk factor for MetS in obese and overweight individuals.Abbreviations: BMI = body mass index FT₄ = free thyroxine HDL-C = high-density-lipoprotein cholesterol HbA_1c = hemoglobin A_1c MetS = metabolic syndrome SE = standard error TSH = thyroid-stimulating hormone     

Paraoxonase (PON)1 Q192R functional genotypes and PON1 Q192R genotype by smoking interactions are risk factors for the metabolic syndrome,but not overweight or obesity

Abstract

Background

The metabolic syndrome (MetS) is a complex of multiple risk factors that contribute to the onset of cardiovascular disorder, including lowered levels of high-density lipoprotein (HDL) and abdominal obesity. Smoking, mood disorders, and oxidative stress are associated with the MetS. Paraoxonase (PON)1 is an antioxidant bound to HDL, that is under genetic control by functional polymorphisms in the PON1 Q192R coding sequence.

Aims and methods

This study aimed to delineate the associations of the MetS with plasma PON1 activity, PON1 Q192R genotypes, smoking, and mood disorders (major depression and bipolar disorder), while adjusting for HDL cholesterol, body mass index, age, gender, and sociodemographic data. We measured plasma PON1 activity and serum HDL cholesterol and determined PON1 Q192R genotypes through functional analysis in 335 subjects, consisting of 97 with and 238 without MetS. The severity of nicotine dependence was measured using the Fagerström Nicotine Dependence Scale.

Results

PON1 Q192R functional genotypes and PON1 Q192R genotypes by smoking interactions were associated with the MetS. The QQ and QR genotypes were protective against MetS while smoking increased metabolic risk in QQ carriers only. There were no significant associations between PON1 Q192R genotypes and smoking by genotype interactions and obesity or overweight, while body mass index significantly increased MetS risk. Smoking and especially severe nicotine dependence are significantly associated with the MetS although these effects were no longer significant after considering the effects of the smoking by PON1 Q192R genotype interaction. The MetS was not associated with mood disorders, major depression or bipolar disorder.

Discussion

PON1 Q192R genotypes and genotypes by smoking interactions are risk factors for the MetS that together with lowered HDL and increased body mass and age contribute to the MetS.     

High‐Sensitivity C‐Reactive Protein in Japanese Patients with Type 2 Diabetes

Objective: To assess the relationship between high‐sensitivity (HS) C‐reactive protein (CRP) and metabolic syndrome (MetS) or atherosclerosis and to assess effects of strict metabolic control on the degree of inflammation and MetS in patients with type 2 diabetes. Research Methods and Procedures: Four hundred thirteen patients with diabetes were enrolled in the cross‐sectional study. Of these 413 patients, 161 patients were further admitted for 2.4 ± 0.4 weeks (mean ± SD) to investigate the change in HS‐CRP or other parameters under strict metabolic control. Results: Log‐transformed HS‐CRP value (log HS‐CRP) was strongly correlated with BMI (r = 0.448, p < 0.01). Log HS‐CRP was also correlated with the presence of MetS or each component of MetS. Furthermore, a positive significant trend in HS‐CRP levels was shown with an increasing number of MetS components (p < 0.05). Log HS‐CRP showed a significant positive correlation with carotid artery intima‐media thickness (IMT) (r = 0.152, p < 0.01). In multiple step‐wise regression analysis, BMI, hemoglobin A_1c, right IMT, duration of diabetes, and triglyceride were selected as explanatory variables for log HS‐CRP (R² = 0.412). Under strict metabolic control, HS‐CRP was significantly (p < 0.01) lower, together with lower levels of other markers for MetS. The change in HS‐CRP was significantly correlated with the change in BMI (r = 0.161, p = 0.04). Discussion: In subjects with type 2 diabetes, HS‐CRP levels are related to MetS and subclinical atherosclerosis. Strict weight management and metabolic control were associated with a reduction in HS‐CRP levels, and changes in HS‐CRP were related to changes in weight, supporting the hypothesis that lifestyle modification reduces inflammation and the risk of CHD.     

Is serum fibroblast growth factor 21 associated with the severity or presence of coronary artery disease?

BackgroundRecent studies have shown that increased circulating concentrations of fibroblast growth factor 21 (FGF21) are associated with obesity, metabolic disorder, and atherosclerosis. However the relationship between FGF21 and coronary artery disease (CAD) is controversial This study was planned to investigate the role of FGF21 in CAD development and CAD severity.MethodsSeventy-eight patients with stable angina pectoris (SAP) (lesion positive) and 40 control patients (lesion negative) with similar cardiovascular risk factors were included in the study. Serum FGF21 levels were measured by ELISA method. CAD severity was evaluated by using SYNTAX and GENSINI risk scores.ResultsFGF21 concentrations were found significantly higher in the SAP group than in the control group. [101.18 ± 141.62 vs. 47.93 ± 58.74 pg/mL; p = 0.03], no correlation was found between the SYNTAX (r = 0.146 and p = 0.134) and GENSINI (r = 0.211 and p = 0.084) scores with serum FGF21 levels. There was a negative relationship between serum FGF21 and serum HDL-C levels in correlation analysis (r = - 0.272; p = 0.026).ConclusionsThe serum FGF21 levels are different between SAP and control patients. FGF21 is a marker for CAD diagnosis, but not for the evaluation of CAD severity.     

Characterization of soluble thrombomodulin levels in patients with stage 3–5 chronic kidney disease

Abstract

Objective: This study aims to test the serum levels of soluble thrombomodulin (TM) in patients with chronic kidney disease (CKD)3–5 and to assess their connection with the different stages and severity of disease.

Methods: Sixty-seven patients with CKD are included, disease severity was evaluated accordingly to CKD staging and clinical data is collected. Nineteen healthy volunteers served as healthy controls. Serum soluble TM is analyzed by ELISA.

Results: The levels of soluble TM in all patients with CKD were significantly higher than those of healthy controls (p?<?0.001). CKD5 patients showed higher serum levels of soluble TM, in comparison to CKD4 patients (p?=?0.001), CKD3 patients (p?<?0.001), and healthy controls (p?<?0.001). The correlation analysis revealed significant correlation between serum soluble TM and disease severity (r?=?0.714, p?<?0.001). Serum soluble TM was found to be correlated with eGFR (r?=??0.766; p?<?0.001) and serum creatinine (r?=?0.778, p?<?0.001).

Conclusion: Soluble TM concentrations significantly increase in the CKD patients and are associated with the severity of the disease. Soluble TM may play critical roles in the development of CKD, as a biomarker of endothelial cells damage, anticoagulation and anti-inflammation.     

FABP4 and omentin-1 gene expression in epicardial adipose tissue from coronary artery disease patients

Omentin-1 and fatty acid-binding protein 4 (FABP4) are adipose tissue adipokines linked to obesity-associated cardiovascular complications. The aim of this study was to investigate epicardial adipose tissue (EAT) omentin-1 and FABP4 gene expression in obese and non-obese patients with coronary artery disease (CAD). Omentin-1 and FABP4 mRNA levels in EAT and paired subcutaneous adipose tissue (SAT) as well as adipokine serum concentrations were assessed in 77 individuals (61 with CAD; 16 without CAD (NCAD)). EAT FABP4 mRNA level was decreased in obese CAD patients when compared to obese NCAD individuals (p=0.001). SAT FABP4 mRNA level was decreased in CAD patients compared to NCAD individuals without respect to their obesity status (p=0.001). Omentin-1 mRNA level in EAT and SAT did not differ between the CAD and NCAD groups. These findings suggest that omentin-1 gene expression in adipose tissue is not changed during CAD; downregulated FABP4 gene expression in SAT is associated with CAD while EAT FABP4 gene expression is decreased only in obesity-related CAD.     

Soluble glycoprotein 130 is inversely related to severity of coronary atherosclerosis

Purpose: Recent studies indicate that the effects of interleukin 6 (IL-6) realized via soluble IL-6 receptor (sIL-6R) facilitate the development of various pathological processes. Soluble gp130 (sgp130) is a naturally occurring inhibitor of signal transduction via this pathway. In this study, we assessed the relationship between circulating levels of IL-6, sIL-6R and sgp130 and severity of coronary atherosclerosis in patients with stable coronary artery disease (CAD).

Methods: Plasma levels of IL-6, sIL-6R and sgp130 were measured in patients with atherosclerotic coronary lesions (n?=?128, group 1) and with intact coronary arteries (n?=?48, group 2). The severity of coronary atherosclerosis was evaluated by the number of affected arteries and by Gensini Score index.

Results: Circulating IL-6 levels in group 1 were significantly higher than those in group 2. The levels of sIL-6R did not differ considerably in both the groups. The levels of sgp130 in group 1 were significantly lower than in group 2. A negative correlation has been revealed between sgp130 levels and the number of affected coronary arteries and Gensini Score index.

Conclusions: Serum concentration of sgp130 in patients with stable CAD is inversely related to severity of coronary damage. Low sgp130 level may serve as an additional indicator of coronary atherosclerosis severity.     

Serum levels of adipocyte fatty acid-binding protein are associated with the severity of coronary artery disease in Chinese women

Background

Adipocyte fatty acid-binding protein (A-FABP) has been described as a novel adipokine, playing an important role in the development of metabolic syndrome, type 2 diabetes and atherosclerosis. In this study, we investigated the relationship between serum levels of A-FABP and the presence and severity of coronary artery disease (CAD) in Chinese subjects.

Methodology/Principal Findings

Circulating A-FABP level was determined by ELISA in 341 Chinese subjects (221 men, 120 women) who underwent coronary angiography. A-FABP levels in patients with CAD were significantly higher compared with non-CAD subjects (P = 0.029 in men; P = 0.031 in women). Serum A-FABP increased significantly in multi-vessel diseased patients than in non-CAD subjects (P = 0.011 in men, P = 0.004 in women), and showed an independent correlation with coronary atherosclerosis index (standardized β = 0.173, P = 0.025). In multiple logistic regression analysis, serum A-FABP was an independent risk factor for CAD in women (OR = 5.637, 95%CI: 1.299-24.457, P = 0.021). In addition, amino terminal pro-brain natriuretic peptide (NT-proBNP) was demonstrated to be positively and independently correlated with A-FABP (standardized β = 0.135, P = 0.027).

Conclusions/Significance

Serum A-FABP is closely associated with the presence and severity of CAD in Chinese women.     

Serum prolidase activity and oxidative–antioxidative status in patients with developmental dysplasia of the hip and its relationship with radiographic severity

Background: We aimed to investigate serum prolidase activity and to investigate its association with oxidative–antioxidative status in patients with developmental dysplasia of the hip (DDH).

Methods: Oxidative status parameters, including lipid hydroperoxide (LOOH), total oxidant status (TOS), and the oxidative stress index (OSI), and antioxidative status parameters, free sulfhydryl groups (Total –SH), and total antioxidative capacity (TAC), as well as serum prolidase activity were assessed in patients with DDH (n?=?93), and in healthy controls (n?=?82). The severity of dysplasia was evaluated according to the Tonnis grading system.

Results: Serum prolidase activity and the oxidant parameters (LOOH, TOS, and OSI) were significantly higher and the antioxidant parameters (Total –SH and TAC) were significantly lower in patients with DDH compared to the controls (P?P?P?Conclusion: Increased levels of serum prolidase activity, LOOH, TOS, and OSI, and decreased levels of total –SH and TAC, may be associated with DDH, and these parameters may be useful adjunctive tools to assess the severity of DDH.     

Bile acid metabolites in serum: intraindividual variation and associations with coronary heart disease, metabolic syndrome and diabetes mellitus

Bile acids (BAs) regulate glucose and lipid metabolism. In longitudinal and case-control-studies, we investigated the diurnal variation of serum concentrations of the 15 major BAs as well as the biosynthetic precursor 7α-hydroxy-4-cholesten-3-one (C4) and their associations, respectively, with coronary artery disease (CAD), diabetes mellitus type 2 (T2DM), and non-diabetic metabolic syndrome (MetS). In hourly taken blood samples of four healthy probands, the intraindividual 24 h variation of C4, conjugated and unconjugated BAs ranged from 42% to 72%, from 23% to 91%, and from 49% to 90%, respectively. Conjugated BA concentrations mainly increased following food intake. Serum levels of C4 and unconjugated BAs changed with daytime with maxima varying interindividually between 20h00 and 1h00 and between 3h00 and 8h00, respectively. Comparisons of data from 75 CAD patients with 75 CAD-free controls revealed no statistically significant association of CAD with BAs or C4. Comparisons of data from 50 controls free of T2DM or MetS, 50 MetS patients, and 50 T2DM patients revealed significantly increased fasting serum levels of C4 in patients with MetS and T2DM. Multiple regression analysis revealed body mass index (BMI) and plasma levels of triglycerides (TG) as independent determinants of C4 levels. Upon multivariate and principle component analyses the association of C4 with T2DM and/or MetS was not independent of or superior to the canonical MetS components. In conclusion, despite large intra- and interindividual variation, serum levels of C4 are significantly increased in patients with MetS and T2DM but confounded with BMI and TG.     

The MMP-9 -1562 C/T Polymorphism in the Presence of Metabolic Syndrome Increases the Risk of Clinical Events in Patients with Coronary Artery Disease

Background and Objectives

Elevated levels of matrix metalloproteinase (MMP)-9 have been associated with the metabolic syndrome (MetS) and cardiovascular events. The MMP-9 −1562 C/T polymorphism has furthermore been shown as a risk factor for coronary artery disease (CAD). The non-favourable cardiometabolic state in MetS may increase the risk. We aimed to investigate the influence of MMP-9 −1562 C/T polymorphism in subjects with CAD and MetS.

Methods

Patients (n = 1000) with verified CAD stratified in Mets +/− (n = 244/756), were analyzed for the MMP-9 −1562 C/T polymorphism and related to clinical events after 2 years follow-up. Serum levels of total MMP-9 and tissue inhibitor of matrix metalloproteinases (TIMP)-1were analyzed in all, whereas MMP-9 activity, extracellular matrix metalloproteinase inducer (EMMPRIN), and expression of the two genes were analyzed in a subset of 240 randomly selected patients.

Results

Totally, 106 clinical endpoints were recorded. In MetS; the T-allele associated with 5.5 fold increase in event rate (p<0.0001), increased with number of MetS components, a 117% increase in total MMP-9 levels (TT homozygous, p = 0.05), significantly higher total- and endogenous active MMP-9 and TIMP-1 levels (p<0.01 all), and EMMPRIN was inversely correlated with pro- and endogenous active MMP-9 (p<0.05, both). In non-MetS; the T-allele was not associated with new events, nor higher MMP-9 levels. EMMPRIN was significantly correlated with total MMP-9 and TIMP-1 (p<0.01, both) and the two genes were inter-correlated (p<0.001).

Conclusion

In CAD patients with MetS, the MMP-9 T-allele increased the risk of clinical events, probably mediated through elevated MMP-9 levels and altered MMP-9 regulation.