Prevalence and Characteristics of Coronary Artery Anomalies Using Invasive Coronary Angiography in 6237 Consecutive Patients in a Single Center in Turkey.

BACKGROUND: Coronary artery anomalies (CAAs) include clinically and anatomically diverse types of congenital heart defects occurring in a complicated spectrum. The aim of the present study is to describe congenital anomalies of coronary arteries (CAs) and their variations, and also identify the prevalence of these anomalies in our center. METHODS: The study included a total of 6237 consecutive patients. Cine-angiographies and digital data of all patients undergoing coronary angiography (CAG) were reviewed by at least 2 independent and experienced observers. The Basic Anatomic Classification method was used to classify patients with CAAs. RESULTS: Of a total of 6237 patients, 2,313 were females (37.1%) and 3924 (62.9 %) were males. CAAs were detected in 247 out of 6237 patients (3.9%, 95% CI: 3.4-4.4). Of these patients, 48 (19.4%, 95% CI: 14.4-24.2) had absent left main coronary artery (LMCA), 21 (8.5%, 95% CI: 5-11.9) had anomalous origin from the appropriate sinus, 23 (9.3%, 95% CI: 5.7-12.9) had anomalous origin from structures other than appropriate sinus, 31 (12.6%, 95% CI: 8.5-16.6 ) had anomalous origin from the opposite sinus, 101 (40.9%, 95% CI: 34.8-46.9) had myocardial bridge, and 23 (9.3%, 95% CI: 5.7-12.9) had a coronary artery fistula. CONCLUSION: Our study results suggested that the total rate of coronary anomaly was found much higher than those reported in various invasive angiographic studies.

[The relation of intima-media thickness with endothelial function and left ventricular mass index]. / Brakiyal arter intima-media kalinliginin endotel fonksiyonu ve sol ventrikül kütle indeksi ile iliskisi.

OBJECTIVE: We aimed to investigate the relation of brachial artery intima-media thickness (IMT) with endothelial function and left ventricular mass (LVM). METHODS: Fifty-four stage I-II hypertensive patients according to JNC VII who were not taking any medication and 27 age and sex-matched healthy controls were included to this cross-sectional observational study. IMT was measured by the same radiologist who was unaware of the patient's clinical status by using high resolution ultrasound machine. Endothelial function was evaluated by flow mediated dilation (endothelium-dependent vasodilatation, FMD). LVM was calculated by using Devereux method. LVM index (LVMI) was obtained by dividing LVM to body surface area. Mann-Whitney U test was used to compare continuous variables, qualitative variables were compared by Chi-square test and the relations of parameters were evaluated by multiple linear regression analysis. RESULTS: Both groups (hypertensive and control) were similar with respect to age, sex, left ventricular ejection fraction. IMT was significantly higher in hypertensive group (0.43+/-0.09 vs 0.33+/-0.06 mm; p<0.001). FMD values were also significantly different between hypertensive and control groups (4+/-4% vs 13+/-12%; p<0.001). LVMI was significantly different between hypertensive and control groups LVMI (124 +/- 5 vs 99+/-6 gr/m2, p=0.002). The correlation between IMT and FMD (r=0.260; p=0.026) and IMT and LVMI (r =0.348; p=0.004) were statistically significant. A correlation was found between IMT and LVMI independently of other variables (beta=105; p=0.004) when LVMI was accepted as dependent variable in multivariate linear regression analysis (R2=0.570, p<0.001). According to this finding, the 105 units increase in LVMI occurs when IMT increases by 1 mm. CONCLUSION: Brachial artery IMT is related to endothelial function and LVM. According to these data, any negative changes of the IMT may reflect the similar negative changes in other parameters.

A new noninvasive method in evaluating the endothelial function: the measurement of the resistive index after reactive hyperemia of the brachial artery.

OBJECTIVE: The objective of our study was to investigate whether the measurement of the resistive index (RI) after reactive hyperemia is a relevant method for the evaluation of the endothelial function. MATERIALS AND METHODS: 54 hypertensive patients and 27 controls were prospectively enrolled for the study. In addition to the flow-mediated dilation (FMD), the RI was also measured during the same procedure. RI is a vascular resistance parameter that is most commonly used to minimize the intra- and interobserver variability because of its reliability among repeated measurements. The percent change of the RI after reactive hyperemia (HRI) in comparison to the baseline RI was defined as the flow-mediated RI (FMRI). (FMRI = 100 ×[HRI - baseline RI/baseline RI]). RESULTS: The groups were comparable in terms of age, sex, and left ventricular ejection fraction. Differences were present in the systolic arterial pressure (mmHg; 161 ± 15 vs. 114 ± 7, P = 0.000), diastolic arterial pressure (mmHg; 96 ± 7 vs. 72 ± 7, P = 0.000) and left ventricular mass index (g/m(2;) 124 ± 5 vs. 99 ± 6, P = 0.002). As expected, the FMD differed significantly between hypertensive and control groups (4 ± 4% vs. 13 ± 12%, respectively; P = 0.000). There was also a significant difference in the FMRI values between the groups (-21 ± 10; -30 ± 14, P = 0.002). FMD and FMRI values were negatively correlated (P < 0.05). CONCLUSION: For the noninvasive evaluation of the endothelial function, FMRI value measured as RI value after reactive hyperemia can be a good alternative to the FMD measured as vascular diameter after reactive hyperemia.

Nebivolol and quinapril reduce p-wave duration and dispersion in hypertensive patients.

We aimed to investigate the effects of nebivolol and quinapril treatments on P-wave duration and dispersion in hypertensive patients. Hypertensive patients who were in sinus rhythm were assigned to the two treatment groups and received either 20 mg quinapril/day or 5 mg nebivolol/day. P-Wave dispersion (PWD) was measured at baseline and after four weeks of treatment and defined as the difference between the maximum (Pmax) and the minimum (Pmin) P-wave duration. The study group consisted of 54 patients (Mean age: 53 +/- 9 years, 46% women) with 27 patients in each group. At 4-week follow up both treatment groups showed a significant reduction (p< 0.001) in systolic (SBP) and diastolic blood pressure (DBP). Heart rate (HR) reduction was significant in patients receiving nebivolol (P=0.001). Both groups showed a similar (P=0.413 for PWD, p=0.651 for Pmax) but significant reduction in PWD (nebivolol: -16+/- 14, P< 0.0001 and quinapril: -13+/- 11, P< 0.0001) and Pmax (nebivolol: -10+/- 11, P=0.001 and quinapril: -9+/- 11, P=0.001). A 2 (Time) x 2 (Group) mixed-model repeated-measures analysis of variance revealed that the main effect of Time was significant for Pmax (P=0.002) and PWD (P=0.008) after controlling for changes in SBP, DBP and HR. However, the main effect of Group and Time x Group interaction was not significant for both variables (All p values > 0.05). In conclusion, short-term treatment with nebivolol and quinapril produces a similar but significant reduction in Pmax and PWD in hypertensive patients. This effect is independent of blood pressure and heart rate changes.

Efficacy of clopidrogel on reperfusion and high-sensitivity C-reactive protein in patients with acute myocardial infarction.

We investigated the effects of clopidogrel on reperfusion and inflammatory process in STEMI. A total of 175 STEMI patients with similar clinical characteristics were included to this study. One was the standard pharmacological reperfusion therapy group (group 1, n : 90), who received 300 mg aspirin, 70 U/kg bolus, and 12 U/kg/hr continuous infusion of unfractioned heparin and accelerated t-PA. Clopidogrel 450 mg loading and 75 mg/d thereafter was added to standard reperfusion therapy in the other group (group 2, n : 85). The ST-segment resolution, CK-MB, and high-sensitive CRP (hs-CRP) parameters were measured. Complete ST resolution was observed in 32 patients (36.8%) in group 1 and 53 patients (63.8%) in group 2 (P < .001). Also in the first 24 hours, the CK-MB levels of patients in group 1 were significantly higher than those of group 2 (P = .001). The hs-CRP values were greater in group 1 than group 2 at 48th hour (group 1: 9.4 +/- 0.1 mg/L, group 2: 3.7 +/- 1.4 mg/L; P = .000). We concluded that adding clopidogrel to standard treatment in STEMI patients provided early reperfusion and suppression of inflammatory response.

Obestatin is present in saliva: alterations in obestatin and ghrelin levels of saliva and serum in ischemic heart disease.

Ghrelin and obestatin are a single gene products and are a multiple functional peptides that regulates energy homeostasis, and food intake. In the present work, we studied the secretion of ghrelin and its co-secreted peptide obestatin in 44 patients with ischemic heart disease with that of 27 healthy matched controls. Here we first conducted using an immunohistochemistry assay to screen whether human salivary glands have any obestatin immunoreactivity. Then, serum and saliva obestatin and acylated ghrelin levels were determined by using Radioimmunoassay. Our immunohistochemical analysis demonstrated that obestatin was localized in the striated and excretory duct of human salivary gland. We also report for the first time that obestatin, like ghrelin, is present in human salivary gland and saliva. No evidence of the role of obestatin or ghrelin saliva levels in the context of ischemic heart disease was found. Salivary ghrelin and obestatin levels are correlated in controls with the blood levels. Determination of salivary values could represent a non-invasive alternative to serum ones that can be useful in clinical practice.

The 677 C/T MTHFR polymorphism is associated with essential hypertension, coronary artery disease, and higher homocysteine levels.

BACKGROUND: Essential hypertension (EH) and cardiovascular disease are common, multifactorial disorders likely to be influenced by multiple genes of modest effect. The C677T methylenetetrahydrofolate reductase (MTHFR) gene polymorphism is related to MTHFR enzyme activity and to plasma homocysteine (Hcy) concentration. This study was designed to investigate an association of this polymorphism with coronary artery disease (CAD), EH, and healthy subjects. METHODS: In this study, we measured serum folate, serum vitamin B12, and plasma homocysteine and determined the MTHFR C677T genotype of 78 patients with essential hypertension, 100 patients with coronary artery disease, and 100 healthy subjects. MTHFR genotypes were assessed by real-time polymerase chain reaction. RESULTS: CC, CT, and TT genotype frequencies were 52, 44.0, and 4.0% in patients with CAD, respectively. In patients with essential hypertension, the CC, CT, and TT genotype frequencies were 46.2, 41.0, and 12.8%, respectively. In control subjects, the CC, CT, and TT genotype frequencies were 72.0, 26.0, and 2.0%, respectively. The C allele was significantly more frequent in controls compared with patients with EH (p<0.05), and CC genotypes were more frequent in controls compared to patients with EH and CAD. Homocysteine level was higher in TT genotypes in CAD patients compared with CC and CT genotypes (p<0.01). MTHFR gene polymorphism is an independent risk factor for EH but not for CAD. CONCLUSIONS: The TT genotype of the 677C/T MTHFR polymorphism is associated with EH and CAD. In addition, TT genotypes had higher plasma Hcy levels in CAD patients compared with CC and CT genotypes. MTHFR gene polymorphism is an independent risk factor for EH but not for CAD.

B-type natriuretic peptide level in the diagnosis of asymptomatic diastolic dysfunction.

OBJECTIVE: Brain natriuretic peptide (BNP) reflects the left ventricular pressure and volume overload. It is known that it increases in systolic dysfunction proportionally with left ventricular pressure increase. The BNP levels are well correlated with NYHA classification and prognosis. Our aim was to evaluate the predictive value of BNP in patients with diastolic dysfunction but normal systolic dysfunction demonstrated by echocardiography. METHODS: Fifty patients (mean age: 48.5+/-6.75 years; 29 males, 21 females) were included in this cross-sectional, case-controlled study. Systolic dysfunction was the exclusion criterion. The following parameters were used to evaluate diastolic function: isovolumetric relaxation time, transmitral early to late filling flow velocities (E/A) ratio, deceleration time E, pulmonary vein Doppler findings and color mitral flow propagation velocity. Diastolic dysfunction was determined in 30 hypertensive patients (Group 1), whereas 20 patients who had normal diastolic flow patterns on echocardiography (Group 2). Blood samples were taken for serum BNP level measurements. RESULTS: The BNP levels were 12.0+/-4.97 pg/ml in individuals with normal filling pattern and 66.17+/-17.56 pg/ml in individuals with abnormal filling patterns (p<0.001). The accuracy of BNP in detection of diastolic dysfunction was assessed with receiver-operating characteristic (ROC) analysis. The area under the ROC curve for BNP test accuracy in detection any abnormal diastolic dysfunction was 0.969 (95% CI, 0.909 to 1.029; p<0.001). A BNP value of 37.0 pg/ml had sensitivity of 80%, specificity of 100%, a positive predictive value of 100%, a negative predictive value of 23% and accuracy of 88% in identifying asymptomatic prolonged relaxation pattern. We found a strong correlation between left ventricular mass index and plasma BNP levels (r=0.62, p<0.05). CONCLUSION: Estimation of BNP values could be accepted as a fast and reliable blood test in the diagnosis of asymptomatic diastolic dysfunction.

The level of hs-CRP in coronary artery ectasia and its response to statin and angiotensin-converting enzyme inhibitor treatment.

BACKGROUND/AIM: Coronary artery ectasia (CAE) was thought of as a variant of atherosclerosis. C-reactive protein (CRP) which is among the most sensitive markers of systemic inflammation, and elevation of systemic and local levels of this inflammatory marker which has been associated with an increased risk for cardiovascular disease in the obstructive coronary artery disease (O-CAD) are well known, but little was known in CAE. The anti-inflammatory effects of statins and the effect of angiotensin-converting enzyme (ACE) inhibitors on endothelial dysfunction are well established in atherosclerosis. The aim of the present study was to investigate CRP level and its response to statin and ACE inhibitor treatment in CAE. MATERIALS AND METHOD: We measured serum hs-CRP level in 40 CAE (26 males, mean age: 56.32 +/- 9 years) and 41 O-CAD (34 males, mean age: 57.19 +/- 10 years) patients referred for elective coronary angiography at baseline and after 3-month statin and ACE inhibitor treatment. RESULTS: Plasma hs-CRP levels were significantly higher in CAE group than O-CAD group at baseline (2.68 +/- 66 mg/L versus 1, 64 +/- 64, resp., P < .0001). Plasma hs-CRP levels significantly decreased from baseline 3 months later in the CE (from 2.68 +/- 0.66 mg/L to 1.2 +/- 0.53 mg/L, P < .0001) as well as in the O-CAD group (from 1.64 +/- 0.64 mg/L to 1.01 +/- 0.56 mg/L, P < .001). CONCLUSION: We think that hs-CRP measurement may be a good prognostic value in CAE patients as in stenotic ones. Further placebo-controlled studies are needed to evaluate the clinical significance of this decrease in hs-CRP.

Abnormal asymmetric dimethylarginine/nitric oxide balance in patients with documented coronary artery disease: relation to renal function and homocysteine.

BACKGROUND: As an endogenous inhibitor of nitric oxide production, asymmetric dimethylarginine (ADMA) is reported to be associated with coronary artery disease (CAD). METHODS: We measured plasma levels of ADMA, nitrate + nitrite (NOx), total homocysteine (tHCY), and renal function in 106 people with angiographic evidence of coronary artery disease (CAD), including 46 with single vessel disease and 60 with double/triple vessel disease, and in 70 age-matched individuals without any angiography evidence of CAD. Also the levels of these parameters were evaluated according to their history of MI. Plasma tHcy and ADMA were measured by HPLC and the levels of NOx using the Griess reaction. RESULTS: Levels of ADMA, ACE and tHcy levels were significantly higher and NO level was significantly lower in CAD patients compared with controls but there were no significant differences among patients with or without history of MI and between patients with single compared to those with double/triple vessel disease. Additionally a negative correlation was found between ADMA-NOx (r = -0.396, p = 0.001) and between tHcy-NOx (r = -0.262, p = 0.027). In the entire study group, ADMA level was significantly higher in patients with creatinine clearance (CrCl) < 91 mL/min than in patients with CrCl > or = 91 mL/min (0.60 +/- 0.23 micromoles/L versus 0.49 +/- 0.25 micromoles/L, p = 0.05). CONCLUSIONS: We suggest that there is an abnormal plasma ADMA-to-NO balance in patients with documented CAD and that this may be due at least in part to an associated reduction in renal function.

The relationship between ACE insertion/deletion polymorphism and coronary artery disease with or without myocardial infarction.

OBJECTIVES: Presence of the D allele or homozygosity for the deletion (D) allele of the angiotensicen-converting enzyme (ACE) insertion/deletion (I/D) polymorphism has been discussed as potent risk factor for coronary artery disease (CAD) and myocardial infarction (MI). The D allele is associated with higher levels of circulating ACE and therefore may predispose one to cardiovascular damage. DESIGN AND METHODS: The study presented here was performed to investigate the association between the ACE genotype and ACE levels. The study group was comprised of 118 angiographically verified CAD patients. 65 patients were MI (+) and 53 patients were MI (-) in this group. A total of 70 healthy individuals were taken as controls. Genomic DNA of 188 subjects was extracted from whole blood. The polymerase chain reaction was used for ACE genotyping, and ACE levels were measured by ELISA. RESULTS: The D allele was found to be significantly more frequent in patients with MI (+) compared with controls (P = 0.024). ACE levels were significantly higher in both MI (-) and MI (+) groups with CAD patients than in controls (P < 0.005). Plasma ACE level was higher in all three groups in the DD genotype compared to II genotype. In groups I and III, this was statistically significant (P < 0.0001, P < 0.01). CONCLUSIONS: It was shown that the I/D polymorphism in the gene for ACE is a genetic risk factor for CAD patients who have a history of MI. ACE insertion/deletion gene polymorphism is also associated with plasma ACE levels in CAD patients with a history of MI.

Effects of tirofiban on acute systemic inflammatory response in elective percutaneous coronary interventions.

OBJECTIVE: In this study the effect of a specific glycoprotein IIb/IIIa inhibitor, tirofiban [which also has antiplatelet activity on acute systemic inflammatory responses (IR) during elective percutaneous coronary intervention (PCI)] was evaluated. PATIENTS AND METHODS: Patients with stable angina pectoris and similar baseline characteristics who angiographically had a single lesion in their coronary arteries with a PCI performed on that lesion were enrolled in the study. One group of patients (control group, n = 52) received 0.9% NaCl (15 mL/h for 24 h) and the other group (tirofiban group, n = 55) had tirofiban (10 microg/kg bolus infusion in 3 min and 0.15 microg/kg/min for 24 h) in addition to stenting without pre-dilatation. The effect of interventional procedure on levels of cardiac troponin T (cTnT) and several parameters of acute IR (leukocytes, fibrinogen, C-reactive protein, interleukin-1, interleukin-6, interleukin-8 and tumor necrotizing factor-alpha) was assessed on blood samples obtained from all patients before PCI and at pre-specified time points after PCI. RESULTS: During the follow-up after PCI, the number of patients becoming cTnT-positive (> 0.1 ng/mL) was greater in the control group [12 (23%) patients vs. 3 (5%) patients, p = 0.01]. However, both groups had changes (generally observed as elevations) in their levels of all inflammatory parameters during the study and C-reactive protein, interleukin-6 and tumor necrotizing factor-alpha levels were elevated significantly. Yet, no significant difference occurred between groups due to these changes in any phase of the study (p > 0.05). CONCLUSIONS: Based on the findings of this study, it was concluded that although tirofiban limits development of myocardial necrosis during elective PCI, it does not directly affect the acute systemic inflammatory responses.

The effect of long-term clopidogrel use on neointimal formation after percutaneous coronary intervention.

OBJECTIVE: The purpose of this study was to evaluate the long term effect of clopidogrel-based antiplatelet therapy on neointimal formation. METHODS: This study comprised 78 patients with typical stable angina pectoris or documented myocardial ischaemia, and with only one angiographic lesion in one native coronary artery undergoing successful stent implantation without predilatation with C-reactive protein levels < or =5 mg/l at 72 h after the procedure. All patients received dual antiplatelet therapy with 75 mg/day clopidogrel and 300 mg/day aspirin for four weeks. Clopidogrel was switched to isochronous placebo in half of the patients (n=39) at the end of the fourth week. This allocation was maintained for 20 weeks, and at week 24 of the study, coronary angiography and intravascular ultrasound imaging were performed again in all cases in order to evaluate the changes that had occurred in the in-stent neointimal formation; rates of restenosis were also recorded RESULTS: At the end of the follow-up period, angiographic stenosis diameter and restenosis rates were smaller in the clopidogrel group than in the placebo group (23.3% versus 35.6%, p=0.05 and 5.12% versus 10.25%; p=0.03 respectively); the intravascular ultrasonographic neointimal cross sectional area was also smaller in the clopidogrel group (3.6 +/- 2.7 mm(2) versus 5.2 +/- 2.5 mm(2), p=0.03). CONCLUSIONS: Long-term clopidogrel administration significantly reduced neointimal formation at the stent site as well as reducing major clinical events in patients who did not develop high-risk systemic inflammatory response after percutaneous coronary intervention.

Effects of spironolactone and metoprolol on QT dispersion in heart failure.

The effects of spironolactone or metoprolol added to a conventional treatment protocol on QT dispersion, which is accepted as a sudden cardiac death predictor, were evaluated in heart failure patients.? A total of 105 New York Heart Association class III patients were included in this study. The conventional treatment protocol was standardized by giving ramipril, furosemide, and digoxin to all patients for 3 weeks at the same doses. At the end of this period, the patients were divided into three groups. Conventional treatment was continued in group 1, 25 mg spironolactone was added in group 2, and 12.5 mg metoprolol was added in group 3. Patients were followed for 12 weeks and clinical and laboratory tests were conducted at 3 week intervals. No significant change in corrected QT dispersion was observed in group 1 at the end of 12 weeks (corrected QT dispersion: 80 +/- 2 msc to 79 +/- 2 msc, P: 0.22). However, corrected QT dispersion in group 2 was reduced by 32.5% (83 +/- 2 msc to 56 +/- 1 msc; P: 0.01). A 32.9% reduction in corrected QT dispersion (79 +/- 2 msc to 53 +/- 2 msc; P: 0.01) was observed in group 3. In conclusion, the addition of spironolactone or metoprolol to a conventional treatment in heart failure patients resulted in improved clinical conditions and the significant decrease in sudden death predictors corrected QT dispersion. The effects of spironolactone and metoprolol on corrected QT dispersion were similar.

A single center experience with the newly designed R Stent in small coronary vessels.

BACKGROUND: Over the past 10 years stents have been used more frequently for the treatment of de novo coronary artery stenosis. Initally these devices were used primarily in coronary arteries with diameters ranging from 3.0 to 4.0 mm. Traditionally, coronary arteries less than 3.0 mm in diameter were treated with only balloon angioplasty, due to the unavailablity of flexible, low profile, small diameter stents. In the past three years, many stents have been designed to be implanted in small coronary arteries. OBJECTIVE: The objective of this study was to evaluate the safety and feasiblity of the R Stent in patients with coronary lesions located in coronary arteries with a reference diameter 2.5-3.0 mm. METHODS AND RESULTS: Between November 1998 and September 1999, 32 patients with stable (37%) and unstable (63%) angina treated with the R Stent were included in this study. The treated lesions were in the right coronary artery (RCA) (n = 13), left cirumflex coronary artery (LCX) (n = 10), and left anterior descending coronary artery (LAD) (n = 9). Of these lesions thirteen were anatomically complex. Stent deployment was successful in 97% with one crossing failure in a patient with a vessel tortuosity of greater than 75 degrees of the circumflex artery. No post-procedual major adverse cardiac and cerebrovascular event (MACCE) occurred within 30 days of stent implantation. After the procedure, patients were scheduled for a two-week telephone follow-up and a one-month clinical evaluation. At 30 days, only one patient (3%) experienced the recurrence of angina Canadian cardiovascular society classification ((CCS) Class 2). All other patients were event and angina free. CONCLUSION: This first clinical experience in patients with small vessel disease shows that the use of the R stent is safe and feasible with low rates of acute stent thrombosis.