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<0.001) and TAS (p<0.001) levels and significantly higher hsCRP (p=0.002) and TBARS (p<0.001) in CAD patients than in controls. There were significant positive correlations between TAS and Mn SOD mRNA (ρ=0.243, p=0.020) and TAS and Cu/Zn SOD mRNA (r=0.359, p<0.001). TBARS negatively correlated only with Cu/Zn SOD mRNA (ρ=-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 non-enzymatic antioxidant status in blood.

Assessment of hypertension chronic care model: Pacic application in Bosnia and Herzegovina.

The objectives of this study were to evaluate patients' attitudes towards hypertension treatment according to the chronic care model and to assess the implementation of hypertension clinical guidelines in family medicine. The cross-sectional study was carried out in two randomly selected primary health care centers (Bijeljina and Prijedor), respectively in Bosnia and Herzegovina, covering the period between March and April 2016. This study sample consists of 791 respondents with hypertension purposing to measure specific actions and quality of care for hypertensive patients. The Patient Assessment of Chronic Illness Care (PACIC) was used. Treatment for the indicators of hypertension was assessed by analyzing patients' medical charts according to the recommendations of clinical guidelines. More than half of the evaluated indicators of treatment for hypertension were documented in medical charts of 84.07% patients. The average overall PACIC score was 4.18 (SD 0.59), being an average of the separate scores of 4.19 (SD 0.57) in men and 4.17 (SD 0.60) in women. Subscale means of PACIC were as follows: patient activation 4.33, delivery system design 4.36; goal setting 4.03; problem solving 4.51; follow-up and co-ordination 3.67. No statistically significant correlations in the overall score and subscale scores were found by demographic characteristics. Non-smokers had a significantly higher overall score compared to smokers (p = 0.001). As implementation of the guidelines became stronger, the reported PACIC scores rose. Continuing the education of patients in order to achieve better health care outcomes is imperative.

The relationship between causative microorganisms and cardiac lesions caused by infective endocarditis: New perspectives from the contemporary cohort of patients.

BACKGROUND: The etiology of infective endocarditis (IE) is changing. More aggressive forms with multiple IE cardiac lesions have become more frequent. This study sought to explore the relationship between contemporary causative microorganisms and IE cardiac lesions and to analyze the impact of multiple lesions on treatment choice. METHODS: In 246 patients hospitalized for IE between 2008 and 2015, cardiac lesions caused by IE were analyzed by echocardiography, classified according to the 2015 European Society of Cardiology guidelines and correlated with microbiological data. We defined a new parameter, the Echo IE Sum, to summarize all IE cardiac lesions in a single patient, enabling comprehensive comparisons between different etiologies and treatment strategies. RESULTS: Staphylococcus aureus was associated with the development of large vegetation (OR 2.442; 95% CI 1.220-4.889; p=0.012), non-HACEK bacteria with large vegetation (OR 13.662; 95% CI 2.801-66.639; p=0.001), perivalvular abscess or perivalvular pseudoaneurysm (OR 5.283; 95% CI 1.069-26.096; p=0.041), and coagulase-negative staphylococci (CoNS) with leaflet abscess or aneurysm (OR 3.451; 95% CI 1.285-9.266, p=0.014), and perivalvular abscess or perivalvular pseudoaneurysm (OR 4.290; 95% CI 1.583-11.627; p=0.004). The Echo IE Sum significantly differed between different etiologies (p<0.001), with the highest value in non-HACEK and the lowest in streptococcal endocarditis. Patients operated for IE had a significantly higher Echo IE Sum vs those who were medically treated (p<0.001). CONCLUSION: None of the IE cardiac lesions is microorganism-specific. However, more severe lesions were caused by S. aureus, CoNS, and non-HACEK bacteria. The highest propensity to develop multiple lesions was shown by the non-HACEK group. Higher Echo IE Sum in patients sent to surgery emphasized the importance of multiple IE cardiac lesions on treatment choice and potential usage of Echo IE Sum in patient management.

Association of adenylate cyclase-associated protein 1 with coronary artery disease.

BACKGROUND: Adenylate cyclase-associated protein 1 (CAP1) is a recently identified receptor for human resistin. As resistin has been related to CAD development and progression and CAP1 has never been evaluated in CAD, the aim of this study was to determine its peripheral blood mononuclear cells (PBMCs) mRNA in patients with CAD, and resistin plasma concentration, PBMCs resistin and CD36 mRNA, considering resistiǹs ability to stimulate CD36 expression in vitro. MATERIALS AND METHODS: This case-controlled study included 27 healthy subjects (CG) and 66 patients requiring coronary angiography. Of the latter, 42 had nonsignificant CAD whereas 24 had significant CAD. Circulating resistin was measured by ELISA; PBMCs CAP1, resistin and CD36 mRNA were determined by real-time PCR. RESULTS: Patients with significant as well as patients with nonsignificant CAD had significantly higher resistin concentrations compared to the CG (P < 0·001; P = 0·003). Resistin mRNA did not show significant difference between the investigated groups. CAP1 and CD36 mRNA were significantly higher in significant CAD (P < 0·001; P < 0·001, respectively) and nonsignificant CAD (P < 0·001; P < 0·001, respectively) compared to the CG; significant CAD showed significantly higher CD36 mRNA (P = 0·040) compared to the nonsignificant CAD group. Multiple linear regression analysis identified Tg and CD36 mRNA as independent predictors of CAP1 (R2  = 0·402; adjR2  = 0·376). CONCLUSION: Significant up-regulation of PBMCs CAP1, CD36 mRNA and plasma resistin found in significant CAD, as well as in nonsignificant CAD compared to CG, indicates that resistin could be able to exert its effects stronger on cells with up-regulated CAP1 mRNA thus contributing atherosclerosis development.

Can non-cholesterol sterols and lipoprotein subclasses distribution predict different patterns of cholesterol metabolism and statin therapy response?

BACKGROUND: Cholesterol homeostasis disorders may cause dyslipidemia, atherosclerosis progression and coronary artery disease (CAD) development. Evaluation of non-cholesterol sterols (NCSs) as synthesis and absorption markers, and lipoprotein particles quality may indicate the dyslipidemia early development. This study investigates associations of different cholesterol homeostasis patterns with low-density (LDL) and high-density lipoproteins (HDL) subclasses distribution in statin-treated and statin-untreated CAD patients, and potential use of aforementioned markers for CAD treatment optimization. METHODS: The study included 78 CAD patients (47 statin-untreated and 31 statin-treated) and 31 controls (CG). NCSs concentrations were quantified using gas chromatography- flame ionization detection (GC-FID). Lipoprotein subclasses were separated by gradient gel electrophoresis. RESULTS: In patients, cholesterol-synthesis markers were significantly higher comparing to CG. Cholesterol-synthesis markers were inversely associated with LDL size in all groups. For cholesterol homeostasis estimation, each group was divided to good and/or poor synthetizers and/or absorbers according to desmosterol and ß-sitosterol median values. In CG, participants with reduced cholesterol absorption, the relative proportion of small, dense LDL was higher in those with increased cholesterol synthesis compared to those with reduced synthesis (p<0.01). LDL I fraction was significantly higher in poor synthetizers/poor absorbers subgroup compared to poor synthetizers/good absorbers (p<0.01), and good synthetizers/poor absorbers (p<0.01). Statin-treated patients with increased cholesterol absorption had increased proportion of LDL IVB (p<0.05). CONCLUSIONS: The results suggest the existence of different lipoprotein abnormalities according to various patterns of cholesterol homeostasis. Desmosterol/ß-sitosterol ratio could be used for estimating individual propensity toward dyslipidemia development and direct the future treatment.

Higher circulating resistin protein and PBMCs resistin mRNA levels are associated with increased prevalence of small dense LDL particles in coronary artery disease patients.

Recent in vitro experiments have indicated that human resistin increases the number of lipoprotein particles secreted by the human hepatocytes and also influences their quality, in terms of generating more proatherogenic lipid particles. The aim of this study is to investigate associations of plasma resistin and peripheral blood mononuclear cells (PBMCs) resistin messenger RNA (mRNA) levels with different prevalence of small, dense low-density lipoprotein particles (sdLDL) in patients with indications for coronary angiography. This study included 65 patients requiring coronary angiography. There were 41 patients without significant stenosis and 24 patients with significant stenosis in at least one major coronary artery. Circulating resistin was measured by enzyme-linked immunosorbent assay; PBMC resistin mRNA was determined by real-time polymerase chain reaction. The LDL and high density lipoprotein subclasses were determined by gradient gel electrophoresis. Plasma resistin (P = 0.031) and PBMCs resistin mRNA (P = 0.004) were significantly higher in patients with proportion of sdLDL particles ≥ 50%, compared to the group with relative proportion of sdLDL particles < 50%. Plasma resistin correlated positively with creatinine (r = 0.456, P < 0.001) and resistin mRNA (r = 0.298, P = 0.014) but negatively with body mass index (r = -0.254, P = 0.034) and total cholesterol (r = -0.286, P = 0.021). Multiple linear regression analysis revealed LDL particle diameter as the only independent predictor of resistin mRNA (R(2) = 0.258; adjR(2) = 0.190). A significant association between resistin, both PBMCs mRNA and plasma protein, and the relative proportion of sdLDL particles in the circulation of coronary artery disease patients has been established, which implies that increased gene expression of resistin in PBMCs and higher resistin concentration in plasma are related to pro-atherogenic LDL particle phenotype.

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 (ρ=0.305, P=0.008). In patients, plasma resistin and PBMC resistin mRNA negatively correlated with HDL-C (ρ=-0.404, P<0.001 and ρ=-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 (ρ=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.

Are decreased AdipoR1 mRNA levels associated with adiponectin resistance in coronary artery disease patients?

The aim of the present study was to investigate if circulating adiponectin levels and the expression of AdipoR1 and AdipoR2 in peripheral blood mononuclear cells (PBMC) are altered in coronary artery disease (CAD) patients, with and without significant stenosis, compared to healthy patients. The present study included 69 patients with presenting symptoms of CAD (26 patients with significant stenosis and 43 patients without significant stenosis). The control group (CG) consisted of 33 healthy patients. Circulating adiponectin levels were measured by enzyme-linked immunosorbent assay, whereas AdipoR1 and AdipoR2 mRNA levels in PBMC were determined by real-time polymerase chain reaction. Adiponectin levels were significantly higher in patients with and without significant stenosis compared to the CG (P < 0.001 vs P = 0.006, respectively). Both patient groups had lower AdipoR1 levels compared to the CG (P < 0.001 vs P < 0.001, respectively). There were no significant differences in these parameters between the two patient groups. Adiponectin negatively correlated with body mass index, triglycerides, insulin and homeostasis model assessment of insulin resistance index (HOMA IR), and positively with high-denisty lipoprotein cholesterol in the CG. Glucose, insulin, and the HOMA IR index negatively correlated with adiponectin in patients. A positive correlation between adiponectin receptors was found in patients and the CG. Decreased AdipoR1 mRNA levels and increased circulating adiponectin in advanced stages of CAD, as well as in patients without significant stenosis, compared to the CG, implies that CAD could be related to 'adiponectin resistance'. Despite increased adiponectin, its protective effects could be diminished even in early stages of atherosclerosis.

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<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.

Factor analysis of risk variables associated with iron status in patients with coronary artery disease.

OBJECTIVES: Epidemiological evidence concerning the role of iron, a lipid peroxidation catalyst, in atherosclerosis and coronary artery disease (CAD) is inconsistent. DESIGN AND METHODS: Exploratory factor analysis was used to examine the potential clustering of variables known to be associated with CAD using data from 188 patients with angiographically-approved disease. The resulting factors were then tested for their association with serum ferritin and soluble transferrin receptor (sTfR) as indicators of body iron status. RESULTS: Factor analysis resulted in a reduction of a variable number from the original 15 to 5 composite clusters. These factors were interpreted as (1) "proatherogenic factor" with positive loadings of TC, LDL-C, apoB and TG; (2) "inflammatory factor" with positive loadings of hsCRP, fibrinogen and MDA; (3) "antiatherogenic factor" with positive loadings of HDL-C and apoA-I; (4) "obesity factor" with positive loadings of weight and waist; and (5) "antioxidative status factor" with positive loadings of SOD and age and negative loading of superoxide anion. "Inflammatory", "obesity" and "antiatherogenic" factors predicted high ferritin values and the "proatherogenic factor" predicted high sTfR values. We compared the ability of the "proatherogenic factor" with that of a multivariable logistic model that included the "proatherogenic factor" and sTfR values in predicting significant stenosis in patients. The area under the ROC curve was 0.692 vs. 0.821, respectively. CONCLUSIONS: "Inflammatory", "obesity", "antiatherogenic" and "proatherogenic" factors were associated with increased parameters of body iron status. The measurement of sTfR improves the prediction of CAD based on clustered cardiovascular risk factors.

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 <50% of obstruction had reduced mean HDL size and higher proportion of small HDL particles (P < 0.05). HDL size and proportion of small HDL particles were significant and independent predictors of obstructive CAD (P < 0.05, respectively). CONCLUSIONS: Stable angina patients with <50% of coronary obstruction have more favourable HDL subclasses distribution than patients with significant coronary stenosis.

Two rare conditions in an Eisenmenger patient: left main coronary artery compression and Ortner's syndrome due to pulmonary artery dilatation.

The left-main coronary artery extrinsic compression due to enlarged pulmonary artery has been described in several case series. Ortner's syndrome is also a rare condition in some cardiovascular disorders. There have been no reports about these two rare conditions in the same patient. Hence, we report a very rare case of an Eisenmenger patient with severe pulmonary hypertension and dilated pulmonary artery which has compressed the left main coronary artery, severely narrowing it, and the left laryngeal recurrent nerve with subsequent Ortner's syndrome and brief literature review.

[Intramural haematoma and penetrating aortic ulcer--outcome and treatment modalities: report of four cases].

INTRODUCTION: Intramural haematoma (IMH) and penetrating aortic ulcers (PAU) are the frequent cause of acute aortic syndrome that is disclosed with a rising frequency due to the development of new diagnostic methods. Different symptoms contribute to clinical misdiagnosis, while changeable locations and unpersuasive diameter can lead the radiologists to underestimate such changes. The outcome of PAU and IMH differs, and for the time being there are no data on prognostic factors. The diversity of symptoms and disease course is presented in four cases with different manifestations, treatment and outcome. OUTLINE OF CASES: Two patients with IMH were treated conservatively due to the process extensiveness and its morphology. One patient had a complete restitution, while the other had progression of the disease. Other two patients with PAU were treated by surgery (stent graft implantation) according to the morphology and diameter of the aorta. CONCLUSION: IMH and PAU should be suspected in patients with unclear clinical presentation (back and abdominal pains). Although outcome and complications of these diseases are well known, their incidence has not been fully studied. Endovascular treatment is less invasive and followed by a potentially lower rate of complications. However, usage of this method is justifiable only in patients with associated complications.

PON1 status is influenced by oxidative stress and inflammation in coronary heart disease patients.

OBJECTIVES: High-density lipoprotein (HDL) associated paraoxonase 1 (PON1) is an essential component of HDLs' capability to protect low-density lipoproteins (LDL) from oxidative modification and thus to limit the atherosclerotic process. The aim of the current study was to investigate the association between oxidative stress status, indices of inflammation and PON1 status parameters. DESIGN AND METHODS: We determined the relationship between the oxidative stress status, inflammatory markers and PON1 status parameters in 261 middle-aged subjects: 156 coronary heart disease (CHD) patients and 105 CHD-free subjects (as the control group). The PON1 status involved PON1 activity measurements towards two substrates: paraoxon (POase activity) and diazoxon (DZOase activity) and subsequent PON1(Q192R) activity phenotype determination. RESULTS: A statistically significant greater malondialdehyde (MDA) concentration in the RR phenotype subjects compared to QQ subjects within the CHD group was apparent (P<0.05). Multiple linear regression analysis revealed an independent influence of plasmatic SOD activity (P<0.05) on POase values and MDA (P<0.01) and O(2)(-) (P<0.05) on DZOase values. Involvement of inflammatory markers (fibrinogen and hsCRP) in the regression model did not hinder the influence of SOD and MDA on POase and DZOase activities, respectively. CONCLUSIONS: Our CHD patients were in a state of oxidative stress, which was most evident in the RR phenotype group. The QQ phenotype group is associated with the lowest oxidative stress status level and also with a better capacity for anti-oxidative protection. Oxidative stress in CHD patients is maintained by systemic low-grade inflammation, which results in PON1 enzymatic activity exhaustion. Therefore, deeper investigation of an effective anti-oxidative and anti-inflammatory therapy should be necessary in order to increase anti-oxidative potency and improve PON1 status of CHD patients.

Does simultaneous determination of LDL and HDL particle size improve prediction of coronary artery disease risk?

BACKGROUND: Alterations in plasma lipoprotein subclass distribution affect the risk for coronary artery disease (CAD). However, it is unclear whether the determination of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) phenotypes may or may not improve the ability to predict CAD development. METHODS: Polyacrylamide gradient (3-31%) gel electrophoresis was used to simultaneously determine size and distribution of lipoprotein subclasses in 181 CAD patients and 178 controls. RESULTS: Mean LDL and HDL subclass sizes were significantly smaller in patients than in controls (p < 0.001). Multivariate logistic regression analysis showed that small dense LDL particles were independent CAD risk predictors (OR = 2.867, p < 0.01), even when adjusted for other traditional risk factors, while small HDL particles lost their significance after adjustment (OR = 2.071, p = 0.054). The area under the ROC curve for LDL (0.671) and HDL (0.643) particle size measurement demonstrated low clinical accuracy when compared to the combination of traditional lipid risk factor measurements. CONCLUSIONS: CAD is associated with the predominance of smaller LDL and HDL particles. However, simultaneous determination of these two lipoprotein phenotypes provides no additional power in discriminating CAD and non-CAD subjects, beyond that obtained by the traditional risk factors.

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.

Correlation of oxidative stress parameters and inflammatory markers in coronary artery disease patients.

OBJECTIVES: In addition to many traditional risk factors for coronary artery disease (CAD) development, enhanced oxidative stress and inflammation are serious conditions that may also be classified as novel risk factors. In the present study, we assessed the relationship between several parameters of oxidative stress status [malonaldehyde (MDA), superoxide anion (O(2)(-)) and plasma and erythrocyte superoxide dismutase (SOD) activities] with high sensitivity C-reactive protein (hsCRP) and fibrinogen as inflammation markers. DESIGN AND METHODS: Oxidative stress status parameters, inflammation markers and lipid status parameters were measured in 385 subjects [188 coronary heart disease (CHD) patients with angiographically diagnosed coronary artery disease (CAD), 141 patients with occlusion >50% in at least one major coronary artery (CAD+) and 47 patients with occlusion less than 50% (CAD-), and 197 CHD-free middle-aged subjects (the control group)]. RESULTS: The plasma MDA concentration and the level of O(2)(-) in plasma were significantly higher in combination with significantly lower SOD activity in the CAD+ group vs. the control group. By using multiple stepwise regression analysis, fibrinogen and hsCRP showed independent correlation with MDA. Binary logistic regression analysis indicated that both MDA and O(2)(-) were significantly associated with CAD development and adjustment for inflammatory markers weakened this association in the case of MDA. CONCLUSIONS: The relationship between oxidative stress parameters and inflammatory species suggest their strong mutual involvement in atherosclerosis development that leads to CAD progression.

Paraoxonase-1 (PON1) activity, but not PON1(Q192R) phenotype, is a predictor of coronary artery disease in a middle-aged Serbian population.

BACKGROUND: Paraoxonase-1 (PON1) is a high-density lipoprotein (HDL)-associated serum enzyme that protects lipoproteins from oxidative modifications. Polymorphisms in the gene, including PON1Q192R, have been studied. However, inconsistencies regarding the above-mentioned polymorphism obscure its association with vascular disease. METHODS: Using a two-substrate (paraoxon/diazoxon) activity method, we investigated the frequencies of PON1Q192R phenotypes in 261 middle-aged subjects: 156 patients with angiographically assessed coronary heart disease (CHD) and 105 CHD-free subjects as the control group. The PON1(192) phenotype was predicted from examination of the two-dimensional plot of hydrolysis rates of diazoxon vs. paraoxon and by using the antimode of the histogram of the ratio of diazoxonase/paraoxonase activity. RESULTS: The PON1Q192R phenotype frequencies in 113 patients with occlusion >50% (coronary artery disease-positive, CAD+ group) vs. control population were as follows: QQ (0.552 vs. 0.510), QR (0.382 vs. 0.408) and RR (0.066 vs. 0.082); chi2=0.414, p=0.813. We found lower paraoxonase (POase) and diazoxonase (DZOase) activities in the CAD+ patients when compared to the control population. According to logistic regression analysis, POase activity was a better predictor of coronary disease onset compared with DZOase activity measurements and PON1Q192R phenotyping. CONCLUSIONS: We conclude that enzyme activity (within a particular phenotypic group) is more important than phenotype alone in predicting susceptibility to coronary artery disease.

Association of C-reactive protein with the presence and extent of angiographically verified coronary artery disease.

Prospective studies have demonstrated that markers of inflammation, such as high-sensitivity C-reactive protein (hsCRP) and fibrinogen, predict future cardiovascular disease risk. However, the association between the hsCRP and fibrinogen levels and the extent of coronary stenosis in patients with coronary artery disease (CAD) remains controversial. The aim of our case-control study was to assess the association of inflammatory markers with the occurrence and extent of CAD. Serum hsCRP and plasma fibrinogen levels were measured in 138 patients with angiographically assessed CAD and in 183 healthy subjects matched according to age and gender. According to the number of significantly stenosed (>or= 50%) vessels, the patients were classified in four groups: those without stenosis (0-vessel disease) and those with 1, 2 or 3-vessel disease. The hsCRP and fibrinogen levels were significantly higher in patients than in controls (p < 0.001). Although the hsCRP and fibrinogen levels tended to increase with the number of stenotic vessels, the differences were only significant for hsCRP (p < 0.01). Regression analysis indicated hsCRP as an independent predictor for the presence (OR = 3.573, p < 0.05) and extent of CAD (beta = 1.095, p < 0.05). In conclusion, the present study is the first report concerning the frequency distribution of hsCRP in Serbian healthy subjects and CAD patients. We have shown that elevated levels of hsCRP are associated with the presence and extent of CAD.

[Plasma and red blood cell superoxide dismutase activity in patients with different stages of essential hypertension]. / Aktivnost superoksid dizmutaze u plazmi i eritrocitima bolesnika sa razlicitim stadijumima esencijalne hipertenzije.

It has been suggested that superoxide dismutase (SOD) plays an important role in endothelial dysfunction in essential hypertension (EH), by competing with nitric oxide for superoxide, thus influencing nitric oxide bioavailability. To answer the question of whether endothelial dysfunction is consequence of altered SOD expression we determined SOD activity in patients with different stages of EH. In this study 45 EH patients and 25 normotensive subjects were included. EH patients were divided into the three groups according to the guidelines of European Society of Hypertension. SOD activity was determined spectrophotometrically in RBC and plasma of EH patients and controls. The results obtained have shown that all groups of EH patients exhibit lower SOD activity than control normotensive subjects. Significant correlation between SOD activity and both diastolic (p<0.05, r=-0.394) and systolic blood pressure (p<0.05, r=-0.356) was found. Lowering of SOD activity in patients with different stages of EH leads to inefficient detoxification of superoxide in EH. An excess of superoxide of both cellular and extracellular origin takes part in enhanced degradation of nitric oxide and altered vasodilation, and consequent endothelial dysfunction.