Effects Of Fluvastatin On Serum SICAM-1 And SVCAM-1 In Patients With Heart Failure

Congestive heart failure (CHF) was a common clinical syndrome of cardiovascular system, the serious or terminal stage of various cardiovascular diseases and major causes of death, has a high mortality rate. Modern pathophysiology hold the opinion that there are two major factors related to the occurrence of CHF, namely, cardiac remodeling (ventricular remodeling) and neuroendocrine activation. There is a wide range of endogenous neuroendocrine and cytokine activation after the initial myocardial injury, which increased in both organizational and cycle levels. Over-expression of the vasoconstriction substance caused by the startup of cytokines and neuroendocrine trigger inflammatory response together, and accelerated the apoptosis of myocardial cells. Long-term and chronic activation of Neuroendocrine-cytokines system accelerate the cardiac remodeling and increase the myocardial damage and the deterioration of cardiac function, which further activate neuroendocrine-cytokines system, so that form a vicious cycle and cause continuous worsening of CHF.Cell adhesion molecules (CAM) is a glycoprotein of the membrane surface which mediated the adhesion effect between cells and cells, cells and extracellular matrix. Mainly expressed in the cell surface of endothelial cells, leukocyte, platelets and smooth muscle, a little exist in plasma in soluble form. It plays an important role in many physiological and pathological processes, such as embryonic development and differentiation, the maintenance of normal tissue structure,inflammation and immune responses, wound recovery, blood coagulation and thrombosis, as well as tumor invasion and metastasis, and so on. They play an important role in the adhesion and activation between leukocyte and vascular endothelial cells, especially microvascular endothelial cells, participate in the occurrence and development of many diseases. CAM may play an important role in the formation and development of CHF, as it has an important and regulatory function of interactions between cells and cell. CAM shed from the leukocytes, vascular endothelial cells or other cell surface into the blood, then become soluble cell adhesion molecules (sCAM). In recent years, clinical and basic experimental study show that in the process of CHF there is a expression of sCAM and a marked increase in plasma levels, maybe one of the important reasons of myocardial cells failure. So further study the molecular mechanism of CHF have great significance to curb the occurrence and development of CHF.A great deal of researches has confirmed the significant and lasting existence of all kinds of serum inflammatory factors in CHF patients. soluble intercellular adhesion molecule -1 (sICAM-1) and soluble vascular cell adhesion molecule -1 (sVCAM-1) were the cell adhesion molecules which study more in CHF, belong to immunoglobulin superfamily, they have important function of regulated the interactions between cells and cell, they play an important role in the adhesion and activation between leukocyte and vascular endothelial cells, especially microvascular endothelial cells. ICAM-1 is an indispensable substances of neutrophil migration, aggregation and exert cytotoxicity, participate in the occurrence and development of many diseases. The surface of myocardial cells membrane create a large number of ICAM-1 under the act of hypoxia, cytokines and other factors, lymphocyte function-associated antigen (LFA-1) was the ligand of ICAM-1 what distributing at the surface of neutrophils, combination of the pair of adhesion molecule promote the adhesion of myocardial cells and neutrophil, and then neutrophils exert cytotoxic activity, release cytolytic substances such as perforin cause the myocardial necrosis.In addition to the effect of lipid-lowering, Statin drugs not only have multiple effects which not depended on the cholesterol lowering, such as anti-inflammatory response,improve endothelial function, plaque stability, anti-arrhythmias, inhibit thrombosis, anti-fibrosis and inhibition of neuroendocrine activity, but also significantly reduce the incidence of cardiovascular events and mortality. Series of studies found that statin drugs can significantly reduce the level of serum sCAM in the treatment process of coronary heart disease and hyperlipidemia, but there is no relevant clinical study to show the effects of statin drugs on the levels of in vivo sCAM in CHF patients.To sum up, with the development of a large number of clinical trials and basic research, importance of inflammatory response in CHF gradually been recognized. There were significant increase of sICAM-1 and sVCAM-1 serum levels in the process of CHF, suggesting that they are the important information of activation of related immune system, and maybe one of the important reasons which cause functional failure of myocardial cell. To Reduce the sCAM over-expression and the serum levels will become the important aspect of the therapy of CHF in the future, must provide more new ways of prevention and treatment in CHF.In this study, through observing the effect before and after fluvastatin therapy on the serum sICAM-1 and sVCAM-1 changes in CHF patients, to investigate the effect of fluvastatin in the process of CHF treatment.ObjectiveThe present study mainly observe the effects of short-term treatment of fluvastatin on serum sICAM-1 and sVCAM-1 in patients with CHF, and investigate the effects of fluvastatin on the treatment of CHF,to provide more clinical basis for the diagnosis and treatment of CHF.Methods70 CHF patients were Selected from Department of Cardiology of Kai luan Limited liability company Hospital of North China Coal Medical University during June 2007~July 2008, all cases are consistent with the Framinghan heart failure diagnosis standards. NYHA classification was used to classify cardiac function, 7 cases with cardiac function classⅡ, 35 cases with cardiac function classⅢ, 28 cases with cardiac function classⅣ, among all CHF patients, 33 cases with ischemic cardiomyopathy, hypertensive heart disease was 21 cases, 9 cases with age-related valvular heart disease, dilated cardiomyopathy was 7 cases. Patients who have been Selected were randomly divided into 2 groups, conventional therapy group was 33 cases, intervention group was 37 cases. All patients were ruled out diabetes, thyroid dysfunction, rheumatism, chronic obstructive pulmonary disease, cerebrovascular accident, acute myocardial infarction within 6 months, pregnancy, cancer, liver and kidney function obvious abnormalities and other diseases. 20 cases of normal control group are selected from the healthy people, gender and age has no significant difference to other two groups.Cardiac function of CHF patients were classified according to NYHA criteria after selection, all were administerd color Doppler echocardiography examination and routine biochemical testing. Conventional treatment group was conventional administerd diuretics, angiotensin converting enzyme inhibitors (ACEI), digoxin,β-receptor blocker as drug treatment, and the intervention group at the basis of conventional treatment group add up with fluvastatin (brand name: Lescol, Novartis Pharma Ltd. Production) 40mg, take medicine at 20:00 every night, observation of two weeks. To observe the changes of clinical symptoms and signs before and after the treatment, and at the same time use the enzyme-linked immunosorbent assay (ELISA) measured serum sICAM-1 and sVCAM-1 levels before and after treatment in patients with CHF.Set up the database with Excel 2003 after all the information were verified and organized, using SPSS for Windows 13.0 statistical software for statistical analysis. Measurement data were expressed by both the average and the standard deviation (x±s). firstly, give data of every group normality and homogeneity of variance test, comparison before and after treatment using paired t test, comparision between groups using two-sample t testing, comparision of multiple averages use of one-way ANOVA, look P <0. 05 as the difference has statistical significance.Results1. The serum sICAM-1 and sVCAM-1 levels have not Statistical significance in CHF patients with different etiology (P> 0.05).2. Serum sICAM-1 and sVCAM-1 levels in patients with cardiac function classⅣwas significantly higher than patients with heart function classⅡandⅢ(p <0.05), and the comparison between cardiac function classⅡandⅢhave not Statistical significance (P> 0.05), all patients have an average higher than normal control Group (p <0.05).3. Serum sICAM-1 and sVCAM-1 levels of conventional treatment group and intervention group have significant decrease after treatment (p <0.05), however, inter-group comparison of the decreased degree has no statistically significance .Conclusions1. Serum sICAM-1 and sVCAM-1 levels were not related to the cause of CHF.2. Serum sICAM-1 and sVCAM-1 levels of CHF patients are mainly related to the degree of cardiac function.3. On the basis of conventional treatment together with short-term fluvastatin treatment can not further reduce the sICAM-1 and sVCAM-1 levels.