Dilek Cicek

Slow coronary flow may be a sign of diffuse atherosclerosis. Contribution of FFR and IVUS.

Objective. — Slow coronary flow (SCF) is a phenomenon characterized by delayed opacification of coronary arteries in the absence of epicardial occlusive disease, in which many aetiological factors such as microvascular and endothelial dysfunction, and small vessel disease have been implicated. We aimed to investigate the epicardial resistance in relation with SCF by using fractional flow reserve (FFR) and intravascular ultrasound (IVUS). Both have been combined to disclose the related epicardial flow resistance and the arterial anatomy. Methods and results. — Coronary pressure and FFR measurement were performed in 19 (8 (42.1%) men, 11 (57.9%) women; age = 55.9 ± 9.4 years) patients with SCF. All patients underwent subsequent IVUS investigation at the same setting. As compared with expected normal values, FFR values were significantly lower (1.0 vs. 0.83 ± 0.13, p < 0.0001). In patients with SCF, a strong negative correlation was seen between TIMI frame count and FFR (r = –0.551, p < 0.05). Upon IVUS investigation, the common finding was longitudinally extended massive calcification throughout the epicardial arteries and increased intimal thickness (0.59 ± 0.18mm). A negative correlation between intimal thickness and FFR was determined (r = –467, p < 0.05). Conclusion. — We have demonstrated the decreased FFR in the patients with SCF. Decreased FFR levels have been attributed to increased resistance in the epicardial coronary arteries due to diffuse atherosclerotic disease which has been demonstrated by IVUS.

Glutathione S-transferase gene polymorphism as a susceptibility factor in smoking-related coronary artery disease

Abstract.Coronary artery disease (CAD) is the leading cause of morbidity and mortality in the world, and cigarette smoking is a major contributing factor to the disease. Glutathione S-transferase (GST) enzyme is implicated in the detoxification of carcinogens present in tobacco smoke and consequent polymorphisms in this gene may confer susceptibility to cardiovascular disease if DNA damage is important in CAD. Therefore, we examined this question in a case-control study of subjects having coronary atheroma by angiography and with a past history of myocardial infarction (MI). The study population consists of 247 healthy controls and 148 consecutive patients who had undergone coronary angiography for suspicion of coronary artery disease. DNA was extracted from whole blood, and the GSTM1 and GSTT1 polymorphisms were determined using a real-time polymerase chain reaction (PCR). We found that the null GSTM1 and GSTT1 genotypes were associated with an increase in the risk of developing coronary heart disease (OR = 1.14; 95% CI: 0.71 – 1.82; OR = 1.38; 95% CI: 0.82 – 2.32), respectively, but this increase was not significant. Patients who smoke having the null genotypes of GSTM1 (OR: 1.63 (1.10 – 2.63)) and GSTT1 (2.66 (1.50 – 4.72)) and both (3.20 (1.37 – 7.45)) were at a higher risk for developing coronary heart disease. In conclusion, the finding of a significant association between GSTM1 and T1 with smoking status may influence cardiovascular disease via DNA damage.

Metoprolol, a Β-1 selective blocker, can be used safely in coronary artery disease patients with chronic obstructive pulmonary disease

The coexistence of coronary artery disease (CAD) and chronic obstructive pulmonary disease (COPD) is frequent because of common etiological factors. Β-Blockers remain underutilized in patients with CAD who also have COPD. This study was performed to evaluate the safety of Β-1 selective blocker agents in CAD patients with COPD. Fifty patients (aged 57.3 ± 10.1 years) were enrolled in this study; 27 patients received metoprolol CR (controlled release), and 23 received metoprolol (conventional). The patients were stratified according to the severity of COPD (21 severe, 21 moderate, and 8 mild), started on metoprolol CR or conventional metoprolol, and titrated up to the maximum tolerated dose. The clinical controls were done during the first week and then at the first and third month. Patients received a mean total daily dose of 92.5 ± 18 mg of metoprolol CR or 189 ± 36.7 mg of metoprolol. Seven patients could not receive the maximum dose. There was no significant decrease in forced expiratory volume in 1 s (FEV1) in either group (basal vs last FEV1: 54.5% ± 13.4% vs 54.3% ± 13% in the metoprolol CR group and 49.6% ± 14.5% vs 53.2% ± 12.8% in the metoprolol group). No adverse event was experienced. Metoprolol, a Β-1 selective blocker, can be used safely at the maximum dose in CAD patients with COPD.

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 Relationship between Plasma Endothelin-1, Nitric Oxide Levels, and Heart Rate Variability in Patients with Coronary Slow Flow

Background: Coronary slow flow (CSF) is characterized by delayed opacification of coronary arteries in the absence of epicardial occlusive disease. In this study, we aimed to determine endothelin‐1 (ET‐1), nitric oxide (NOx) levels and time domain heart rate variability (HRV) parameters in patients with CSF and relationship among these parameters.

The correlation of thrombolysis in myocardial infarction frame count with insulin resistance in patients with slow coronary flow

BackgroundIt has been reported that coronary endothelial dysfunction plays an important pathogenetic role in patients with slow coronary flow (SCF). Insulin resistance is defined as impairment of insulin-stimulated glucose and/or lipid metabolism, while endothelial dysfunction is defined as paradoxical or inadequate endothelial-mediated vasodilation. In this study, we aimed to evaluate insulin resistance in patients with SCF. MethodsThe study population included 25 patients with SCF and 28 healthy controls. Insulin resistance was estimated via homeostasis model assessment insulin resistance index (HOMA-IR). ResultsPatients with SCF had higher high-sensitive C-reactive protein (hs-CRP) and HOMA-IR scores (P<0.05) than controls. Mean thrombolysis in myocardial infarction frame count had significant correlation with hs-CRP, fasting plasma insulin levels and HOMA-IR score (r=0.566, P<0.05; r=0.883, P<0.05; r=0.884, P<0.05, respectively). ConclusionIn patients with SCF, thrombolysis in myocardial infarction frame counts and hs-CRP are correlated with increased insulin resistance and thus, it can be suggested that insulin resistance and inflammation may, in part, have a role in the pathogenesis of SCF.

A comparison of 1-month and 6-month clopidogrel therapy on clinical and angiographic outcome after stent implantation

In this study, we aimed to disclose the net effect of long-term (6-month) clopidogrel treatment as compared to that of short-term (1-month) treatment in the poststenting period. A total of 278 patients with successful stent implantation were involved in the study. After preloading with 300 mg of clopidogrel orally (p.o.) 24 h prior to the procedure, randomly selected patients were given either 75 mg p.o. for 1 month (group A) or 75 mg p.o. for 6 months (group B). The patients were followed up clinically and underwent control angiography at 6 months regardless of their clinical status to delineate the coronary anatomy and assess quantitative computer-assisted (QCA) analysis. In 140 (50.4%) patients (group A), 244 (50.6%) stents were used to treat 237 coronary lesions, and in 138 patients (group B), 238 (49.4%) stents were used to treat 238 coronary lesions. There was no difference between the groups with respect to any of the clinical characteristics, intracoronary thrombus, antiaggregant therapy, the type of lesion, vessel score index, and baseline QCA parameters. In 62 patients binary in-stent restenosis (ISR) was determined with no statistical difference between the groups (group A: 20.7% vs group B: 23.9%, P = not significance). There was also no difference between the two groups at 6 months regarding QCA parameters. Thirty-seven of the 62 patients with restenosis have developed major adverse coronary events such as death, myocardial infarction, and target vessel revascularization (group A: 12.9% vs group B: 13.8%, P = not significant). In patients with chronic coronary syndrome, in the poststenting period, 6-month clopidogrel use as an adjunct to aspirin has shown no benefit over 1 month use with respect to clinical outcome and angiographic outcome, such as restenosis rate, follow-up, minimal luminal diameter, late loss, lost index, and net gain.

Predictive Value of P‐Wave Signal‐Averaged Electrocardiogram for Atrial Fibrillation in Acute Myocardial Infarction

Background: Atrial fibrillation (AF) is a common complication of acute myocardial infarction (AMI) with a reported incidence of 7–18%. Recently, P‐wave signal‐averaged electrocardiogram (P‐SAECG) has been used to assess the risk of paroxysmal AF attacks in some diseases. The aim of this study was to determine prospectively whether patients with AMI at risk for paroxysmal AF would be identified by P‐SAECG and other clinical variables.

The relationship between paraoxonase-1 activity and coronary artery disease in patients with metabolic syndrome.

OBJECTIVES We investigated the correlation of serum paraoxonase-1 (PON-1) activity with coronary artery disease (CAD) in patients with metabolic syndrome (MetS). STUDY DESIGN The study included 21 patients (mean age 55 ± 9 years) with MetS, stable angina pectoris, and angiographically shown CAD, 24 patients (mean age 51 ± 10 years) with MetS and angiographically normal coroner arteries, and 28 healthy controls (mean age 49 ± 12 years). Demographic and clinical characteristics, insulin levels, homeostasis model assessment of insulin resistance index, and PON-1 activity were assessed in all the groups. Severity of CAD was assessed using the Gensini score. RESULTS Paraoxonase-1 activity was significantly lower in patients with MetS compared to the control group (p=0.02). The two MetS groups with and without CAD exhibited similar characteristics in all the parameters including PON-1 activity (p>0.05). Univariate correlation analysis performed in MetS-CAD patients showed a significant negative correlation between the Gensini score and PON-1 activity (r=-0.48, p=0.02). The overall PON-1 activity of all the subjects showed no correlation with the parameters examined. CONCLUSION Decreased PON-1 activity in patients with MetS compared to the control group suggests increased oxidative stress in MetS. Detection of similar PON-1 activity levels in MetS groups with and without CAD suggests that disturbance of oxidative-antioxidative balance occurs before the development of CAD. The negative correlation between the Gensini score and PON-1 activity implies that decreased PON-1 activity may be one of the etiologic causes of atherosclerotic progress in MetS.

Apolipoprotein E polymorphism in diabetic and non-diabetic patients: does it really contribute to atherosclerosis?

Objective — The exact mechanism of the increased cardiovascular morbidity and mortality in type-2 diabetes is still undefined. The aim of our study was to assess the impact of apolipoprotein E (apo E) polymorphism and other factors on atherosclerotic vascular disease in type-2 diabetic patients.We also examined the association between apo E polymorphism and lipid profile in diabetic patients. Methods and results — We assessed the apo E polymorphism in 295 atherosclerotic patients (124 of them had diabetes (according to WHO criteria) and 171 of them had coronary artery narrowing > 50).The detection of apo E polymorphism was made by Real-Time PCR using a Light-Cycler (Roche diagnostics, GmbH, Mannheim, Germany). Serum triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), lipoprotein (a) [Lp(a)], apolipoprotein A (Apo A) and apolipoprotein B (Apo B) levels were determined by biochemical analyser Genotypic distribution of apo E polymorphism did not differ between diabetic and non-diabetic atherosclerotic patients. The distributions of apo E2/2, E2/3, E2/4, E3/3, E3/4 and E4/4 genotypes in diabetic and non-diabetic atherosclerotic patients were 7.3%: 8.2%, 15.3%: 15.8%, 4.0%: 5.3%, 50.8%: 56.7%, 16.9%: 11.1% and 5.6%: 2.9%, respectively. Participants were grouped as apo E2 (E2/2 or E2/3), apo E3 (E3/3), or apo E4 (E4/4 or E4/3). The distributions of apo E2, E3 and E4 alleles were 23.5%, 52.9%, 23.5%, for diabetic patients, and 25.3%, 59.9%, 14.8% for non-diabetic patients, respectively. The apolipoprotein E genotype was not associated with the lipid levels in diabetic patients. Conclusions — Our findings imply that apo E polymorphism is not related to the development of atherosclerosis in patients with type-2 diabetes.