| 1. IntroductionVascular endothelium is an active endocrine organ. It secrets and expresses various important bioactive chemicals. Along with the progressive study on cardiovascular disease, endothelium has brought more and more interest and concern. The Vascular endothelium is an active endocrine organ. It secrets and expresses various physiological functions of endothelium mainly include: 1) adjust vasomotion; 2) prevent platelet adhesion and thrombosis; 3) modify the growth and proliferation of vascular smooth muscle cells; 4) prevent leukocyte infiltration and invasion of toxic chemicals. Endothelium dysfunction can cause over or abnormal expression of endothelium-derived vasoconstriction factor, such as endothelin (ET), inflammatory response in vascular wall, activation of platelet, and thrombosis. Meanwhile, C-reactive protein (CRP), as a circulating marker of inflammation, and CD62p, as a marker of platelet activation, can increase significantly. Statins has been widely used fortreatment of high cholesterol. Several large-scale clinical trials have shown that statins can reduce 30% of the incidence of major coronary heart disease events. The possible mechanisms of its protection on cardiovasculature include enhancing endothelium functions, anti-inflammation, inhibiting the proliferation of vascular smooth muscle cells, preventing platelet thrombosis, and stabilizing the artery plaques. In this study, the effects of simvastatin (a member of statins family) on the plasma levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), CRP, ET, and CD62p, as well as benefits to carotid atherosclerosis were examined during the treatment of hyperlipidemia using simvastatin. The study is aimed to 1) investigate the protective effects of simvastatin on endothelium and its clinical efficacy on the treatment of carotid atherosclerosis, 2) the dose effect of simvastatin on lowering cholesterol and the above parameters, and its clinical significance.2. Material and MethodsSubjects - Patients hospitalized in the department of cardiology, Shaoxing People' s Hospital from January 2002 to September 2003, were chosen. Patients with any of the following conditions were excluded: any liver disease, renal insufficiency, surgical trauma, myocardial infarction, infection, fever, using anti-inflammatory or anti-platelet adhesion medicine. Eligible patients had TC > 5. 7 mmol/1, and/or LDL-C > 3. 38 mmol/1. Total of 258 included patients were randomly assigned to 10 mg/day simvastatin, 20 mg/day simvastatin, or control groups.Methods - Single-blind test was designed. Multiple comparison, and comparison with its own methods were used in this study. All the patients were asked for their disease history, previous medication, and disease diagnosis. Levels of TC, and LDL-C were assayed by routine laboratorytechniques with the use of assay kits from Beijing Huaying Biotechnology Inc. Level of ET was measured using radio-immunohistochemistry with kids provided by Dade Behring Inc, USA. CRP was assayed by rate nephelometry. The positive expression of CD62p was determined by a flow cytometry (Beckman-Coulter, USA). Blood ultrasound measurement was performed using a colored Doppler ultrasound machine (Sequoia 512, Acuson Inc., USA) by ultrasound specialists. Patients were put in supine position with neck fully exposed. The region for scanning on carotid artery was between 4 cm before and 1.0 cm after the common carotid artery bifurcation towards external and internal carotid artery. Plaques were characterized as those protrusions in carotid artery wall showed in ultrasound echo structure, and the thickness > 1.3mm. Soft plaques were defined that their atherosclerosis plaque echoes are weaker than vessel wall echo. The thickness and number of soft plaques were recorded and semi-quantified to different grade levels using Xu et. al methods: 0 grade - no plaques, I grade - single-side plaque, thickness < 2 mm; II grade - single-side plaque, thickness > 2 mm, or both sides have plaques, but at least thick...
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