Aycan Fahri Erkan

Lack of Association Between Matrix Metalloproteinase-9 and Endothelial Nitric Oxide Synthase Gene Polymorphisms and Coronary Artery Disease in Turkish Population

Polymorphic variants of genes encoding proteins involved in vascular remodeling may genetically diverge among different populations and play a role in the susceptibility to the coronary artery disease (CAD). MMP-9-1562 C/T (rs3918242), eNOS T-786C (rs2070744), and Glu298Asp (rs1799983) are among the most studied of these polymorphisms. The aim of this study was to determine the relationship between CAD and these polymorphisms in the Turkish population. The analysis included 146 CAD+ and 122 CAD- individuals. Genomic DNA was isolated from whole blood and genotyping was performed by the PCR-RFLP method. No significant associations were found between -1562 C/T (p = 0.557), Glu298Asp (p = 0.432), and -786 T/C (p = 0.055) polymorphisms and CAD. The distribution of each haplotype also did not differ between CAD+ and the CAD- samples (p > 0.05). The present investigation is the first to study an association between -1562 C/T polymorphism and CAD in the Turkish population. In conclusion, no appreciable differences between CAD+ and CAD- samples were found in terms of polymorphisms mentioned above.

Neutrophil to lymphocyte ratio is associated with more extensive, severe and complex coronary artery disease and impaired myocardial perfusion

OBJECTIVES We investigated the relation between neutrophil to lymphocyte ratio (N/L) and the extent, severity, and complexity of coronary artery disease (CAD) and myocardial perfusion. STUDY DESIGN One hundred and fifty-one patients who underwent coronary angiography with stable angina pectoris (SAP) (n=93) or acute coronary syndrome (ACS) (n=58) were included in the study. Blood samples were drawn before coronary angiography. Gensini and SYNTAX scores and myocardial blush grade (MBG) were assessed. RESULTS Neutrophil counts were 4.4±1.4 and 5.0±1.6 in the SAP and ACS groups (p=0.018), whereas lymphocyte counts were 2.2±0.7 and 2.1±0.7, respectively (p=0.104). N/L was 2.2±1.2 in the SAP and 2.6±1.0 in the ACS (p=0.002) groups. In patients with SAP, N/L was significantly correlated with Gensini and SYNTAX scores (Gensini score r=0.32, p=0.002; SYNTAX score r=0.36, p=0.000), but there was no significant correlation between N/L and MBG. In the ACS group, N/L had a more powerful association with both Gensini and SYNTAX scores (Gensini r=0.42, p=0.001; SYNTAX r=0.51, p=0.000). N/L was negatively correlated with MBG in ACS patients (r= -0.48, p=0.000). Significant correlations persisted both in the SAP and ACS groups after correcting for age, diabetes, hyperlipidemia, and statin use; however, the associations were weaker. Cut-off N/L to predict moderate to severe CAD according to SYNTAX score was 2.26, with 72% sensitivity and 71% specificity (area under the curve [AUC]: 0.772, 95% confidence interval [CI] 0.679-0.865, p<0.001). CONCLUSION N/L is associated with severe, extensive and complex CAD and may be used to predict moderate to severe involvement in patients with CAD.

The Relationship of the ESR1Gene Polymorphisms with the Presence of Coronary Artery Disease Determined by Coronary Angiography

Effects of estrogen on the cardiovascular system, mediated mainly by estrogen receptor type alpha (ER alpha), have been well-defined and specific polymorphisms in the ER alpha gene (ESR1) have been associated with several coronary heart diseases including coronary artery disease (CAD) in studies covering different populations. In the present study, we aimed to investigate whether there is an association between two of the known polymorphisms in the ESR1, named c.454-397T>C and c.454-351A>G, and CAD in a Turkish population. One hundred sixty eight patients with CAD and 99 patients without CAD were included in the study. The ESR1 c.454-397T>C and c.454-351A>G polymorphisms were studied by the conventional polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. While no association was found between the c.454-351A>G polymorphism and CAD, the c.454-397T>C genotype distributions were statistically significant independent of known risk factors between CAD-positive (CAD+) and CAD-negative (CAD-) groups (p = 0.001). TT genotype was more frequent in CAD- group than in CAD+ group, 22.2% and 4.8%, respectively. CC genotype was associated with increased risk of CAD (p = 0.001) compared to the TT genotype. When comparing the distribution of CC + TC genotypes to that of TT genotype in CAD+ and CAD- groups, the frequency of CC + TC genotypes showed a significant increase independent of known CAD risk factors in CAD+ subjects (p = 0.001). As a conclusion, a statistically significant relationship between the ESR1 c.454-397T>C polymorphism and CAD were found independent of known CAD risk factors in a Turkish population.

Epicardial adipose tissue thickness can be used to predict major adverse cardiac events.

ObjectiveIncrease in epicardial adipose tissue (EAT) thickness is associated with subclinical and manifest coronary artery disease. In addition, it is associated with the severity and extent of coronary atherosclerosis. We aimed to investigate whether increased EAT thickness is associated with adverse cardiovascular outcomes. Patients and methodsTwo hundred consecutive patients who were admitted with stable angina pectoris, unstable angina pectoris or acute myocardial infarction (MI), and had undergone coronary angiography were included and followed for revascularization, nonfatal MI, hospitalization for heart failure and cardiovascular death for 26 (5–30) months. ResultsThere were significantly more revascularizations, nonfatal MI and cardiovascular death in patients with an initial EAT thickness more than 7 mm (P<0.001 for all). Significant predictors of cardiovascular death were identified as an EAT thickness more than 7 mm [hazard ratio (HR) 1.9, 95% confidence interval (CI) 0.4–8.3, P=0.039] and diabetes (HR 3.42, 95% CI 0.7–17.5, P=0.014) in the multivariate Cox regression analysis. Event-free survival for cardiovascular death in the EAT up to 7 mm group was 97.9%, whereas it was 90.7% in the EAT more than 7 mm group (P=0.021). In addition, significant predictors of MI were identified as an EAT thickness more than 7 mm (HR 2.4, 95% CI 0.6–10.0, P=0.021) and diabetes (HR 3.4, 95% CI 1.0–11.2, P=0.04). Event-free survival for MI in the EAT up to 7 mm group was 96.4%, whereas it was 68.2% in the EAT more than 7 mm group (P=0.001). ConclusionIncrease in EAT thickness independently predicts adverse cardiac events including MI and cardiovascular death.

Epicardial adipose tissue thickness is associated with myocardial infarction and impaired coronary perfusion.

Objective: Epicardial adipose tissue (EAT) is associated with the presence, severity and extent of atherosclerotic coronary artery disease (CAD) in addition to subclinical atherosclerosis. We investigated if EAT thickness is related to acute myocardial infarction in patients with CAD. We also searched for the association between EAT thickness and objective coronary flow and myocardial perfusion parameters such as Thrombolysis in Myocardial Infarction Frame count (TFC) and myocardial blush grade (MBG). Methods: Two-hundred consecutive patients with stable angina pectoris or acute coronary syndrome who were admitted to Ufuk University Faculty of Medicine, Dr Ridvan Ege Hospital cardiology department were included in this observational, cross-sectional study. EAT thickness was evaluated by conventional transthoracic echocardiography. Coronary angiography was performed to determine the coronary involvement and perfusion. Results: Mean EAT thicknesses were 5.4±1.9 mm, 6.3±1.8 mm, and 8.5±1.4 mm in the stable angina pectoris (SAP), unstable angina pectoris (USAP) and acute myocardial infarction groups, respectively (p<0.001). With increasing EAT thickness, TFC increases whereas mean MBG values decrease (for EAT thickness <5 mm, 5-7 mm, >7 mm; mean TFC: 21.6±2.2, 25.3±3.3 and 35.2±7.7; and MBG values: 2.98±0.14, 2.83±0.57 and 1.7±1.16, respectively; both p<0.001). Cut-off EAT value to predict AMI was identified as 7.8 mm (ROC analysis AUC: 0.876; p<0.001, 95% CI: 0.822-0.927). Sensitivity and specificity of EAT cut-off value 7.8 mm to predict AMI were 81.8% and 82.5% respectively. Conclusion: Increased EAT is associated with AMI and it may prove beneficial for choosing patients who would need more aggressive approach in terms of risk reduction using echocardiography which is a relatively cheap and readily available tool as a follow-up parameter.

Arterial stiffness and central arterial wave reflection are associated with serum uric acid, total bilirubin, and neutrophil-to-lymphocyte ratio in patients with coronary artery disease.

Objective Total bilirubin (TB) was recently recognized as an endogenous anti-inflammatory and anti-oxidant molecule. Uric acid (UA) takes part in cardiovascular diseases by inducing oxidative stress, inflammation, and endothelial dysfunction. We assessed the relationship between serum TB levels, serum UA levels, and inflammatory status assessed by neutrophil-to-lymphocyte ratio (N/L) and arterial stiffness and arterial wave reflection in patients with a clinical diagnosis of coronary artery disease (CAD). Methods We included 145 consecutive patients admitted with stable angina pectoris (SAP) or acute coronary syndrome (ACS). Blood samples were drawn at admission for complete blood count and biochemistry. Non-invasive pulse waveform analysis for the determination of augmentation index (AIx) and carotid-femoral pulse wave velocity (PWV) measurements were performed with the commercially available SphygmoCor system. Results When patients were divided into tertiles of PWV and AIx, median N/L and median serum UA levels were the highest and mean TB levels were the lowest in the third tertile (p<0.001 for all). AIx and PWV were positively associated with serum UA and N/L and negatively associated with serum TB levels (p<0.001 for all). After adjustments for age, gender, heart rate, systolic blood pressure, and presence of diabetes, significant correlations persisted for N/L, UA, and TB in ACS patients (p<0.05). In the SAP group, TB was significantly negatively correlated with AIx and PWV, and UA was significantly positively correlated with PWV (p<0.05). Conclusion N/L ratio and serum UA and TB levels might be used to risk-stratify patients with respect to arterial stiffness in CAD patients, especially in the presence of ACS.

Epicardial Adipose Tissue Thickness Is an Independent Predictor of Critical and Complex Coronary Artery Disease by Gensini and Syntax Scores

Epicardial adipose tissue thickness is associated with the severity and extent of atherosclerotic coronary artery disease. We prospectively investigated whether epicardial adipose tissue thickness is related to coronary artery disease extent and complexity as denoted by Gensini and Syntax scores, and whether the thickness predicts critical disease. After performing coronary angiography in 183 patients who had angina or acute myocardial infarction, we divided them into 3 groups: normal coronary arteries, noncritical disease (≥1 coronary lesion with <70% stenosis), and critical disease (≥1 coronary lesion with <70% stenosis). We used transthoracic echocardiography to measure epicardial adipose tissue thickness, then calculated Gensini and Syntax scores by reviewing the angiograms. Mean thicknesses were 4.3 ± 0.9, 5.2 ± 1.5, and 7.5 ± 1.9 mm in patients with normal coronary arteries, noncritical disease, and critical disease, respectively (P <0.001). At progressive thicknesses (<5, 5-7, and >7 mm), mean Gensini scores were 4.1 ± 5.5, 19.8 ± 15.6, and 64.9 ± 32.4, and mean Syntax scores were 4.7 ± 5.9, 16.6 ± 8.5, and 31.7 ± 8.7, respectively (both P <0.001). Thickness had strong and positive correlations with both scores (Gensini, r =0.82, P <0.001; and Syntax, r =0.825, P <0.001). The cutoff thickness value to predict critical disease was 5.75 mm (area under the curve, 0.875; 95% confidence interval, 0.825-0.926; P <0.001). Epicardial adipose tissue thickness is independently related to coronary artery disease extent and complexity as denoted by Gensini and Syntax scores, and it predicts critical coronary artery disease.

Successful Management of Coronary Artery Rupture with Stent-Graft: A Case Report

Perforation of coronary arteries is a relatively rare yet life-threatening complication of percutaneus coronary interventions and is encountered in approximately 0.5% of these procedures. According to the type of coronary perforation, various methods of correction are employed, ranging from conservative approach to emergency cardiac surgery. Coronary stent-grafts are composed of two metal stents and a polytetrafluoroethylene layer between them. Advent of such stents enabled efficient endovascular repair of coronary artery perforation. We present a case of coronary artery perforation which had occurred during stent implantation for the treatment of a bridged segment in the distal portion of the left anterior descending artery. This perforation was successfully managed by implanting a stent-graft.

The effect of clopidogrel on apoptosis--an in vivo study.

Clopidogrel is widely used in cardiovascular medicine, and is believed to play an important role in the pathogenesis of many cardiovascular disease processes. In particular, patients undergoing coronary stenting, who are commonly treated with clopidogrel, are candidates for in‐stent restenosis. This is mainly caused by neointimal hyperplasia, so it is important to consider whether clopidogrel affects neointimal hyperplasia via apoptosis. Lymphocytes, especially T‐cells, are known to play a key role in the initiation and formation of atherosclerotic plaques. The aim of this study was to investigate the effect of clopidogrel on human lymphocyte apoptosis, using a DNA fragmentation assay.