Effects Of Different Dosage Of Atorvastatin On Inflammatory Response, Platelet Activity And Fibrinolytic Activity Of Patients With Acute Coronary Syndrome

Background and ObjectiveAcute Coronary Syndrome(ACS), is a kind of acute myocardial ischemiasyndrome, in which breakage or erosion of unstable arteriosclerostic plaquethrombrosed finally intiating actue myocardial ischemia syndrome, including unstableangiona, non-ST-segment elevation myocardial infarction(NSTEMI) and ST-segmentelevation myocardial infarction (STEMI). The process of ACS occurrence,development and result is a series of patho-physiological changes, includinginflammation response, intemal changes of platelet activity and coagulationfibrinolytic activity.As researches show, in some pateints of ACS, the narrowness of coronary wasusually slight or mediate, rather than severe. The occurance of severe clincal affairswas due to the activity changes of arterial plaque, in which acute inflammatoryresponse factors play a critical role. Further evidences demonstrte that the activitedinflammatory cells are important factors in the process of plagues changeing fromstableness into breakage, rather than that breakage of plagues activiting inflammatorycells. Meanwhile, inflammatory responces activity in vivo is an correlative strongly index for prognosis of ACS patients.This research take hs-CRP, IL-6 as reliable indexs to observe the inflammatoryresponces activity. The concentration of CRP is correlative colsely with acuteinflammation process of ACS and can reflex the activity of inflammation response.IL-6 is a kind of pro-inflammtory cytokine. It is not only the risk index of ACS, butalso an index of prognosis. And owing to the correlativity of IL-6 and CRP, IL-6 andCRP were detected, observed and analysed altogether in the research to ensure theconclusion.Formation of thrombose is the pathophysiologic basis of ACS. Endothecialinjury and dysfunction in the athrotic plagues activate the platelet adhesion andformation of white thrombose and appear cliniclaly to be UA and NSTEMI.Activation of platelet provides solid phase for initiation of intrinsic blood coagulationsystem and accelerates formation of thrombin, turning fibrinogen into fibrin whichtwining red blood cells and forming into red thrombose, which appear cliniclaly to beSTEMI.Over-activation of platelet is not only a factor leading to blood vessal disease butalso initiation and cascade mechanism of acute thrombose affair. Activated plateletincurs inflammation and thrombrose through action of adhesion and activatedneuphocyte and endothycyte. So, recognizing the function of platelet is crucial for thetreatment of ACS.The balance between the physiologic activator of fibrinolytic system (t-PA) andthe inhibitor of t-PA—PAI (especially PAI-1) determines the situation of fibrinolyticsystem. Enhancement of PAI-1 and inhibitation of t-PA can downregulate fibrinolyticsystem and induce the formation of thrombus. Evidences have already demonstratethe close relation between PAI-1 level and occurance of coronary heart disease.Meanwhile, research results manifest that PAI-1 level reaches peak and t-PA level deline to bottomline, and coagulation mechanism becomes dominant 24 hours afterAMI. So, in one hand thrombus is easily formed on the basis of coronaryarteryatherose, and on the another hand, solution of blood clot is delayed, so the twofactors aggravte MI.Evidence manifest that Tatins(HMG-CoA inhibitor) have some functions ofanti-inflammation, anti-activation of platelet, regualation of fibrinolytic systemactivtity as well as degrade lipid level. Clinically, application of Atorvastatin explorea new era of treatment of coronary heart disease, called "Tatin revolution". It isreported that application of Atorvastatin can decrease the mortality rate 29%-38%.But there is still some debates on the dosage and salty of early aggressive lipidlowering treatment on ACS. The presenting researches take ACS patients as object tomeasure TC, hs-CRP, IL-6, TXB₂, GMP-140, PAI-1 level and t-PA activity inperipheral blood. The effect of different dosage of Atorvastatin on the blood levels isinvestigated to search mechanism and safety of aggressive lipid lowering treatment byAtorvastatin on prevention and treatment on ACS.Methods65 cases of unstable angina and acute myocardial infarction patients, diagnoseswere made according to ACC/AHA standard. On the first day of administration, 16mlvenous blood was taken. 10mg/d, 20mg/d, 40mg/d Atorvastatin were taken beforesleeping besides routine treatments of asprine and clopidogrel. After 14 days, 16mlvenous blood was taken, hs-CRP was measured by late immune enhancedtarbidimetry, IL-6, TXB₂, GMP-140, t-PA, PAI-1 were measured by ELISA. TC andAST, ALT, CK were measured by Automobile Olypropas. SPSS 13.0 statisticalsoftware was used to compare the data ofpre-treatment and after-treatment.ResultsTC, hs-CRP, IL-6, TXB₂, GMP-140, PAI-1 decreased significantly in all three groups, while t-PA activation increased remarkably. And after the treatment, therewere significant differences among three groups on TC, hs-CRP, IL-6, TXB₂,GMP-140, t-PA, PAI-1. But no visible statistics different of CK,AST,ALT amongthree groups.ConclusionsAtorvastatin perform active role to regulate blood lipod, inflammation response,platlet activity, fibrinolytic activity, and increase the function as the increase of dosein certain extension, and have good safety at the same time. To some extent, thisexplains that lipod decrease and anti-infammation, control activity of platelet,regulation of fibrinolytic activity are also the important mechanism of Atorvastatin ontreatment of ACS. And it also provide theory basis for the aggressive lipid loweringtreatment of ACS.