The effect of anti-tumor necrosis factor (TNF)-alpha therapy with etanercept on endothelial functions in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the effects of tumor necrosis factor (TNF)- alpha antagonism with etanercept (ENC) on endothelial functions in patients with active rheumatoid arthritis (RA). METHODS: A total of 21 patients with RA were enrolled in this prospective study. Eleven of them (8 women, 3 men mean age 47.0+/-10.1 years) with high disease activity despite the conventional treatment were assigned to Group 1 and were given ENC treatment twice a week (25 mg SC injection) for 12 weeks. Ten patients with RA (8 women, 2 men mean age 55.0+/-6.4 years) under conventional methotrexate and prednisone therapy were assigned as Control group (Group 2). Endothelium-dependent and -independent vasodilator responses of the brachial artery were assessed by high-resolution ultrasound. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were also measured at baseline and at the post treatment period. Mann-Whitney U and Wilcoxon tests were used to compare the data and correlation analysis was performed using Pearson correlation test. RESULTS: Endothelium-dependent vasodilatation improved from 5.2+/-0.8% to 7.9+/-1.3% (p=0.04) in ENC group, while no significant change was observed in the control group (from 6.6+/-1.1% to 7.0+/-1.8% p=0.67). No significant changes were found in endothelium-independent vasodilatation and baseline brachial artery diameters in both groups. A significant reduction in ESR and CRP were observed in patients receiving ENC (from 16.2+/-6.8 to 9.2+/-5.1 mm/h, p=0.003 and from 14.68+/-3.4 to 9.25+/-3.7 mg/L, p=0.003, respectively). CONCLUSION: Treatment with ENC for 12 weeks significantly improved endothelial function in patients with active RA compared to those under conventional therapy. The findings of the present study support the hypothesis that the use of TNF-alpha blockers in patients with active RA may reduce the high incidence of cardiovascular complications.

Effects of Angiotensin-converting enzyme inhibition and statin treatment on inflammatory markers and endothelial functions in patients with longterm rheumatoid arthritis.

OBJECTIVE: To investigate the effects of angiotensin-converting enzyme (ACE) inhibitors and statins (hydroxy-methyl-glutaryl-CoA reductase inhibitors) on inflammatory markers and endothelial functions in patients with rheumatoid arthritis (RA). METHODS: A total of 45 patients with longterm RA were randomized into 3 groups to receive 8 weeks of treatment with placebo (n = 15), simvastatin (20 mg/day, n = 15), or quinapril (10 mg/day, n = 15) as an adjunct to existing antirheumatic drug treatment. Factors with a role in the development of endothelial dysfunction, such as C-reactive protein (CRP), fibrinogen, nitric oxide (NO), and serum cytokine concentrations including interleukin 1beta (IL-1beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha) were measured at baseline and in the posttreatment period. Brachial artery vasodilator responses were assessed by high resolution ultrasound to evaluate endothelial functions. RESULTS: Simvastatin treatment significantly decreased serum CRP and TNF-a [from 14 +/- 6 to 7 +/- 3 mg/l (p = 0.025) and 30 +/- 5 to 16 +/- 4 pg/ml (p = 0.012), respectively], while quinapril had no significant changes in these 2 measures. IL-1beta and IL-6 showed insignificant changes in patients in the 2 drug groups. Endothelium-dependent vasodilatation was improved significantly in the simvastatin group [from 5.3 +/- 1.1% to 8.9 +/- 1.4% (p = 0.025)], while there was no difference in endothelium-independent vasodilatation [9.0 +/- 1.8% to 11.2 +/- 2.5% (p = 0.17)]. The quinapril group showed no significant changes in both types of vasodilation although there was a tendency to an increase in endothelium-dependent vasodilatation [from 6.1 +/- 0.8% to 7.8 +/- 0.7% (p = 0.06)]. Treatment with the 2 drugs had no significant effects on resting arterial diameter. CONCLUSION: We show that simvastatin 20 mg daily improves endothelial function in patients with RA. Its beneficial effect may be attributed to lowering CRP and TNF-alpha concentrations. ACE inhibition with daily 10 mg quinapril was found to have no significant effects on inflammatory markers and endothelial vasodilator response.

Endothelial dysfunction in patients with primary Sjögren's syndrome.

The aim of this study was to determine the endothelial function in patients with primary Sjögren's syndrome (SS). We also aimed to determine whether endothelial (dys)function correlates with extraglandular manifestations, specific autoantibodies and the severity of salivary gland involvement of SS. Endothelium-dependent vasodilation and endothelium-independent vasodilation of the brachial artery were assessed by a high-resolution ultrasound on 25 patients with primary SS and on 29 healthy controls. Patients with primary SS had significantly less mean endothelium-dependent vasodilation than did controls (3.0 +/- 0.4% vs 4.2 +/- 0.3%; p = 0.012). Endothelium-independent vasodilation induced by sublingual glycerol trinitrate was not different between the two groups (12.9 +/- 1.4% vs 14.1 +/- 1.2%; p = 0.86). We concluded that endothelium-dependent vasodilation was impaired in primary SS patients, in particular those presenting with Raynaud's phenomenon, when compared with the healthy controls and this impairment was not associated with the presence of RF, ANA, anti-Ro/SS-A, anti-La/SS-B and with the other extraglandular manifestations of the disease.

[The effects of clarithromycin treatment on cardiac events in acute coronary syndrome patients]. / Akut Koroner Sendromlu Hastalarda Klaritromisin Tedavisinin Kardiyak Olaylar Uzerine Etkisi.

OBJECTIVE: The assessment of short duration early clarithromycin treatment on major cardiac events in acute coronary syndrome patients. METHODS: One hundred and thirteen patients with acute coronary syndrome had been enrolled in the study in a prospective manner. Fifty-seven of 113 patients received peroral clarithromycin 1g/day for 14 days in addition to standard therapy. The remaining 56 patients were considered as control group. The treatment and control groups had similar major cardiac risk factors such as diabetes, hypertension, dyslipidemia and smoking habits. The occurrence of unstable angina pectoris, non-ST elevation myocardial infarction and ST elevation myocardial infarction was comparable in both groups. The use of thrombolytic therapy and glycoprotein IIb/IIIa receptor blockers administration was also similar in both groups. The patients were followed for major cardiac events for 6 months. RESULTS: During the follow-up, no difference was observed between groups in the occurrence of unstable angina pectoris, myocardial infarction, the need for revascularization with percutaneous coronary intervention or cardiac surgery and cardiac death. We observed a reduction of myocardial infarction and cardiac death occurrence and an increase in the necessity of percutaneous interventions in the treatment group even though this difference did not reach statistical significance. CONCLUSION: No benefit of short duration early clarithromycin therapy was observed in the occurrence of major cardiac events in acute coronary syndromes. Studies with longer treatment and follow-up period using different antibiotics are necessary to elucidate the possible effect of antibiotics on major cardiac events in patients with acute coronary syndrome.

The effect of simvastatin on serum cytokine levels and bone metabolism in postmenopausal subjects: negative correlation between TNF-alpha and anabolic bone parameters.

In this prospective study, we aimed to evaluate the effect of simvastatin on bone metabolism and the correlation between changes in bone turnover parameters and serum cytokine levels. For this purpose, 38 postmenopausal subjects with hypercholesterolemia (>240 mg/dl), not on osteoporosis treatment, were studied. Simvastatin was started at a dose of 20 mg daily and continued for 3 months. Six patients were excluded from the study during the follow-up period. Pre- and post-treatment samples were analyzed for bone alkaline phosphatase (BAP) and osteocalcin (OCL), as markers of bone formation; for carboxyterminal telopeptide of collagen I (CTX), as a marker of bone resorption; and for interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) cytokine levels. Total cholesterol level was decreased from 262.1 +/- 30.9 to 210.2 +/- 35.6 mg/dl after simvastatin treatment (P < 0.0001). While no significant change was observed in serum CTX level, BAP and OCL levels were significantly increased (from 120.8 +/- 56.6 to 149.5 +/- 57.6 IU/l [P = 0.008], and from 20.8 +/- 12.6 to 34.7 +/- 18.4 microg/l [P = 0.015], respectively). In the analysis of cytokines, while no significant change was observed in IL-6 levels, the TNF-alpha level was found to be significantly decreased after simvastatin treatment (from 77.9 +/- 31.6 pg/ml to 23.5 +/- 12.6 pg/ml [P = 0.021]). Individual changes in TNF-alpha levels showed a moderate negative correlation with the individual changes in BAP and OCL levels (r = -0.550 [P = 0.001], and r = -0.497 [P = 0.004], respectively). In conclusion; 20-mg daily simvastatin treatment for 3 months significantly increased BAP and OCL levels (markers of bone formation) in hypercholesterolemic postmenopausal subjects, without affecting bone resorption. These findings support the idea that simvastatin has an anabolic effect on bone formation. Additionally, the presence of a negative correlation between TNF-alpha levels and the anabolic bone parameters suggests that a cytokine-lowering effect of simvastatin may also be involved in the remodeling process and could exert some additive beneficial effect on bone metabolism.

Differential effect of aspirin on platelet aggregation in patients with coronary artery disease in relation with associated risk factors.

Platelets play a key role in the pathogenesis of atherosclerosis and acute coronary syndromes and antiplatelet therapy offers a clinical benefit. Although aspirin is the most widely used agent, there are several conditions in which aspirin may fail to provide a full antithrombotic benefit. Furthermore, data concerning the relationship between platelet function, aspirin, and the associated risk factors are limited. In the present study. ADP and collagen-induced platelet aggregation of 200 consecutive patients with suspected coronary artery disease (CAD) who underwent coronary angiography were evaluated. The patients were classified into three groups according to the number of stenotic vessels. One hundred and eight patients were using 300 mg/day of aspirin. The associated cardiovascular risk factors were also considered. The collagen-induced platelet aggregation of smokers was significantly higher than non-smokers (P < 0.05). Although platelet aggregation was higher in diabetic and hypertensive patients, the difference was not statistically significant. No significant correlation was found between platelet aggregation and other risk factors. The collagen-induced platelet aggregation of the subjects with non-stenotic vessels was reduced by aspirin (P < 0.05). Aspirin did not sufficiently inhibit ADP and collagen-induced aggregation in patients with CAD. This finding supports the idea that the nonplatelet-mediated effects of aspirin could be more important than its antiplatelet effect in clinical use and the use of new potent antiplatelet drugs may complete its antiplatelet effect.

Left ventricular aneurysm formation after anterior myocardial infarction: clinical and angiographic determinants in 809 patients.

BACKGROUND: Previous studies have reported controversial results regarding the clinical and angiographic factors involved in the left ventricular aneurysm (LVA) formation after myocardial infarction (MI). OBJECTIVE: This study was performed to determine the clinical and angiographic factors that are priori predictors of LVA following anterior myocardial infarction and so to provide a paradigm which may identify patients who were candidates for aneurysm formation. METHODS: Of the patients who underwent coronary angiography during the interval between 1995 and 2000 in our clinic, 809 were found to have anterior MI and LVA (aneurysm group) (677 men, 132 women, mean age 53.3+/-11.4 years). The clinical and the angiographic data of these patients were compared with those of 446 patients (399 men, 47 women, mean age 55.2+/-10.5 years) with previous anterior MI and without LVA (control group). RESULTS: LVA was found to occur more frequently in females (16.3% in women and 10.4%, in men, P=0.03) and in patients without previous angina (23.5 vs. 8.2%, P<0.0001). Major cardiovascular risk factors, previous anti-anginal medication and thrombolytic therapy did not show a significant difference between the two groups. Angiographic examination revealed that single-vessel disease, proximal left anterior descending artery (LAD) stenosis, total LAD occlusion, mean stenosis in LAD artery, end-diastolic pressure and left ventricular score were all higher in the aneurysm group compared to control group. After adjustment for other clinical and angiographic variables, single-vessel disease [odds ratio (OR) 5.89, 95% confidence interval (CI)=3.68-9.28, P<0.0001), absence of previous angina (OR=4.21, 95% CI=2.1-7.48, P=0.0003), total LAD occlusion (OR=2.63, 95% CI=1.97-3.53, P<0.0017) and female gender (OR=1.60, 95% CI=1.20-2.28, P=0.043) remained the independent determinants of LVA formation after anterior MI. CONCLUSION: In patients with LVA, logistic regression analysis revealed that (1) single-vessel disease, (2) absence of previous angina, (3) total LAD occlusion and (4) female gender were independent determinants in the formation of LVA after anterior MI. Coronary collateral status and risk factors, such as hypertension, diabetes mellitus, hypercholesterolemia, smoking and family history of CAD were not found to be important determinants in the aneurysm formation.