Harun Evrengul

Aortic Stiffness, Flow-Mediated Dilatation and Carotid Intima-Media Thickness in Obstructive Sleep Apnea

Background and Objective: Obstructive sleep apnea (OSA) has a critical association with cardiovascular mortality and morbidity. Carotid intima-media thickness (IMT), flow-mediated dilatation (FMD) and aortic stiffness are early signs of atherosclerosis. The presence of subclinical atherosclerosis was assessed in OSA patients using these parameters. Methods: 40 patients with OSA showing an apnea-hypopnea index (AHI) ≧5 (mean age 51.3 ± 9 years, 32 males) and 24 controls (AHI < 5, mean age 51.9 ± 5.2 years, 19 males) were enrolled in the study. In all subjects, polysomnographic examination and recordings were performed during sleep. IMT of the carotid artery, endothelium-dependent/-independent vasodilation of the brachial artery and aortic elastic parameters were investigated using high-resolution Doppler echocardiography. Results: The demographic data of the patients with OSA and controls were not significantly different. Subjects with OSA demonstrated higher values of aortic stiffness (7.1 ± 1.88 vs. 6.42 ± 1.56, respectively) and IMT (0.85 ± 0.13 vs. 0.63 ± 0.11 mm, p = 0.0001, respectively) but lower distensibility (9.47 ± 1.33 vs. 11.8 ± 3.36 cm2/dyn/106) and FMD (4.57 ± 1.3 vs. 6.34 ± 0.83%, p = 0.0001, respectively) than the controls. The respiratory disturbance index correlated positively with aortic stiffness and IMT and negatively with distensibility and FMD. Conclusion: We observed blunted endothelium-dependent dilatation, increased carotid IMT and aortic stiffness in patients with OSA compared with matched control subjects. This is evident in the absence of other diseases, suggesting that OSA is an independent cause of atherosclerosis. These simple and non-invasive methods help to detect subclinical atherosclerosis in OSA.

The effect of statin therapy on ventricular late potentials in acute myocardial infarction

AIMS To determine whether early statin therapy in acute myocardial infarction has any effect on ventricular late potentials which are considered as a noninvasive tool for evaluation of arrhythmogenic substrate. METHODS AND RESULTS Study population consisted of prospectively enrolled 72 patients presenting with acute myocardial infarction (<6 h). Thirty-four of the patients were randomized to pravastatin (40 mg/day) on admission irrespective of lipid levels. All patients received thrombolytic therapy. Signal-averaged ECG recordings were obtained serially prior to thrombolytic therapy, 48 h after and 10 days later. Late potentials were defined as positive if signal-averaged ECG met at least two of Gomes criteria: filtered total QRS duration >114 ms, root mean square voltage of the last 40 ms of the QRS <20 mV, or the duration of the terminal low (<40 mV) amplitude signals >38 ms. Changes observed in signal-averaged ECG recordings after thrombolysis were evaluated statistically with regard to statin usage. There were no significant differences between the clinical characteristics of the two randomized groups. There was a significant decrease in the rates of late potentials between the first and third signal-averaged ECG recordings after thrombolytic therapy in pravastatin group. Pravastatin group also had lower incidence of ventricular arrhythmias compared with control group (26 vs. 63%, P=0.021). The in-hospital cardiovascular event rates were also lower in statin group. CONCLUSION Early use of pravastatin reduces the incidence of late potentials following thrombolytic therapy in acute myocardial infarction. Statin therapy also seems to be reducing the incidence of in-hospital ventricular arrhythmias. These beneficial effects of statins might be explained through prevention of new myocardial ischemic episodes due to early plaque stabilization or regulation of endothelial and platelet functions.

Carotid intima-media thickness in coronary slow flow: relationship with plasma homocysteine levels.

Background and objectiveCoronary slow-flow phenomenon is characterized by delayed opacification of coronary vessels in a normal coronary angiogram. Although clinical and pathological features have been previously described, the underlying pathophysiology has not been fully elucidated. Thus, it still remains to be determined whether either microvascular or epicardial diffuse atherosclerotic disease is related to slow flow. In this study, we aimed to determine the carotid artery intima–media thickness, which is a marker of atherosclerosis in patients with coronary slow flow, and its possible relationship with the total homocysteine level. MethodThe study population consisted of 88 patients who underwent coronary angiography because of typical and quasi-typical symptoms of angina. Forty-four patients with angiographically proven coronary slow flow and 44 individuals with normal coronary flow pattern with similar risk profiles were enrolled in the study. Coronary flow patterns of the latter were determined by the thrombolysis in myocardial infarction frame count method. Intima–media thickness was measured by recording ultrasonographic images of both the left and the right common carotid artery with a 12-MHz linear array transducer. Plasma homocysteine, folate and B12 levels were measured from blood samples. ResultsPlasma homocysteine levels (μmol/l) and carotid intima–media thickness (mm) of patients with coronary slow flow were found to be significantly higher than that of controls (12.4±4.9 vs. 8.5±2.8, P=0.0001; 0.75±0.08 vs. 0.69±0.06, P=0.0001, respectively). The plasma folate level (ng/ml) was lower in coronary slow-flow patients than in controls (13.8±4.4 vs. 16.5±5.6, P=0.014). The plasma homocysteine level was significantly positively correlated with the mean thrombolysis in myocardial infarction frame count and intima–media thickness of the carotid artery in correlation analysis (r=0.58, P=0.0001; r=0.41, P=0.0001; respectively). ConclusionHomocysteine levels and carotid intima–media thickness increased but folate levels decreased in patients with coronary slow flow. The present findings allow us to conclude that the possible disturbance in the metabolism of homocysteine in patients with coronary slow flow may have a role in the etiopathogenesis of this phenomenon by causing generalized atherosclerosis.

Effect of Homocysteine-Induced Oxidative Stress on Endothelial Function in Coronary Slow-Flow

Background and Objective: Coronary slow-flow (CSF) phenomenon is characterized by delayed opacification of vessels in a normal coronary angiogram, but its etiopathogenesis remains unclear. Plasma homocysteine (Hcy) level can severely disturb vascular endothelial function and may play a role in the pathogenesis of CSF. In our study, endothelial function in patients with CSF and their relationship with Hcy and oxidative stress parameters are investigated. Method: Forty-four patients with angiographically proven CSF and 44 cases with normal coronary flow pattern with similar risk profile were enrolled in the study. Coronary flow patterns of the cases are determined by Thrombolysis in Myocardial Infarction (TIMI) frame count method. Endothelium dependent flow mediated dilatation (FMD) and independent vasodilatation characteristics are evaluated by high frequency ultrasound over the brachial artery. Superoxide dismutase (SOD) and reduced glutathione (GSH) and reduction of oxidative material in the body and the end product of lipid peroxidation, malondialdehyde (MDA) are measured as oxidative stress markers in blood samples. Results: Plasma Hcy level (µmol/l) of patients with CSF was found to be significantly higher than in controls (12.2 ± 4.9 vs. 8.5 ± 2.8, p = 0.0001). FMD was 7.87 ± 2.0% in controls and 4.98 ± 1.1% in patients with CSF (p = 0.0001). GSH was reduced in patients with CSF. SOD and MDA activity were found higher in patients with CSF than control subjects. Plasma Hcy level was significantly positively correlated with mean TIMI frame count and negatively correlated with FMD in correlation analysis (r = 0.58, p = 0.0001; r = –0.41, p = 0.022; respectively). Conclusion: The present findings allow us to conclude that patients with CSF have increased levels of Hcy and oxidative stress markers and impaired endothelial cell function.

Relation of insulin resistance and left ventricular function and structure in non-diabetic patients with essential hypertension

Objective — Both left ventricular hypertrophy and insulin resistance (IR) have often been demonstrated in patients with essential hypertension (EH). Insulin may exert a direct growth-promoting effect on cardiomyocytes.The purpose of this study was to examine the relationship between left ventricular structure, function and IR in patients with EH. Methods — We enrolled 73 patients (21 men, mean age 51.7 ± 9.2 years) with untreated hypertension (BP > 140 and/or 90 mm Hg, fasting glycaemia < 110 mg/dl) and 64 healthy subjects without diabetes mellitus and hypertension (21 men, mean age 48.9 ± 10.6 years) constituted the control group. In all subjects, transthoracic echocardiography was performed and blood samples were taken. Homeostasis model assessment (HOMA) was calculated by the formula: HOMA-index = fasting blood glucose (mg/dl) * immunoreactive insulin (mU/ml) /405 for the assessment of IR. Hypertensive patients were divided in two groups by mean HOMA index values. Each subject was examined for LV end-diastolic diameter, septal and posterior wall thickness, LV mass index (LVMI), fractional shortening (FS), mitral inflow velocity pattern, atrial filling fraction (AFF), left ventricular outflow velocity pattern and the total ejection isovolume index (TEI index). Results — The HOMA index (p < 0.001), LVMI (p < 0.001), AFF (p < 0.0001), peak A velocity (p < 0.028), septal (p < 0.0001) and posterior (p < 0.0001) wall thickness were significantly higher and FS (p < 0.001), E/A ratio (p < 0.0001) were significantly lower in hypertensive patients than healthy controls. LVMI (p < 0.01) and septal wall thickness (p < 0.001) were significantly higher in those hypertensive patients with a higher HOMA index.The HOMA-index was univariately related to the TEI index (r = 0.27, p = 0.01) and septal wall thickness (IVS) (r = 0.29, p = 0.01) by Pearson correlation analysis in hypertensive patients. LVMI, FS and mitral inflow velocity pattern were not related to the HOMA index. The TEI index (R2 = 0.20, p = 0.0001) and IVS (R2 = 0.12, p = 0.002) were significantly related to the HOMA-index as an independent variable by stepwise regression analysis Conclusions — These results demonstrated that hypertensive patients had both abnormal cardiac structure and function and higher IR index. In our study group, the effect of hypertension on cardiac structure and function was correlated with IR. Our results suggested that IR might be an important factor causing left ventricular dysfunction and wall thickness in non-diabetic patients with EH.

Preservation of pleural integrity in patients undergoing coronary artery bypass grafting: effect on postoperative bleeding and respiratory function.

Objective —The purpose of this study was to evaluate the influence of preserved integrity of pleura on postoperative bleeding and respiratory function in patients undergoing coronary artery bypass grafting (CABG). Methods and results — Seventy-two CABG patients who received pedunculated IMA graft without opening the pleura (group of intact pleura, group IP) between July 2002 and September 2004 were matched to 72 CABG patients who received pedunculated IMA graft with opened pleura (group of opened pleura, group OP).To match the patients with IP and unique patients with OP, logistic regression was used to develop a propensity score. The C statistic for this model was 0.79. Patients with IP were matched to unique patients with OP with an identical 5-digit propensity score. If this could not be done, we proceeded to a 4-, 3-, 2-, or 1-digit match. Patients characteristics were well matched. There were no differences in preoperative and peroperative variables between the groups. The incidence of postoperative pleural effusion and thoracentesis were significantly lower in group IP than group OP (pleural effusion in 15.2 versus 30.5%; p = 0.029, thoracentesis in 5.5 versus 18.5%; p = 0.036). Other pulmonary complications such as prolonged ventilation, reintubation, pneumothorax, atelectasis, diaphragmatic paralysis were similar in both groups. Patients with IP had significantly lower blood loss (520 versus 870 ml; p < 0.001) and whole blood unit transfusion (26.3 versus 41.6%, p = 0.036). Also, intensive care unit and hospital stay were similar in both groups. Conclusions — Meticulous internal mammary artery harvesting and preservation of the pleural integrity significantly reduces postoperative bleeding and pleural effusion.

QT dispersion and left ventricular hypertrophy in athletes: relationship with angiotensin-converting enzyme I/D polymorphism.

Background — QT dispersion (QTd) is a measure of inhomogeneous repolarization of myocardium and is used as an indicator of arrhythmogenicity. QTd is increased in myocardial hypertrophy secondary to systemic hypertension. The relation between left ventricular (LV) enlargement in endurance trained subjects and QTd is unknown.The cloning of the angiotensin-converting enzyme (ACE) gene has made it possible to identify a deletion (D)-insertion (I) polymorphism that appears to affect the level of serum ACE activity. The aim of this study was to assess whether physiologic left ventricular hypertrophy as a result of physical training is associated with an increased QT length or dispersion depending on ACE I/D polymorphism. Methods — 56 endurance athletes and 46 sedentary subjects were included in this study, and they underwent both complete echocardiographic and electrocardiographic examination, the QT interval was measured manually as an average based on a 12-lead ECG.We also analysed ACE I and D allele frequencies in all patients. Results — Athletes had a significantly increased LV mass (235.1 ± 68.5 g vs.144.9 ± 44.5 g, p < 0.001) and corrected QTd (QTcd) (55.5 ± 18.1 ms vs. 42.9 ± 17.2 ms, p < 0.001) in comparison to control subjects.There was a positive correlation between left ventricular mass index and QTcd in athletes (r = 0.3, p = 0.024). Left ventricular mass and mass index in ACE DD, DI and II genotypes were significantly different (p < 0.001). QTcd was significantly different between ACE DD (63.2 ± 12.8 ms) and ACE II (44.9 ± 17.6 ms) genotypes in athletes (p < 0.05). Conclusion — These data show that myocardial hypertrophy induced by exercise training might be associated with increased QTd as observed in systemic hypertension and might be affected by ACE I/D polymorphism.

Effects of Angiotensin-Converting Enzyme Polymorphism on Aortic Elastic Parameters in Athletes

Background: Physiologic adaptations in an athlete’s heart include increased left and right ventricular chamber size, left ventricular wall thickness and mass. Angiotensin-converting enzyme (ACE) is a key enzyme in angiotensin II production causing cardiac hypertrophy. The cloning of the ACE gene has made it possible to identifya deletion (D)-insertion (I) polymorphism that appears to affect the level of serum ACE activity. Therefore, the ACE genes, which have been shown to be polymorphic, could be candidate genes for large-artery stiffness. Methods: 56 endurance athletes and 46 sedentary subjects were included in this study, and they underwent both complete echocardiographic examination, and analysis of ACE insertion (I) and deletion (D) allele frequencies in peripheral blood. The aortic diameter was recorded by M-mode echocardiography at a level 3 cm above the aortic valve. Aortic systolic diameter was measured at the time of full opening of the aortic valve, and diastolic diameter was measured at the peak of QRS. Aortic strain, stiffness index and distensibility were calculated. Results: Left ventricular mass index and left ventricular ejection fraction were significantly higher in athletes than controls (p < 0.001). The aortic distensibility index and strain were significantly greater in athletes compared with controls (respectively: 5.8 ± 2.7 vs. 4.7 ± 1.8 cm–2 dyn–1 10–6, p = 0.017; 12.3 ± 2.4 vs. 9.3 ± 3.1, p < 0.001). The aortic stiffness index was significantly lower in athletes than in controls (4.8 ± 1.9 vs. 6.1 ± 2.1, p < 0.001). The aortic distensibility index and strain were statistically different in ACE DD vs. DI groups and DD vs. II groups of athletes. The aortic stiffness index was statistically different in ACE DD vs. II groups of athletes. Aortic parameters were similar according to ACE genotypes in controls. Conclusion: The results of this study indicate that aortic distensibility was increased by prolonged training in endurance athletes, particularly in those with the ACE II genotype. This effect represents an extracardiac adaptation to chronic prolonged training in athletes.

The antiarrhythmic effect and clinical consequences of ischemic preconditioning.

Potentially hazardous short ischemic episodes increase the tolerance of myocardium to ischemia paradoxically. This condition decreases the infarct area markedly caused by a longer duration of coronary occlusion. This phenomenon is known as ‘ischemic preconditioning’ and its powerful cardioprotective effect has been shown in experimental and clinical studies. Ischemic preconditioning decreases cardiac mortality markedly by preventing the development of left ventricular dysfunction and ventricular and supraventricular arrhythmias after acute myocardial infarction. Ischemia-induced opening of ATP-sensitive potassium channels and synthesis of stress proteins via activation of adenosine, bradykinin and prostaglandin receptors seem to be the possible mechanisms. By understanding the underlying mechanisms of ischemic preconditioning, it may be possible to develop new pharmacologic agents that cause ischemic preconditioning with antiischemic and antiarrhythmic properties without causing myocardial ischemia.

Interaction of Plasma Homocysteine and Thyroid Hormone Concentrations in the Pathogenesis of the Slow Coronary Flow Phenomenon

Background and Objective: The slow coronary flow (SCF) phenomenon is an angiographic observation and a well-recognized clinical entity characterized by delayed opacification of vessels in a normal coronary angiogram due to reasons yet unclear. Thyroid hormones exert significant effects on plasma homocysteine (Hcy) levels and microvascular resistance. Recently, several investigators have consistently reported that elevation of the plasma Hcy level can severely disturb vascular endothelial function and play a role in the pathogenesis of SCF. Accordingly, we investigated the levels of plasma Hcy and thyroid hormones and their relationship in patients with SCF. Method: Forty-four patients with angiographically proven SCF (Group I) (mean age 55.5 ± 10.4 years, 26 males) and 44 cases with normal coronary flow (NCF) pattern (Group II) (mean age 53.9 ± 11 years, 22 males) with similar risk profiles were enrolled in the study. Coronary flow patterns of the cases were determined by the thrombolysis in myocardial infarction (TIMI) frame count method. The coronary TIMI frame counts were calculated separately for each coronary artery and their average was determined as the mean TIMI frame count for each subject. Serum levels of free tri-iodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH) and Hcy were measured. Patients with thyroid disease or on medications with a potential to affect thyroid functions were excluded. Results: There were no statistically significant differences between the groups concerning the demographic characteristics and major cardiovascular risk factors. Mean TIMI frame counts of SCF and NCF groups were 45.9 ± 12 and 23.3 ± 3.7, respectively. fT4 (ng/dl) and TSH (µIU/ml) levels of the two groups were similar (p > 0.05). The level of fT3, the active metabolite of the thyroid hormone family, was dramatically reduced in the SCF group when compared to the NCF group (2.3 ± 0.2 vs. 3.0 ± 0.3, p = 0.0001, respectively). Plasma Hcy levels of patients with SCF were found to be significantly higher than controls (12.2 ± 4.9 vs. 8.5 ± 2.9, p = 0.0001, respectively). Correlation analysis showed a significant negative correlation between the plasma fT3 and Hcy levels and the mean TIMI frame counts (r = –0.31, p = 0.003 vs. r = –0.66, p = 0.0001). Moreover, there was a significant positive correlation between the plasma Hcy levels and the mean TIMI frame counts (r = 0.58, p = 0.0001). Also, fT3 was the only significant determinant of the variance of Hcy in multiple regression analysis (r = –0.30, p = 0.005). Conclusion: fT3 levels were decreased and plasma Hcy levels were increased significantly in patients with SCF as compared to controls. This finding suggests that thyroid hormones and/or (?) a possible disturbance in their metabolism may be responsible for the elevated levels of plasma Hcy in patients with SCF and may play a role in the pathogenesis of the SCF phenomenon.