Early initiation of low-dose atorvastatin treatment after an acute ST-elevated myocardial infarction, decreases inflammatory process and prevents endothelial injury and activation.

BACKGROUND: High-dose statin treatment improves clinical outcome of ST-elevated myocardial infarction (STEMI). However, the effect of low-dose atorvastatin treatment on inflammatory and pro-thrombotic molecules during the post-STEMI period is unclear. We investigated the effect of low-dose atorvastatin treatment on the kinetics of cytokine IL-6, vascular cell adhesion molecule (sVCAM-1) and endothelium-derived markers of thrombosis/fibrinolysis such as von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (tPA), post STEMI. METHODS: Twenty-four normocholesterolemic patients with STEMI were randomised to receive atorvastatin 10mg/day or no statin treatment for 6 weeks after the event. Blood samples were obtained by their admission to the hospital as well as at weeks 1 and 6. Circulating levels of IL-6, sVCAM-1, vWF, PAI-1 and tPA were determined by ELISA. RESULTS: Atorvastatin induced a decrease of IL-6 at 1 week, an effect which reached significance compared to baseline at 6 weeks post STEMI (p<0.05 vs baseline). Serum sVCAM-1 was increased in controls both at 1 and 6 weeks post-STEMI (p<0.05 vs baseline), an effect prevented by atorvastatin. Plasma vWF was increased 1 week post-STEMI in controls (p<0.05 vs baseline) and returned to baseline at 6 weeks, an effect prevented by atorvastatin. Plasma PAI-1, tPA and the PAI-1/tPA ratio remained unchanged in both groups. CONCLUSION: Early initiation of low-dose atorvastatin treatment decreases the expression of IL-6 and sVCAM-1 and the release of vWF in patients with STEMI. Therefore, low-dose atorvastatin, modulates inflammatory response and decreases endothelial injury and activation in patients with recent STEMI.

Effects of insulin dependence on inflammatory process, thrombotic mechanisms and endothelial function, in patients with type 2 diabetes mellitus and coronary atherosclerosis.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is characterized by endothelial dysfunction, increased thrombogenicity and abnormal inflammatory response. HYPOTHESIS: We hypothesizsed that insulin dependence/exogenous insulin administration may affect thrombotic/inflammatory status and endothelial function in patients with T2DM and coronary artery disease (CAD). METHODS: Fifty-five patients with T2DM + CAD (26 insulin-treated (INS) and 29 under oral biguanide + sulphonylurea (TABL)) were recruited. Endothelial function was assessed by gauge-strain plethysmography, and serum levels of inflammatory and thrombotic markers were determined by enzyme linked immunosorbent assay. RESULTS: There was no significant difference in endothelium-dependent dilation (EDD) between the study groups, while EDD was correlated with fasting glucose levels in both INS (r = - 0.776, p = 0.0001) and TABL (r = - 0.702, p = 0.0001). Patients in INS group had higher levels of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), monocyte chemoattractant protein (MCP-1) and vascular cell adhesion molecule (sVCAM-1), compared to TABL. However, TNF-alpha was negatively correlated with protein C (PrtC) only in INS (r = - 0.726, p = 0.01) but not in TABL group (r = - 0.066, p = 0.738). Similarly, sVCAM-1 was correlated with PrtC only among INS patients (r = - 0.451, p = 0.046) but not in TABL (r = 0.069, p = 0.727). In multivariate analysis, insulin dependence was a predictor of IL-6, TNF-alpha, MCP-1 and sVCAM-1 levels independently from the patients' demographic characteristics, the angiographic extend of CAD or the duration of diabetes. CONCLUSIONS: Insulin treatment in patients with type 2 diabetes mellitus affects the expression of inflammatory cytokines and subsequently modifies the thrombotic mechanisms in patients with coronary atherosclerosis, independently from the duration of diabetes and the extend of coronary artery disease.

Differences in inflammatory and thrombotic markers between unstable angina and acute myocardial infarction.

BACKGROUND: Unstable coronary syndromes are characterised by increased inflammatory process and endothelial activation. However, the underlying mechanisms of the acute coronary syndromes are still obscure. We evaluated the differences of inflammatory and thrombotic markers, at the acute phase of unstable angina (UA) and acute myocardial infarction (AMI). METHODS: The population of the study consisted of 216 subjects: 136 patients with UA, 57 patients with AMI and 23 healthy controls. Blood samples were taken by their admission to the hospital. Inflammatory and thrombotic markers were measured by ELISA. RESULTS: Patients with UA had significantly higher levels of interleukin-6 (IL-6), soluble vascular cells adhesion molecule (sVCAM-1) and von Willebrand factor (vWF) (p<0.05 vs controls), and lower levels of antithrombin III (ATIII) (p<0.01 vs controls) and protein C (PrtC) (p<0.05 vs controls). Similarly, patients with AMI had higher levels of IL-6, sVCAM-1, vWF and tissue plasminogen activator (tPA) (p<0.01 vs controls) and lower levels of ATIII (p<0.01 vs controls) and prtC (p<005 vs controls). Patients with AMI had significantly higher levels of vWF, tPA and sVCAM-1 compared to UA patients (p<0.05). CONCLUSIONS: Patients with unstable coronary syndromes had increased levels of IL-6, sVCAM-1 and vWF as well as decreased levels of ATIII and PrtC by their admission. However, patients with AMI had higher levels of all the endothelium-derived inflammatory (e.g. sVCAM-1) of thrombotic/fibrinolytic (e.g. tPA and vWF) markers, compared to those with UA. These findings imply that patients with myocardial infarction show further increase of endothelium-derived inflammatory and thrombotic markers compared to patients with unstable angina, in response to a similar proinflammatory stimuli.

Effects of early administration of atorvastatin treatment on thrombotic process in normocholesterolemic patients with unstable angina.

BACKGROUND: Although statin-treatment during the acute phase of unstable coronary syndromes improve the outcome their effects on thrombosis/fibrinolysis system in normocholesterolemic patients admitted with unstable angina remain obscure. We assessed the effects of short-term atorvastatin treatment on thrombotic/fibrinolysis markers in normocholesterolemic in patients with unstable angina. METHODS: Forty-five patients with unstable angina were allocated into two groups to receive atorvastatin 10 mg/day (n = 24) or no statin (n = 21) for 6 weeks. Circulating levels of von Willebrand Factor (vWF), factor V (fV), protein C (prC), tissue plasminogen activator (tPA) and antithrombin III (ATIII) were measured by enzyme linked immunosorbent assay, by the patients admission and at the 1st and 6th week of the study. RESULTS: After 1 week of treatment, a significant increase of ATIII (p < 0.05), fV (p < 0.01) and vWF (p < 0.05) was found in the control group, but not in atorvastatin-treated group. Similarly, at 6 weeks after admission, plasma levels of ATIII were still significantly higher than at baseline in controls (p < 0.05), but not in atorvastatin-treated group. Plasma levels of PrtC were significantly increased in both controls (p < 0.01) and atorvastatin-treated patients (p < 0.05) at 1 week, while remained unaffected in atorvastatin-treated group at 6th week. There was no significant difference in the variations of plasma levels of tPA, PrtS and fVII between the two groups at 1 and 6 weeks after admission. CONCLUSIONS: In normocholesterolemic patients admitted with unstable angina the early administration of atorvastatin, significantly affects von Willebrand factor levels and the expression of liver-derived components of both thrombosis and fibrinolysis system.

The impact of early administration of low-dose atorvastatin treatment on inflammatory process, in patients with unstable angina and low cholesterol level.

BACKGROUND: Lipid-lowering agents are known to reduce long-term mortality in patients with stable angina or multiple risk factors. However, the effects of lipid-lowering treatment on inflammatory process during and immediately after the acute phase of unstable angina remain unclear. In this study we assessed the effects of low-dose atorvastatin treatment, on inflammatory process in patients admitted for unstable angina with low cholesterol level. METHODS: Forty-seven normocholesterolemic patients with unstable angina were randomized into two groups, and received atorvastatin 10 mg/day (n = 24) or no statin (n = 23) for 6 weeks. Circulating levels of inteleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor alpha (TNF-alpha) and soluble vascular cell adhesion molecule (sVCAM-1) were measured by their admission, and at the 1st and 6th week of the study. RESULTS: Serum levels of MCP-1 and sVCAM-1 were significantly increased in the control group (p < 0.05) while remained unaffected in the atorvastatin-treated group six weeks after admission. However, IL-6 and TNF-alpha levels were similarly decreased in both atorvastatin-treated and control groups. CONCLUSION: Low-dose atorvastatin treatment modifies inflammatory process in patients with unstable angina and low cholesterol level, an effect seen at 6 weeks but not 1 week after admission.

Vitamin C affects thrombosis/ fibrinolysis system and reactive hyperemia in patients with type 2 diabetes and coronary artery disease.

OBJECTIVE: To examine the effect of vitamin C on forearm vasodilatory response to reactive hyperemia and on plasma level of plasminogen activator inhibitor 1 (PAI-1), von Willebrand factor (vWF), tissue plasminogen activator (tPA), antithrombin III (ATIII), proteins C and S, and factors V (fV) and VII (fVII) in patients with both type 2 diabetes and CAD. RESEARCH DESIGN AND METHODS: A total of 39 patients with type 2 diabetes and CAD were divided into two groups and received vitamin C (2 g/day) or no antioxidant for 4 weeks. Forearm blood flow was determined using venous occlusion gauge-strain plethysmography at baseline and after treatment. Forearm vasodilatory response to reactive hyperemia (RH%) or nitrate (NTG%) was defined as the percent change of flow from baseline to the maximum flow during reactive hyperemia or after administration of nitrate, respectively. Biochemical markers were determined by enzyme-linked immunosorbent assay (ELISA) or other standard methods. RESULTS: RH% was significantly increased after treatment with vitamin C (from 62.4 +/- 7.2 to 83.1 +/- 9.3%, P = 0.024) but remained unaffected in the control group. Vitamin C decreased plasma levels of fV (from 143 +/- 5.4 to 123 +/- 6.03%, P = 0.038), vWF (from 133.5 +/- 14.5 to 109.5 +/- 11.4%, P = 0.016), and tPA (from 12.3 +/- 0.99 to 8.40 +/- 0.60 ng/ml, P = 0.001), whereas these levels remained unaffected in the control group. The changes in RH%, vWF, and tPA were significantly greater (P = 0.028, 0.036, and 0.007, respectively) in the vitamin C-treated group than in the control group. Levels of ATIII, proteins S and C, fVII, and PAI-1 remained unchanged in all groups. CONCLUSIONS: Short-term treatment with high doses of vitamin C improved RH% and decreased plasma levels of tPA and vWF in patients with type 2 diabetes and CAD.