Mehmet Kanadaşı

Effects of apolipoprotein E genotypes and other risk factors on the development of coronary artery disease in Southern Turkey.

BACKGROUND Apolipoprotein E (apoE) plays a major role in lipoprotein metabolism and lipid transport. Associations between apoE genotypes, coronary artery disease (CAD) and other risk factors have been described by many investigators. The aim of this study was to investigate the role of apoE gene polymorphism and other risk factors in the development of CAD in subjects whose coronary arteries were evaluated by means of coronary angiography. METHODS The study population consisted of 199 subjects (114 male and 55 female). Of the total, 107 had CAD. The apoE gene was amplified by polymerase chain reaction (PCR) and then digested by CfoI restriction enzyme. The plasma lipid levels and other risk factors were also determined in all subjects. RESULTS The epsilon2 and epsilon4 allele frequencies and genotypes carrying epsilon4 allele were significantly higher in CAD (+) patients. Plasma lipids except triglycerides were increased in CAD (+) cases. We found that apoE genotypes, HT, DM, male gender, age and smoking were the independent predictors of CAD. There was no association between apoE alleles and lipids. CONCLUSION We conclude that apoE polymorphism (presence of epsilon4 allele) is associated with the development of CAD in Southern Turkey. In our study, we did not observe any effect of apoE alleles on lipid levels.

The distribution of circulating microRNA and their relation to coronary disease.

Background: MicroRNAs (miRNAs) are small RNAs that regulate gene expression by suppressing protein translation and may influence RNA expression. MicroRNAs are detected in extracellular locations such as plasma; however, the extent of miRNA expression in plasma its relation to cardiovascular disease is not clear and many clinical studies have utilized array-based platforms with poor reproducibility. Methods and Results: Initially, to define distribution of miRNA in human blood; whole blood, platelets, mononuclear cells, plasma, and serum from 5 normal individuals were screened for 852 miRNAs using high-throughput micro-fluidic quantitative RT-PCR (qRT-PCR). In total; 609, 448, 658, 147, and 178 miRNAs were found to be expressed in moderate to high levels in whole blood, platelets, mononuclear cells, plasma, and serum, respectively, with some miRNAs uniquely expressed. To determine the cardiovascular relevance of blood miRNA expression, plasma miRNA (n=852) levels were measured in 83 patients presenting for cardiac catheterization. Eight plasma miRNAs were found to have over 2-fold increased expression in patients with significant coronary disease (≥70% stenosis) as compared to those with minimal coronary disease (less than 70% stenosis) or normal coronary arteries. Expression of miR-494, miR-490-3p, and miR-769-3p were found to have significantly different levels of expression. Using a multivariable regression model including cardiovascular risk factors and medications, hsa-miR-769-3p was found to be significantly correlated with the presence of significant coronary atherosclerosis. Conclusions: This study utilized a superior high-throughput qRT-PCR based method and found that miRNAs are found to be widely expressed in human blood with differences expressed between cellular and extracellular fractions. Importantly, specific miRNAs from circulating plasma are associated with the presence of significant coronary disease.

The effect of early statin treatment on inflammation and cardiac events in acute coronary syndrome patients with low-density lipoprotein cholesterol.

We investigated the effects of atorvastatin on inflammation and cardiac events during the inpatient period and initial 6-month follow-up in acute coronary syndrome (ACS) patients with low low-density lipoprotein (LDL) cholesterol level. One hundred and twelve consecutive ACS patients with LDL cholesterol less than 100 mg/dl were included in the study (mean 78.2 ± 12.3 mg/dl). While 70 randomly selected patients received a dose of 40 mg atorvastatin within the first 24 h on top of their standard treatment as the atorvastatin group, the remaining 42 patients considered as the control group were given the standard treatment only, i.e., without any lipid-lowering drug therapy. Lipid profile, high-sensitivity C-reactive protein (hsCRP), and plasma amyloid A (SAA) levels were measured in all patients within the first 24 h of chest pain, on the 5th day, and in the 6th month. During the inpatient period and subsequent 6-month follow-up, all episodes of angina, reinfarction, revascularization, heart failure, rehospitalization, cardiac mortality, and total number of cardiac events were recorded. In the atorvastatin group, hsCRP and SAA values on the 5th day and in the 6th month compared to the first 24 h were significantly lower than those of the control group (P < 0.0001). Mean LDL cholesterol level was significantly decreased in the atorvastatin group (55.7 ± 17.7 mg/dl), but there was no significant change in the control group at the 6th month. The frequency of heart failure during the inpatient period and angina, unstable angina pectoris, heart failure, and revascularization in the first 6 months were also significantly reduced in the atorvastatin group. Atorvastatin started in the first 24 h reduces inflammation and improves the prognosis during both the inpatient period and the first 6 months of clinical follow-up in ACS patients with low LDL cholesterol levels.

Tissue doppler imaging and NT-proBNP levels show the early impairment of ventricular function in patients with beta-thalassaemia major.

ß-thalassaemia major is a chronic haemolytic anaemia, and congestive heart failure (CHF) is the most common cause of death in this disease. N terminal pro B type natriuretic peptide (NT-proBNP) increases with the severity of CHF and predicts the prognosis. The aim of this study was to investigate the relation between left ventricular systolic and diastolic function determined by standard pulsed wave Doppler (PWD), tissue Doppler imaging (TDI) and NT-proBNP in patients with ß-thalassaemia major. Thirty-four patients with ß-thalassaemia major and 34 healthy individuals were included in the study. Blood samples were taken for NT-proBNP. All patients and controls underwent echocardiographic examination. All cardiac chambers were significantly increased in the patient group. Left and right ventricular (LV, RV) ejection fractions and all diastolic parameters were normal in the patients and controls.Tissue Doppler imaging (TDI) showed a significant decrease in LV and RV Sm velocities in patients compared to the controls. NT-proBNP levels were also significantly higher in the patient group. There was a negative correlation between serum NT-proBNP levels and LV Sm and RV Sm velocities in patients (r=-0.426, P=0.006 and r=-0.409, P=0.009, respectively). Linear regression analysis showed that LV Sm and RV Sm were independent predictors for NT-proBNP. Our findings suggest that although iron overload in patients with ß-thalassaemia major impairs the systolic and diastolic functions of both ventricles, it impairs the systolic function earlier than diastolic function. Tissue Doppler imaging is an easy and reliable method in the early determination of ventricular dysfunction in these patients.

Frequency of diastolic dysfunction in patients with sickle cell anaemia : a tissue Doppler imaging study

Objective — Although cardiac dilatation and systolic dysfunction have been well documented as a late manifestation, there are conflicting reports regarding the diastolic dysfunction, by using traditional echocardiographic methods in patients with sickle cell anaemia (SCA).The aim of this study was to investigate left ventricular diastolic function in SCA patients without congestive heart failure by using pulsed wave tissue Doppler imaging (TDI). Methods — Thirty-one patients (18 men and 13 women, mean age: 26.4 ± 8.5 years) with homozygous SCA without congestive heart failure and 31 healthy control subjects (19 men and 12 women, mean age: 26.5 ± 7.6 years) were enrolled in the study. All patients and the controls underwent echocardiographic examination. Left ventricular diastolic function was evaluated by using both traditional pulsed wave Doppler (PWD) and TDI. Results —The cardiac chamber dimensions, wall thicknesses, E and A transmitral peak diastolic velocities, systolic (Sm), early (Em) and late (Am) diastolic myocardial velocities were significantly increased in the patients compared to the controls. Diastolic dysfunction was found in 7 (22.6%) and 3 (9.7%) patients by PWD and TDI, respectively. Of the 7 patients with diastolic abnormalities, 4 patients with a restrictive pattern by PWD were found to be normal by TDI. Conclusion — Our results show that left ventricular diastolic dysfunction is not a frequent finding in patients with SCA without congestive heart failure and TDI is a more reliable and easy method to evaluate diastolic function. Patients with a restrictive pattern found by PWD should be reevaluated by using TDI.

Cardiac troponin T as a prognostic marker in patients with heart failure : a 3-year outcome study.

Cardiac troponin T (cTnT), a highly sensitive and specific indicator of myocardial cell death, may be elevated in congestive heart failure (CHF). The aims of this study were to test the hypothesis that decompensated CHF may be associated with an increase in cTnT release and to correlate between cTnT levels and patient outcomes. The authors studied 55 patients aged between 38 and 86 years (30 women and 25 men) who were hospitalized for CHF. Left ventricular ejection fraction (EF) was calculated by using modified Simpsons rule by echocardiography. cTnT levels were assessed. Troponin T ≥0.1 ng/mL was considered as positive. All patients were contacted by phone annually during the next 3 years, and their history of subsequent hospital admissions and current health status were recorded. cTnT was negative in 44 (80%) and positive in 11 (20%) patients. EF was significantly lower and NYHA was higher in cTnT-positive patients. During the 3-year follow-up period, 25 patients died from CHF. The mortality rate was 8/11 (72.7%) among cTnT-positive patients, whereas the mortality rate was 17/44 (38.6%) among cTnT-negative patients. There were significant relationships among positivity of cTnT, NYHA, EF, and mortality rate. Multivariate regression analysis yielded an independent relationship between positivity of cTnT, NYHA classification, and mortality rate. The percent of hospital admissions due to CHF was also higher in patients with cTnT positive (63.6% versus, 27.3%, p <0.05). In conclusion, this study shows that cTnT positivity is an independent risk factor in predicting the long-term mortality and morbidity rate in patients with CHF. Patients with worsening CHF may possibly be identified early on the basis of their elevated serum cTnT levels.

The Presence of a Calcific Plaque in the Common Carotid Artery as a Predictor of Coronary Atherosclerosis

Many contradictory reports have been published investigating the relationship between coronary artery disease (CAD) and the increased intima-media thickness (IMT) in the common carotid artery (CCA). However, only a limited number of studies evaluate the relationship between CAD and CCA disease as reflected by both the plaque morphology (fibrous and calcific plaques) and IMT. We have studied the associations between CAD and the wall morphology of CCA by B-mode ultrasound (US). One hundred and forty-four subjects, whose angiography was planned on the basis of suspected CAD, were included into the study. The patients were divided into 4 groups on the basis of B-mode US findings; Group I: normal, Group II: increased IMT (IMT ≥ 0.8 mm and plaque absent), Group III: fibrous plaque, Group IV: calcific plaque. Coronary artery disease was diagnosed in 63 patients. A statistically significant correlation was found between CAD and CCA wall morphology (r =0.42, CI (95%) = 0.30-0.51, p<0.001). Positive predictive values were 45.0%, 48.4%, and 75.0% in patients with increased IMT, fibrous plaque, and calcific plaque, respectively. None of the women with normal CCA wall morphology had significant coronary artery lesion. With respect to the normal group, the risk for CAD increased by 4.3 fold with the existence of fibrous plaque (p=0.02) and by 9.9 fold with the existence of calcific plaque (p<0.001). It has been shown that the CCA wall morphology determined by B-mode US is correlated with CAD in patients with chest pain, and the presence of calcific plaque is a better predictor for CAD than that of fibrous plaque and increased IMT. Women with chest pain and normal CCA wall morphology may not need coronary angiography.

Left atrial appendage aneurysm presenting with recurrent embolic strokes

A case of left atrial appendage aneurysm is described in a 40-year-old man, who presented with recurrent embolic strokes and was asymptomatic until the last 6 months. Chest X-ray revealed a slightly prominent upper left heart border. The diagnosis was made by transthoracic two-dimensional echocardiography and confirmed by transesophageal echocardiography, magnetic resonance imaging and also by surgery.

Systolic Tissue Velocity Is a Useful Echocardiographic Parameter in Assessment of Left Atrial Appendage Function in Patients with Mitral Stenosis

Background: The incidence of thromboembolism remains high in patients with mitral stenosis (MS). The left atrial appendage (LAA) is a potential site for development of thrombus and LAA dysfunction is an independent predictor of thromboembolism. The LAA dysfunction is represented by reduced LAA late emptying velocity. But the magnitude of LAA flow velocities is dependent on acute changes in loading conditions. Aim: To investigate the value of the LAA tissue velocities obtained by tissue Doppler imaging (TDI) in assessment of LAA function in MS patients with and without thromboembolic events. Methods: The study population consisted of 98 isolated MS patients of 32 age and sex‐matched healthy controls. All subjects underwent transesophageal echocardiography (TEE). LAA late peak emptying (LAAEV) and filling (LAAFV) flow velocities were recorded. LAA peak late tissue systolic (LSV) and diastolic (LDV) tissue velocities by TDI were measured. The patients were divided into three groups as Group I (n = 38, sinus rhythm and LAAEV ≥ 25 cm/s), Group II (n = 26, sinus rhythm and LAAEV < 25 cm/s), and Group III (n = 34, atrial fibrillation). Results: Twenty‐one patients had thromboembolic events. LAAEV, LAAFV, LSV, and LDV were significantly reduced in patients with embolic events. Spontaneous echo contrast (SEC) density was strongly negative correlated with LSV, whereas weakly negative correlated with LAAEV. Multivariate regression analysis showed that LSV and the presence of SEC were independently associated with embolic events. Conclusion: LSV seems more reliable and useful parameter in evaluating LAA function. LAA function is more depressed among patients with embolic events.

Diastolic Function Predicts Outcome After Aortic Valve Replacement in Patients with Chronic Severe Aortic Regurgitation

Due to eccentric hypertrophy and fibrosis, patients with severe aortic regurgitation (AR) have diastolic dysfunction. Increased fibrosis correlates with increased myocardial stiffness and worsening of diastolic function. Patients with irreversible left ventricular (LV) dysfunction have severe myocardial fibrosis and myocyte apoptosis and do not benefit from aortic valve replacement (AVR).