Circulating resistin protein and mRNA concentrations and clinical severity of coronary artery disease

Introduction: Previous studies have implicated a strong link between circulating plasma resistin and coronary artery disease (CAD). The aim of this study was to evaluate the differences in peripheral blood mononuclear cells (PBMC) resistin mRNA and its plasma protein concentrations between the patients with CAD of different clinical severity. Material and methods: This study included 33 healthy subjects as the control group (CG) and 77 patients requiring coronary angiography. Of the latter 30 was CAD negative whereas 47 were CAD positive [18 with stable angina pectoris (SAP) and 29 with acute coronary syndrome (ACS)]. Circulating resistin was measured by ELISA; PBMC resistin mRNA was determined by real-time PCR. Results: Resistin protein was significantly higher in the ACS group compared to the CG (P = 0.001) and the CAD negative group (P = 0.018). Resistin mRNA expression did not vary across the study groups, despite the positive correlation seen with plasma resistin (rho = 0.305, P = 0.008). In patients, plasma resistin and PBMC resistin mRNA negatively correlated with HDL-C (rho = -0.404, P lt 0.001 and rho = -0.257, P = 0.032, respectively). Furthermore, the highest plasma resistin tertile showed the lowest HDL-C (P = 0.006). Plasma resistin was positively associated with serum creatinine (rho = 0.353, P = 0.002). Conclusion: Significant increase of plasma resistin in patients with ACS compared to CG and CAD negative patients was observed. Despite no change in PBMC resistin mRNA in different disease conditions a positive association between resistin mRNA and resistin plasma protein was evident. Both plasma resistin and PBMC resistin mRNA were negatively associated with plasma HDL-C, and plasma resistin positively with serum creatinine

Lack of association between low HDL-cholesterol and elevated circulating cellular adhesion molecules in normolipidemic CAD patients and healthy subjects

High plasma HDL-cholesterol (HDL-c) is a well-established protective factor in coronary artery disease (CAD). One of its potential protective mechanisms is the inhibition of the cytokine-induced upregulation of expression of cellular adhesion molecules (CAMs). High sCAM levels were found to be associated with low HDL-c in some studies performed mostly in hyperlipidemic subjects, but this association has not yet been investigated in CAD patients. In addition, conflicting results were obtained from in vitro studies that explored the proposed HDL effect on cytokine-induced CAM expression. The aim of the present case-control study was to investigate whether low HDL-c values are associated with CAM overexpression in normolipidemic CAD patients and healthy individuals, matched according to age and gender. Plasma HDL-c, sICAM-1, sVCAM-1, and sE-selectin were measured in 37 normolipidemic patients with angiographically verified coronary artery disease and in 52 healthy normolipidemic subjects. The sCAM values obtained in the subjects (patients or controls) with low HDL-c levels ( lt 1.03 mmol/L) were compared with the values in the subjects with high HDL-c (>= 1.03 mmol/L). No significant difference was found between sICAM-1, sVCAM-1, and E-selectin values obtained in subjects with low and high HDL-c, either among the patients or the healthy controls. In conclusion, low HDL-c levels are not associated with CAM overexpression in normolipidemic CAD patients and healthy subjects

Uticaj hipertrigliceridemije na male, guste LDL i HDL čestice u koronarnoj arterijskoj bolesti

Alterations in serum lipoprotein levels contribute to the progression of atherosclerosis in coronary artery disease (CAD). Screening for the presence of small, dense low-density (LDL) and high-density lipoprotein (HDL) particles and identification of the factors affecting their excessive production, could have beneficial effects on reducing the risk of future cardiovascular events. In this study, we investigated the effect of serum triglyceride concentration on LDL and HDL size and subclasses in 181 CAD patients and 178 healthy controls. LDL and HDL particles were separated by polyacrylamide gradient gel electrophoresis, while serum lipid parameters were determined by routine laboratory methods. CAD patients had significantly smaller LDL and HDL particle sizes (P lt 0.001), more LDL III, but less HDL 2b subclasses (P lt 0.05) than controls. In CAD group, higher TG levels were associated with smaller LDL and HDL sizes and lower proportions of LDL I subclasses. Patients with hypertriglyceridemia had reduced LDL diameters (P lt 0.01) and higher proportions of small, dense LDL particles (P lt 0.05) than normotrigliceridemic patients. In addition, hypertriglyceridemic patients had HDL subclasses distribution shifted towards smaller particles. Our results indicate that serum TG level is the main lipid risk factor that determines the amount of small, dense LDL and HDL particles in CAD.Poremećaji koncentracije lipoproteina doprinose progresiji ateroskleroze u koronarnoj arterijskoj bolesti (KAB). Ispitivanjem zastupljenosti malih, gustih čestica lipoproteina niske (LDL) i visoke gustine (HDL), kao i otkrivanjem faktora koji utiču na njihovo povećano stvaranje, moguće je smanjiti rizik za pojavu budućih kardiovaskularnih događaja. U ovoj studiji ispitivali smo uticaj koncentracije triglicerida (TG) na veličinu i raspodelu LDL i HDL subfrakcija kod 181 pacijenta sa KAB i 178 zdravih osoba. LDL i HDL subfrakcije su razdvojene metodom vertikalne elektroforeze na gradijentu poliakrilamida, a koncentracije lipidnih parametara su određene rutinskim laboratorijskim metodama. Utvrdili smo da KAB pacijenti imaju značajno manje dijametre LDL i HDL čestica (P lt 0,001), veći udeo LDL III, a manje HDL 2b subfrakcija (P lt 0,05). U KAB grupi povišena koncentracija TG bila je u korelaciji sa manjim LDL i HDL dijametrima i nižim udelom LDL I subfrakcija. Pacijenti sa hipertrigliceridemijom imali su manje LDL dijametre (P lt 0,01) i veći udeo malih, gustih LDL čestica (P lt 0,05) u odnosu na normotrigliceridemične pacijente. Sem toga, kod pacijenata sa hipertrigliceridemijom uočena je preraspodela HDL subfrakcija ka manjim česticama. Naši rezultati ukazuju da je koncentracija TG u serumu glavni lipidni faktor rizika koji determiniše količinu malih, gustih LDL i HDL čestica u KAB

Association of Serum Pentraxin-3 and High-Sensitivity C-Reactive Protein with the Extent of Coronary Stenosis in Patients Undergoing Coronary Angiography

Background: We compared factors of inflammation high sensitivity C-reactive protein (hsCRP) and pentraxin-3 (PTX3), and we explored their relationship with coronary artery disease (CAD). Also, we tested the usefulness of hsCRP and PTX3 in the risk assessment of coronary stenosis development and the diagnostic ability of these biomarkers to detect disease severity. Methods: The study group consisted of 93 CAD patients undergoing coronary angiography. Patients were divided into CAD(0), representing subclinical stenosis, and CAD (1-3), representing significant stenosis in one, two or three vessels. Results: We determined the concentration of lipid status parameters, hsCRP and PTX3. We found significantly lower PTX3 and hsCRP concentrations in CAD(0) than in CAD(1-3) group. Concentration of PTX3 showed an increasing trend with the increasing number of vessels affected. The area under ROC curve (AUC) for the combinations of hsCRP and PTX3 with lipid parameters had useful accuracy for detecting CAD(1-3) patients (AUC=0.770, p lt 0.001). Conclusion: PTX3 is a promising independent diagnostic marker for identifying patients with CAD, and a useful indicator of disease progression. In all the analyses PTX3 showed better performance than hsCRP. A combination of PTX3, hsCRP with the lipid status parameters provides risk stratification of the development of coronary stenosis and better classification than their individual application

Smaller HDL particles are associated with absence of obstructive coronary artery disease in stable angina pectoris patients

Background A research on novel cardiovascular risk factors is mainly focused on patients with clinically verified coronary artery disease (CAD), while less is known about their presence in symptomatic patients, but without angiographically proven occlusion of coronary arteries. The aim of this study was to compare plasma low-density lipoprotein (LDL) and high-density lipoprotein (HDL) size and subclasses in stable angina patients with and without significant obstructive CAD. Methods LDL and HDL subclasses were analysed in 100 stable angina patients with >= 50% of obstruction and 40 patients with less than 50% of luminal narrowing, as assessed by coronary angiography. Results Patients with lt 50% of obstruction had reduced mean HDL size and higher proportion of small HDL particles (P lt 0.05). HDL size and proportion of small HDL particles were significant and independent predictors of obstructive CAD (P lt 0.05, respectively). Conclusions Stable angina patients wit

Superoxide dismutase isoenzymes gene expression in peripheral blood mononuclear cells in patients with coronary artery disease

Background: Coronary artery disease (CAD) is one of the most important causes of mortality and morbidity in wide world population. Dyslipidemia, inflammation and oxidative stress may contribute to disruption of endothelium structure and function, atherosclerosis and CAD. Our study was aimed to determine whether Cu/Zn superoxide dismutase (Cu/Zn SOD) and Mn superoxide dismutase (Mn SOD) gene expression could be modulated by oxidative stress in CAD patients. Methods: This study included 77 CAD patients and 31 apparently healthy persons. Serum lipid levels, high sensitivity C-reactive protein (hsCRP), total antioxidant status (TAS) and thiobarbituric acid-reacting substances (TBARS) were measured. SOD isoenzymes gene expression was determined in peripheral blood mononuclear cells using quantitative polymerase chain reaction. Results: Mn SOD messenger ribonucleic acid (mRNA) levels were significantly lower in CAD patients than in controls (p=0.011), while Cu/Zn SOD mRNA levels did not change significantly between tested groups (p=0.091). We found significantly lower high-density lipoprotein-cholesterol (HDL-c) (p lt 0.001) and TAS (p lt 0.001) levels and significantly higher hsCRP (p=0.002) and TBARS (p lt 0.001) in CAD patients than in controls. There were significant positive correlations between TAS and Mn SOD mRNA (rho=0.243, p=0.020) and TAS and Cu/Zn SOD mRNA (rho=0.359, p lt 0.001). TBARS negatively correlated only with Cu/Zn SOD mRNA (rho=-0.215, p=0.040). TAS levels remained independent predictor for Mn SOD mRNA levels (OR = 2.995, p=0.034). Conclusions: Results of this study showed that Mn SOD gene expression were decreased in CAD patients compared to controls and can be modulated by nonenzymatic antioxidant status in blood

The significance of pre-existing knowledge of the latest guidelines for cardiopulmonary resuscitation in successful basic life support education of Belgrade sixth year medical students

Introduction. The latest Guidelines for cardiopulmonary resuscitation (CPR) were published in 2010. The aim of the implementation of basic life support (BLS) guidelines is the introduction of uniform criteria within the domain of cardiac arrest diagnostics and treatment both for lay rescuers and first line lifesavers without formal medical education as well as for medical personnel who happen to be in the role of the event witness but without medical equipment and outside of their working place. Objective. The goal of this study was to investigate the significance of pre-existing knowledge of the latest 2010 Guidelines for CPR for achieving successful training in BLS among 6th year students of the Belgrade School of Medicine. Methods. In a five-month prospective study of 6th year medical students doing a clinical internship at the Belgrade Emergency Medical Services (EMS) were in a peer training on the application of BLS. At the beginning and at the end of the training program, the students had to pass entrance (E) and final (F) tests composed of 25 identical questions. Using the E test, the students’ knowledge of the latest CPR Guidelines was tested; they were classified into groups with pre-existing knowledge (group I) and groups without pre-existing knowledge (group II). By comparing data from E and F tests we analyzed the influence of training on the improvement of pre-existing knowledge or gaining new knowledge in BLS and first aid. Results. A total of 423 students were tested. The analysis of obtained data showed that in group I there was a statistically significant difference between correct and incorrect responses to eleven questions on the F and E tests. In group II there was a statistically significant difference between test responses in the E and F tests to 17 questions. In group II, knowledge additionally improved after training so that in the F test, a statistical significance in correct answers was achieved with regard to 8 questions in relation to the E test (p<0.05). There was a statistically significant difference between correct and inaccurate answers in tests F and E with regard to 10 questions. In the entire group of students, a total statistical significance (p<0.05) was achieved in answers to as much as 25 questions. Conclusion. Among 6th year medical students without pre-existing knowledge of the latest 2010 CPR Guidelines, BLS training considerably improved their previously acquired knowledge. Also, students with good pre-existing knowledge, showed a considerably higher level of acquired knowledge after implemented training. A future study with a longer follow-up period to estimate the effect on long-term retention of learning outcomes is needed

Da li pentraksin -3 doprinosi sniženju koncentracije lipoproteina niske gustine i terapiji statinima?

Statins have been shown to decrease inflammatory markers, especially high sensitivity C reactive protein (hsCRP), in a dose-dependent manner. Pentraxin-3 (PTX3) is another important inflammatory biomarker from the pentraxin family that provides useful prognostic information and facilitates diagnostics of cardiovascular diseases. This study investigated the effect of statin therapy on PTX3 and hsCRP concentrations and whether statins acted synergistically with PTX3 and hsCRP concentrations in lowering LDL-C. The study group consisted of 90 patients undergoing coronary angiography. The results showed that statins reduced PTX3 concentrations (p=0.031). PTX3 and hsCRP levels were significantly different between subclinical and severe stenosis groups (p=0.011 and p=0.009, respectively). Statin therapy was significantly associated with lower PTX3 and LDL-C levels in multiple logistic analyses. The probability that statin therapy would achieve target LDL-C values was highest in patients with low PTX3 values (OR=3.683, p=0.040), while multiplicative interaction was 23.3. The effect of statins on PTX3 reduction was higher than on hsCRP. It can be suggested that statin therapy was more successful in patients with low PTX3 values.Pokazano je da statini snižavaju koncentracije inflamatornih markera, posebno visoko osetljivog C reaktivnog proteina (hsCRP), pri čemu je sniženje zavisno od doze leka. Pentraksin- 3 (PTX3) je još jedan važan inflamatorni biomarker iz porodice pentraksina koji ima prognostičke karakteristike i olakšava dijagnozu kardiovaskularnih bolesti. U ovoj studiji je ispitivan efekat terapije statinima na koncentracije PTX3 i hsCRP, kao i sinergistički efekat terapije, koncentracija PTX3 i hsCRP u snižavanju LDL-C. U studiju je uključeno 90 pacijenata kojima je koronarnom angiografijom procenjeno suženje koronarnih krvnih sudova. Rezultati su pokazali da statini smanjuju koncentraciju PTX3 (p=0,031). Koncentracije PTX3 i hsCRP značajno se razlikuju između grupa sa subkliničkim (p=0,011) i teškim oblikom stenoze (p=0,009). Primenom multiple logističke regresione analize uočena je veza između terapije statinima i niskih koncentracija PTX3 i LDL-C. Verovatnoća da će terapija statinima postići ciljne vrednosti LDL- C bila je najveća kod pacijenata sa niskim vrednostima PTX3 (OR=3,683, p=0,040), dok je multiplikativna interakcija bila 23,3. Efekat statina na sniženje PTX3 bio je veći u odnosu na efekat koji ostvaruje na hsCRP. Može se sugerisati da je terapija statinima bila uspešnija kod pacijenata sa niskim vrednostima PTX3

Lipid and inflammatory markers for the prediction of coronary artery disease: A multi-marker approach

Background: Many studies have investigated the clinical accuracy of single lipid and inflammatory markers. in contrast, few have evaluated their potential for the detection of CAD using a multi-marker approach. Methods: The concentrations of lipid, lipoproteins, apolipoproteins, high sensitivity C-reactive protein (hs-CRP) and fibrinogen were measured by standard laboratory methods. Apolipoprotein (a) [apo(a)] phenotyping was performed by sodium dodecylsulphate-gel electrophoresis and immunoblotting. The lipid tetrad index (LTI) and the lipid pentad index (LPI) were calculated. Clinical accuracy of the examined parameters, indexes and a logistic regression model was assessed using receiving operative characteristic (ROC) curve analysis. Results: Logistic regression analysis indicated that non-HDL-c, hs-CRP, HDL-c and Lp(a) were significant independent predictors for CAD. The AUC for this model (0.802) was higher than AUCs for any single marker or index tested. Conclusions: We conclude that the performance of a logistic regression model for CAD prediction warrants its use in clinical practice