| Objective: Unstable angina(UA) is commonest type ofacute coronary syndrome(ACS). EARISA trial reported that48% of the patients hospitalized for ACS was diagnosed as UA.Cardiovascular events typically arise from the disruption of theatherosclerotic plaques that contain numerous inflammatorycells. Inflammatory cells release cytokines that degradeextracellular matrix in the fibrous cap of atherosclerotic plaques.Activated inflammatory cells produce tissue factor thatpromotes thrombus formation by disrupted atheroma. Coronarythrombosis is now generally recognized as the precipitatingevent in the transition from stable to acute ischemic heart diease,manifested by UA, acute myocardial infarction, and suddendeath from coronary causes. Concentrations of C-reativeprotein(CRP) are directly correlated with the presence andseverity of coronary, cerebral, and peripheral arterialatherosclerosis. CRP is a representative acute phase reactantprotein. CRP is synthesized by liver and modulated by IL-6.Increases in the plasma concentrations of CRP have beenobserved in patients with severe UA. A plasma concentration ofCRP above 3 mg/l was associated with a significantly worseprognesis in patients admitted to hospital with UA. Furthermore,high-sensitivity CRP(hsCRP) is better to predict the risk of theheart events. Matrix metalloproteinases (MMPs) are a family ofZn2+ -dependent endopeptidases capable of cleaving componentsof extracellular matrix . MMP-9 plays a very important role inheart events. Evidences suggest that MMP-9 activity mayfacilitate atherosclerosis, plaque destabilization, and plateletaggregation. The endothelium plays a central role in maintainingcardiovascular homeostasis via the production and release ofvasoactive mediators such as endothelium-derived relaxingfactor(EDRF) and nitricoxide(NO). Endothelium dysfunctionthat produces less NO plays an essential role in thepathophysiology of coronary heart disease(CHD) especiallywith the initial and developmental process of atherosclerosis andthrombosis via the following possible mechanisms:(1)causingdefects in coronary artery vasomotion,(2) promoting the processof coronary arterial wall remodeling,(3) facilitating plateletactivation and aggregation,(4) accelerating monocyte andneutrophils activation and adherence. HMG-CoA reductaseinhibitors (stains) can reduce heart events of the patients withCHD. Stains can lower lipid, improve endothelium function,prohibit platelet activation and aggregation, stabilize plaque andprevent inflammatory cells produce. We study the effect ofdifferent-dose atorvastatin in early stage of the UA patients tofind whether higher dose atorvastatin is better than lower doseatorvastatin and their side effect.Method: A total of 90 patients(mean age 58.8+12 years,men 65, women 25) were selected consecutivly from September2003 to Octorber 2004. The inclusion criteria include as thefollowings: chest discomfort happen more and last longer in amonth and chest discomfort occur with a duration of at least 15minutes and with the most recent occurrence ≤24 hours beforehospital admisson; the diagnosis of UA required new ordynamic ST-wave or T-wave changes in at least 2 contiguousECG leads or a new wall motion or myocardial perfusionabnormality and no elevation in the serum creatine kinase. Thecriteria for exclusion include a myocardial infarction within theprevious month, coronary artery bypass surgery within thepreceding 3 months, revascularization by coronary catheterintervention within the preceding 6 months, an elevated creatinekinase, intercurrent inflammatory or neoplastic conditions likelyto be associated with an acute-phase response, valvular heartdisease, NYHA cardiac function classification≥3, patient'sserum transaminase levels increase to >3 times the upper limitof normal and using HMG-CoA reductase inhibitors recently. Ifa patient develops muscle pain, weakness, or tenderness inassociation with a serum creatine kinase level>10 times upperlimit of normal, the study medication is discontinued. Patientswere randomized to three groups: group 1(28 patients) taking noatorvastatin(lipitor); group 2(32 patients) taking lipitor 10mg/d;group 3(30 patients) taking lipitor 20mg/d. All patients weretaking aspirin, nitrate, angiotensin converting enzyme inhibitor,Low Molecular Heparin,β-blocker if they needed. Bloodsamples of all the cases was got after 12 hours fasting afterhospitalized and 10 days later of treatment. Then the serum orplasma was separated and put into laboratory for storage at–80 ℃. All the sample was tested TC,TG,HDL-C,LDL-C,ALT,CK,NO,MMP-9 and hsCRP. A SAS software was used forstatistical analysis, and p value ≤0.05 was consideredstatistically significant.Results: Baseline Characteristics of the Patients did notdiffer among the 3 groups. Ten days later compared with controlgroup, lipitor(10 mg/d) and lipitor(20 mg/d) was associated witha great reduction in TC and LDL-C (P<0.05); Lipitor (20mg/d)had a greater reduction in TC and LDL-C than lipitor(10mg/d)(P<0.05). After 10 days of treatment,TG was graduallyreduced and HDL-C and NO was gradually increased with theincreasing dose of lipitor, but there was no significantlydifferent in the 3 groups(P>0.05). There is no significantlydifferent in CK of the 3 groups after 10 days treatment.Compared with control group, lipitor(10 mg/d) and lipitor(20mg/d) was associated with a great reduction in MMP-9 (P<0.05)after 10 days treatment; Lipitor (20mg/d) had a greater reductionin MMP-9 than lipitor(10 mg/d)(P<0.05). Compared withcontrol group, lipitor(10 mg/d) and lipitor(20 mg/d) wasassociated with a great reduction in hsCRP(P<0.05) after 10days treatment but there is no different in hsCRP between thetwo group. Compared with control group , lipitor(10 mg/d)and lipitor(20 mg/d) was associated with a great increasing in... |
