Ertugrul Ercan

Renin-angiotensin system gene polymorphisms and premature coronary heart disease

Introduction Experimental and clinical studies demonstrated that the renin-angiotensin system (RAS) affects the pathogenesis of atherosclerosis and prognosis of coronary heart disease (CHD). The aim of this study was to investigate the genotype distribution and the allele frequencies of three RAS genes polymorphisms and their effects on premature CHD in a Turkish population. Materials and methods One-hundred and fifteen Turkish patients with premature CHD and 128 controls were included into the study. Angiotensin-converting enzyme (ACE), angiotensin II type 1 (AT1) receptor and angiotensinogen (AGT) gene polymorphisms were analysed by polymerase chain reaction (PCR ) and restriction fragment length polymorphism (RFLP). Results The patients group showed an increased frequency of the ACE D allele compared with controls (65% vs. 35%, p=0.0001). There was a significant association between the DD genotype and premature CHD (ACE DD vs. ID and II; odds ratio [OR]=2.82 [CI 95% 1.33—2.91, p=0.002]). Also, we observed increased premature CHD risk associated with higher frequencies of the AGT MM genotype in patients when compared with controls (AGT MM vs. TT and MT, OR=1.92 [CI 95% 1.11—3.33, p=0.018]). We found a significant association between AT1-receptor AA genotype and decreased risk of premature CHD (AT1R AA vs. AC and CC, OR= 0.57[CI 95% 0.34—0.95, p=0.03]). Conclusions We demonstrated that increased premature CHD risk is associated with higher frequencies of the ACE DD and AGT MM genotypes. These findings indicate a synergistic contribution of ACE DD and AGT MM polymorphisms to the development of premature CHD. Also, our results suggest that family history, smoking, diabetes, hypertension, obesity and ACE DD genotype were independent risk factors for premature CHD.

Large atherosclerotic left main coronary aneurysm: a case report and review of literature

Left main coronary aneurysm is a very rare disorder. Aneurysm may be single or multiple, saccular or fusiform. Atherosclerosis, mucocutaneous lymph node syndrome, trauma, angioplasty, atheroctomy, laser procedures, systemic lupus erythematosus, periarteritis nodosa or types of arteritis, dissection, syphilis, mycotic emboli may lead to coronary aneurysms. The main complications of coronary aneurysms are: thrombosis, distal embolisation, rupture and calcification. Operative therapy should be necessary for large left main coronary aneurysms because of their predisposition to thrombosis and embolism. The coexisting significant obstructive CAD may be important in making a decision for the operative treatment in patients with the left main coronary aneurysm. The proper type of operation is not clear.

Myocardial infarction following a bee sting

We described here a patient envenomated by a bee sting that caused myocardial damage compatible with non-ST elevation acute myocardial infarction. She developed a typical course of myocardial infarction; the ECG changes were reversed to almost all normal limits. She had normal coronary angiography and reversible wall motion abnormalities. Myocardial damage following prolonged spasm in the coronary arteries may be the underlying factor.

High Inflammatory Activity Related to the Number of Metabolic Syndrome Components

J Clin Hypertens (Greenwich). 2010;12:136–144. ©2009 Wiley Periodicals, Inc.

Elevated serum CA 125 levels in mitral stenotic patients with heart failure.

Background: Elevated tumor marker levels have been reported in heart failure patients with left ventricular (LV) systolic dysfunction and enlargement. The levels of several tumor markers, including CA 125, CA 19-9, CA 15-3 and CEA, in rheumatic mitral stenotic patients were compared to the control group. Materials and Methods: Tumor markers were measured in 60 mitral stenotic patients and in 30 normal subjects who served as the control group. Mitral stenotic patients were classified into two categories of cardiac dysfunction based on the classification of the New York Heart Association (NYHA). Group I consisted of 31 patients in NYHA class 3–4 and group II of 29 patients in NYHA class 1–2. Echocardiographic examinations and invasive hemodynamic monitoring were performed in all patients. Results: Group I patients had decreased mitral valve area (p = 0.004) and higher left atrial diameter (p = 0.003) than group II patients. Right atrial, mean pulmonary artery and pulmonary capillary wedge pressures and transmitral gradient were higher in group I than in group II (p = 0.010, 0.0001, 0.0001 and 0.0001, respectively). CA 125 levels were statistically higher in mitral stenotic patient groups than in the control group (p < 0.0001). No statistically significant differences were shown for the other tumor markers. Group I patients had higher CA 125 levels compared to group II (p < 0.0001). Conclusion: Elevated CA 125 levels may be due to venous congestion and activation of peritoneal mesothelium or increased signal peptides.

Elevated levels of matrix metalloprotein-3 in patients with coronary aneurysm: A case control study

BackgroundMatrix metalloproteinases (MMPs) have been implicated in the pathogenesis of arterial aneurysms through increased proteolysis of extracellular matrix proteins. Increased proteolysis due to elevated matrix degrading enzyme activity in the arterial wall may act as a susceptibility factor for the development of coronary aneurysms. The aim of this study was to investigate the association between MMPs and presence of coronary aneurysms.MethodsThirty patients with aneurysmal coronary artery disease and stable angina were enrolled into study (Group 1). Fourteen coronary artery disease patients with stable angina were selected as control group (Group 2). MMP-1, MMP-3 and C-reactive protein (CRP) were measured in peripheral venous blood and matched between the groups.ResultsSerum MMP-3 level was higher in patients with aneurismal coronary artery disease compared to the control group (20.23 ± 14.68 vs 11.45 ± 6.55 ng/ml, p = 0.039). Serum MMP-1 (13.63 ± 7.73 vs 12.15 ± 6.27 ng/ml, p = 0.52) and CRP levels (4.78 ± 1.47 vs 4.05 ± 1.53 mg/l, p = 0.13) were not significantly different between the groups.ConclusionMMPs can cause arterial wall destruction. MMP-3 may play role in the pathogenesis of coronary aneurysm development through increased proteolysis of extracellular matrix proteins.

Prognostic value of plasma soluble CD40 ligand in patients with chronic non-valvular atrial fibrillation

AIMS We aimed to clarify whether determination of levels of soluble CD40 ligand (sCD40L) could predict subsequent thrombo-embolic events in patients with non-valvular atrial fibrillation (NVAF). METHODS AND RESULTS Forty-four consecutive outpatients (mean age: 58 +/- 6 years, 20 male) with chronic NVAF who were not receiving aspirin and had no thrombus or spontaneous echo contrast (SEC) on left atrium (LA) or left atrial appendage (LAA) were included in the study. The patients had no history of an embolic event and were followed up 24 +/- 2 months for thrombo-embolic events. sCD40L was determined at the enrollment. All patients were evaluated by means of SEC and thrombus formation by transoesophageal echocardiography at the end of follow-up period. Twelve (27%) patients had SEC and 2 (5%) patients had thrombus on LAA. Ischaemic stroke occurred in 2 (4.5%) patients and transient ischaemic attack developed in 4 (9%) patients during follow-up. sCD40L was significantly higher in patients with LASEC (0.41 +/- 0.05 vs. 0.16 +/- 0.04 ng/mL, P = 0.02) and embolic events (0.74 +/- 0.05 vs. 0.19 +/- 0.03 ng/mL, P = 0.001) than in those without. sCD40L levels were significantly related to the LASEC grade (R = 0.377, P = 0.02). In multivariable analysis, while independent variables for SEC or thrombus formation were LA diameter, sCD40L levels, and the duration of AF, independent variables for cerebrovascular events were the existence of SEC or thrombus formation on LAA, and sCD40L level. CONCLUSION Plasma sCD40L may prospectively predict stroke in AF. sCD40L may provide useful marker to identify patients at high thrombo-embolic risk with NVAF.

No association of interleukin-6 gene polymorphism (-174 G/C) with premature coronary artery disease in a Turkish cohort.

ObjectivesInterleukin-6 (IL-6) may contribute to the inflammatory response by activating endothelial cells and stimulating the synthesis of fibrinogen. It might thus be important in the pathogenesis of inflammation associated with coronary artery disease (CAD). Several studies suggested that the -174 C allele was associated with an increased prevalence of coronary heart disease. The aim of this study was to investigate further the association of the IL-6 -174 G/C allele status with premature CAD. MethodsA total of 120 patients and 105 controls were included in the study. The IL-6 -174 G/C polymorphism was genotyped using PCR–restriction fragment length polymorphism. ResultsThe genotype distribution of the -174 G/C polymorphism was not different in premature CAD patients (GG: 53%; GC: 42.6%; CC: 4.3%) and controls (GG: 54.3%; GC: 39%; CC: 6.7%) (P=0.72). The prevalence of the C allele was 25.6% in patients and 26.1% in controls. By multiple regression analysis, family history, smoking, diabetes, and hypertension were independent risk factors of premature CAD, but not IL-6 genotype. ConclusionsWe conclude that the IL-6 -174 G/C polymorphism is not associated with the risk of premature CAD, and does not contribute to cardiovascular risk stratification.

The effect of atorvastatin on platelet function in patients with coronary artery disease

Background — Lipid-lowering therapy was shown to have several beneficial effects in patients with coronary artery disease (CAD). Aim — The objective of this study was to investigate the effect of atorvastatin on platelet aggregation in patients with CAD. Methods — Twenty-five hypercholesterolaemic patients who had angiographically proven CAD and 16 normal subjects were enrolled. All patients received 10 mg/day atorvastatin for two months. Anti-platelet agents were discontinued 15 days prior to blood sampling at the beginning and at the end of the atorvastatin therapy. Aggregometric curves of the platelets in response to ADP, collagen and epinephrine were obtained using the aggregometry (turbidimetric) technique. Results — In patients with CAD, total cholesterol (TC) and LDL cholesterol (LDL-C) basal levels were measured (230 ± 49 mg/dl, 140 ± 41 mg/dl, respectively). Following lipid-lowering therapy, TC and LDL-C decreased significantly (p < 0.05). The activation measurements of aggregometric curves decreased significantly compared with basal parameters in response to ADP but not in response to collagen and epinephrine. Conclusion — Lipid-lowering therapy with the HMG-CoA reductase inhibitor, atorvastatin, had a marked reduction effect on platelet aggregation.

Polymorphisms of the methylenetetrahydrofolate reductase, vascular endothelial growth factor, endothelial nitric oxide synthase, monocyte chemoattractant protein-1 and apolipoprotein E genes are not associated with carotid intima-media thickness.

BACKGROUND Single nucleotide polymorphisms in the 5,10-methylenetetrahydrofolate reductase (MTHFR), vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), monocyte chemoattractant protein-1 (MCP-1) and apolipoprotein E (ApoE) genes appear to be a genetic risk factor for atherosclerosis. Common carotid intima-media thickness (cIMT) provides information on the severity of atherosclerosis. OBJECTIVE To investigate the relationship between cIMT and gene polymorphisms associated with atherosclerosis in Turkish patients with coronary artery disease (CAD). METHODS Sixty-two patients with angiographically diagnosed stable CAD were divided into two groups according to their cIMT values (group 1: n=35, cIMT of 1 mm or greater; group 2: n=27, cIMT of less than 1 mm). MTHFR 677 C/T, VEGF --460 C/T, eNOS 894 G/T, MCP-1 --2518 A/G and ApoE (E2, E3 and E4) gene polymorphisms (where A is adenine, C is cytosine, G is guanine and T is thymine) were analyzed by polymerase chain reaction and restriction fragment length polymorphism. Evaluations of cardiovascular risk factors and coronary atherosclerotic lesions were performed in all patients. Serum homocysteine and high-sensitivity C-reactive protein were measured and compared between the two groups. RESULTS Serum high-sensitivity C-reactive protein (P=0.04) and homocysteine (P=0.006) levels were higher in group 1 than in group 2. The ratio of multivessel CAD and previous myocardial infarction was significantly higher in group 1 than in group 2 (P=0.014). In the study population, no significant difference in cIMT was observed according to the polymorphisms studied. Only hyperhomocysteinemia (OR 1.17 [95% CI 1.01 to 1.35], P=0.033) and previous myocardial infarction (OR 3.76 [95% CI 1.10 to 12.81], P=0.034) maintained a significant correlation with cIMT on multiple logistic regression analysis. CONCLUSION cIMT is increased in patients with hyperhomocysteinemia, inflammation and extended CAD. MTHFR 677 C/T, VEGF --460 C/T, eNOS 894 G/T, MCP-1 --2518 A/G and ApoE single nucleotide polymorphisms were not associated with increased cIMT.