Dimitra Kalimanovska-Ostric

Paraoxonase-1 (PON1) activity, but not PON1Q192R phenotype, is a predictor of coronary artery disease in a middle-aged Serbian population

Abstract 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 PON1192 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); χ2=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. Clin Chem Lab Med 2006;44:1206–13.

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

BackgroundAlterations 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.MethodsPolyacrylamide gradient (3–31%) gel electrophoresis was used to simultaneously determine size and distribution of lipoprotein subclasses in 181 CAD patients and 178 controls.ResultsMean 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.ConclusionsCAD 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.

Circulating Transforming Growth Factor-β1, Lipoprotein(a) and Cellular Adhesion Molecules in Angiographically Assessed Coronary Artery Disease

Abstract Transforming growth factor β1 (TGF-β1) is involved in different physiological and pathological processes, including atherogenesis. High plasma lipoprotein(a) (Lp(a)) concentration is an established independent risk factor that may interfere with the plasmin-mediated TGF-β1 activation. Both Lp(a) and TGF-β1 are thought to influence the expression of cellular adhesion molecules (CAMs), also involved in the process of atherogenesis. Whereas many studies confirmed the association between high plasma Lp(a) levels and coronary artery disease (CAD), conflicting results were obtained in different studies in which the changes of TGF-β1 and CAM concentrations in CAD patients were investigated. The aim of this case-control study was to explore the association of circulating TGF-β1, Lp(a) and CAMs (intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin) levels with the occurrence and severity of angiographically assessed coronary artery disease. Plasma TGF-β1, Lp(a), ICAM-1, VCAM-1 and E-selectin concentrations were measured in 100 patients with angiographically assessed CAD and 100 healthy blood donors matched according to age and gender. Lp(a) and TGF-β1 were significantly higher in patients than in healthy controls (p < 0.001 and p < 0.01, respectively), but no significant correlation between the TGF-β1 and Lp(a) values was found. The CAM concentrations obtained in CAD patients did not differ significantly as compared with the corresponding values in the controls. None of the measured parameters were influenced by the severity of CAD.

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.

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. Ortners 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 Ortners syndrome and brief literature review.

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 (R2 = 0.258; adjR2 = 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.

Association of adenylate cyclase‐associated protein 1 with coronary artery disease

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.

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.

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.

[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.