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.

Are maximum P wave duration and P wave dispersion a marker of target organ damage in the hypertensive population?

BACKGROUND: High blood pressure, left ventricular hypertrophy and diastolic dysfunction may cause hemodynamic and morphological changes in the left atrium, consequently instability and heterogeneity in atrial conduction. This is seen as an increase in maximum P wave duration (P(max)) and P wave dispersion (PD) on the electrocardiogram (ECG). P wave dispersion on ECG has been encountered as a risk factor for atrial fibrillation (AF). The aim of this study is to examine whether PD and P(max) can be used as a non-invasive marker of target organ damage (LVH and diastolic dysfunction) in a hypertensive population. MATERIAL AND METHODS: The study registered a total of 120 cases (mean age 46.9 +/- 10.6 years; 58 [48.3%] males and 62 [51.7%] females), of whom 60 were patients diagnosed as essential hypertension (group 1), and 60 were healthy individuals, who constituted the control group (group 2). Systolic and diastolic functions of all cases were evaluated by echocardiography, and maximum P wave duration (P(max)), and PD was calculated. RESULTS: Maximum P wave duration was 91.6 +/- 10.2 ms in group 1, and 64 +/- 10.2 ms in group 2 (p < 0.01), while PD was 56.1 +/- 5.8 ms in group 1, and 30.3 +/- 6.6 ms in group 2 (p < 0.01). Blood pressure, left atrium diameter, DT, IVRT, and E/A ratio, as well as left ventricular mass index increased markedly in group 1. CONCLUSION: High blood pressure, LVH, diastolic dysfunction and increased left atrium diameter and volume shows parallelism in hypertensive cases. These physiopathological changes may cause different and heterogeneous atrial electrical conduction. This led to a marked increase in P(max) and PD in our cases. Thus, the results support the hypothesis that PD can be used as a non-invasive marker of target organ damage (LVH and LV diastolic dysfunction) in the hypertension population.

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.

Effect of diltiazem and metoprolol on left atrial appendix functions in patients with nonvalvular chronic atrial fibrillation.

OBJECTIVES: Thrombo-embolic events are the important cause of mortality and morbidity in patients with chronic atrial fibrillation (CAF). The origin of thromboembolism is often the left atrial appendix (LAA). Flow rate velocity (FRV) inside the LAA is the major determinant of thrombus formation. The aim of our study was to investigate the effects of diltiazem and metoprolol used for ventricular rate control on FRV of the LAA in CAF patients and thus to evaluate the positive or negative effects of these two drugs on thromboembolic events. METHODS: Sixty-four patients were included in the study. All patients were suffering from CAF for more than a year. The patients were allocated to two groups according with agent used for rate control- metoprolol (Group 1; n=31) and diltiazem (Group 2; n=33). Transesophageal echocardiography was applied to all patients and LAA FRV was measured by a pulse wave Doppler in the 1/3 proximal portion of the LAA. The measurements were repeated after applying 5 mg metoprolol to Group 1 and 25 mg diltiazem to Group 2 via venous cannula. RESULTS: In Group 1 after metoprolol LAA flow velocity changed from 0.25 +/- 0.90 m/s to 0.25 +/- 0.10 m/s (p>0.05). In group 2 after diltiazem left atrial appendix FRV decreased from 0.21 +/- 0.9 m/s to 0.19 +/- 0.6 m/s (p>0.05). CONCLUSIONS: In patients with CAF metoprolol used for ventricular rate control had no effect on LAA flow velocity and the observed decrease in LAA flow rate velocity with intravenous diltiazem was insignificant.

Oral mycophenolate mofetil prevents in-stent intimal hyperplasia without edge effect.

Neointimal hyperplasia is in the forefront in in-stent restenosis. Prevention of in-stent restenosis is possible by reducing and inhibiting the hyperplasia of smooth muscle cells. The authors planned this study to test the hypothesis that when administered orally, mycophenolate mofetil (MMF) could inhibit in-stent neointimal hyperplasia. The study included 14 New Zealand rabbits. The rabbits were allocated to 2 different groups: Group 1 included 7 rabbits that were given MMF, 40 mg/kg/day by oral route. Group 2 included 7 rabbits that were not given MMF after the stenting. Sampling materials were taken before and after stenting by incising the artery so as to cover a 5-mm area. The samples taken from the edge of the stent in Group 1 showed focal neointimal cell proliferation, but it was less than that from the control group. Neointimal thickness was 0.048 +/-0.009 mm and neointimal area was 0.0925 +/-0.019 mm(2). Apparent neointimal cell proliferation and thickening of the intimal layer were observed in Group 2. Neointimal thickness at the stent edge was 0.147 +/-0.051 mm and the neointimal area was 0.154 +/-0.023 mm(2). The differences between groups in terms of neointimal thickness and neointimal area were statistically significant (p=0.001 for thickness and p=0.001 for area). In-stent artery samples of Group 1 showed that some subjects had no neointimal cell proliferation, while others had very limited focal intimal thickening. Neointimal thickening was 0.071 +/-0.003 mm and neointimal area was 0.073 +/-0.003 mm(2). In Group 2 apparent, and mostly focal, neointimal cell proliferation and formation of intimal layer were observed in the stent. Neointimal thickening was 0.154 +/-0.069 mm and neointimal area was 0.279 +/-0.059 mm(2). The comparison between groups showed significant differences (p=0.011 for thickness and p=0.001 for area). It was established in the third month that endothelialization was completed in both groups. Oral MMF decreased in-stent intimal hyperplasia without edge effect. It was concluded that for the prevention of in-stent restenosis, studies should be conducted for using systemic immunosuppressive treatments in humans as well.

Excimer laser coronary angioplasty in acute myocardial infarction.

We evaluated the short-term results of percutaneous excimer laser angioplasty in acute myocardial infarction. Of the 18 patients studied, 2 were female and 16 male with a mean age of 56.6 +/- 12.1 years. Thrombolysis in myocardial infarction grades 0, 1, and 2 flow was observed in 10, 5, and 3 cases, respectively, prior to the procedure. The degree of stenosis was 97.9% +/- 5.1%. The lesion was crossed with a laser catheter in all cases, using a mean number of 808 +/- 384 laser pulses. Type C dissection developed in only 1 case (6%). Except for this case, distal flow was grade 3 in all the patients. Following the procedure, ST segment resolution exceeding 70% was achieved in 14 cases (78%) within the first 90 minutes. The success rate of laser ablation was 94% (17 patients). Stent implantation was performed in all the cases. In conclusion, laser angioplasty is an effective and reliable treatment for acute myocardial infarction.

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.

Effect of renal artery stenting on renal function in patients with ischemic nephropathy.

The aim of this study was to evaluate the effects of stenting on blood pressure and renal functions in azotemic patients with proximal/ostial atherosclerotic renal artery stenosis. Thirteen azotemic patients (5 females, 8 males, average age, 62.7 +/- 8.3 years) who had renal artery stenosis were included in the study. Their blood pressure, estimated glomerular filtration rate (EGFR), and creatinine levels were measured at baseline and during follow-up. Stents were implanted successfully in all of the cases. The average stent diameter and stent length were 7.2 +/- 0.5 mm and 17.2 +/- 3.4 mm, respectively. Antihypertensive drug was abandoned in 1 (7.6%) patient, reduced in 10 patients (76.9%), and not changed in 2 (15.3%) patients. Significant improvement was observed in the mean serum creatinine level at the 12th month when compared with baseline (2.56 +/- 0.88; 1.83 +/- 0.62, P < 0.001). EGFR was 18.38 +/- 4.64 before the procedure and 22.67 +/- 3.81 during follow-up (P < 0.0001). According to the GFR criteria, renal function was determined to be worse in 1 (7.6%) patient, stabilized in 2 (15.3%), and improved in 10 (76.9%) patients. One patient died during the follow-up period. Angiographic restenosis was observed in 2 (15.3%) patients. Follow-up major events were observed in 3 (23%) patients. Stenting azotemic patients with renal artery stenosis is a reliable and effective procedure for achieving an improvement in renal function.

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.

Use of excimer laser for thrombus containing lesion.

The presence of thrombus in the lesion before balloon angioplasty increases the complications arising from mechanical intervention. It is known that the use of Gp llb/llla receptor blockers before the intervention enhances the reliability of the procedure. Laser thrombolysis was applied to a patient who underwent coronary angiography due to recurrent chest pain after thirty six hour administration of tirofiban and who was found to have a thrombus so large as to block the distal vessel bed of the right coronary artery. Following the procedure, the entire thrombus was broken down and Grade III distal myocardial perfusion was achieved. This case is important in demonstrating that laser application is a viable alternative in such instances, especially considering that intervention in acute coronary syndromes is on the increase and cardiologists will frequently encounter such cases.

Atorvastatin affects C-reactive protein levels in patients with coronary artery disease.

BACKGROUND: Elevated levels of C-reactive protein (CRP) are considered to be one of the indicators of poor prognosis in coronary artery disease (CAD). The aim of this study was to evaluate anti-inflammatory effects of atorvastatin in patients with CAD by measuring serum CRP levels. METHODS: After measuring the baseline levels of CRP and lipid fractions, the patients were divided into two groups. In Group A (n = 46), atorvastatin (20 mg/day) was administered in addition to classic antianginal treatment (beta-blocker, nitrate and aspirin). In Group B (n = 32), the usual antianginal treatment was continued. Following 4 weeks of treatment the same measurements were repeated. RESULTS: In Group A, CRP decreased from 20.3 mg/dl (95% CI, 9-31.8) to 10.8 mg/dl (95% CI, 2.7-18.9) (p < 0.001). In Group B, CRP decreased from 17 mg/dl (95% CI, 13.1-21) to 12.8 mg/dl (95% CI, 9.7-15.9) (p < 0.01). The decrease in group A was more than in group B (p = 0.003). CONCLUSIONS: In patients with CAD, atorvastatin exerted an anti-inflammatory effect represented by decreasing CRP levels. This effect was independent of the change in low density lipoprotein cholesterol (LDL-C) or high density lipoprotein cholesterol (HDL-C) levels.

[Stenting of renal artery with or without predilatation in hypertensive patients with renal artery stenosis: results of the nine-months follow-up]. / Renal arter darligi saptanan hipertansif hastalarda renal artere stent uygulamasi: dokuz aylik takip sonuçlari.

OBJECTIVE: We evaluated the effects of stenting on blood pressure and renal functions in hypertensive patients with proximal/ostial atherosclerotic renal artery stenosis. METHODS: Twenty-six hypertensive patients (9 female, 17 male, mean age 59.0+/-7.4 years) who had renal artery stenosis were included into this study. Their blood pressure, urea and creatinine levels were measured at 24 hours, 3 months and 9 months after procedure. RESULTS: Stents were implanted successfully in all cases. Implanting of stent was done with predilatation in 16 (5%) cases and without predilatation (direct stenting) in 10 (49%) cases. Mean stent diameter and stent length were 7.11+/-0.3 mm and 15.0+/-2.2mm respectively. The antihypertensive drug therapy was stopped in 6 (23%) patients, decreased in 15 patients (58%) and did not change in 5 (19%) patients. No significant changes were observed in urea and creatinine levels. However, creatinine levels were lower after procedure in direct stenting patients than in patients in whom predilatation was applied (0.78+/-0.3 mm; 1.32+/-0.6, p=0.003). This difference disappeared on the 3rd month of follow-up. One patient died during follow-up period. Control angiography was performed in 23 patients. Angiographic restenosis was found in 1 (4.3%) patient. Major events during follow-up period occurred in 2 (8%) patients. CONCLUSION: Stenting in hypertensive patients with renal artery stenosis is reliable and effective procedure. Selection the stenting procedure with or without predilatation depends on the clinical status of patient and the choice of the interventional team.

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.