Study On Efficacy Of Endodermis Functional And Intra-medio Layer Thickness Of Carotis Of Intensive Lipid Lowering With Atorvastatin In High Risk Coronary Heart Disease

Background: Coronary atherosclerosis heart disease (CHD) is a disease caused by several risk factors with high morbidity and mortality, especially in the population with high risk factors. For the past few years, the emphasis of how to prevent and cure CHD has been transfer to first and second class prevention. There are studies indicated that endodermis functional impairment is the labeling of the preclinical phase of CHD,and the intra-medio layer thickness augment of carotis has been as the independent risk factor of morbidity and fatality in the CHD pationt. Atorvastatin as a new type tissue selectivity 3-hydroxy-3-methyl glutaryl CoA reductases-stat,can lower TC and LDL-C, and educe its non-lower lipin effection,improve endodermis functional impairment,lower platelet aggregation and lesson angio-inflammatory, should lower the morbility of CHD,coronet arteries even and elevate survival effectively.Objective: Investigate the effection of Intensive Lipid Lowering and routine Lipid Lowering With Atorvastatin in HighRisk Coronary Heart Disease, to the endodermis functional and intra-medio layer thickness of carotis. Methods: selection critria: Patients with high CHD risk facotrs in our hospital between March 2005 and october 2006 were enrolled in the study .High CHD risk was defined as CHD and CHD risk equivalent. CHD risk equivalent is defined a person without established CHD, whose absolute 10-year risk for developing major coronary events (myocardial infarction and coronary death) is equal to that of persons with CHD, i.e, >20 percent per 10 years. CHD equivelant include (1). diabetes, (2). other forms of clinical atherosclerotic diseases (peripheral arterial disease, abdominal aortic aneurysm, carotid artery disease), (3). high-risk persons with multiple risk factors who can be diagnosed CHD, or with 10-year risk>20 percent ; and with LDL cholesterol level≥3.4mmol/L. They all did not received statins four weeks before treatment, and the eighty-one patients aged 45 to 78 years (48 male and 32 female). Average age is(63.82土8.69).Exclusion critria: pregnancy or breastfeeding women, primary hypothyroidism (TSH>5.5mU/L), nephrotic syndrome or renal disfunction, blood urea nitrogen (BUN)≥10.71mmol/L (30mg/dL) or serum creatinine(Cr)≥176mol/L (2.0mg/dL), obstructive biliary disease, active liver disease, chronic viral hepatitis or hepatic disfunction, Alanine aminotransferase(ALT) or Asparatate aminotransferase (AST)≥3 times upper limit of normal or Hyperbilirubinemia, myopathies, creatine kinase(CK)>5 times upper limit of normal or creatine kinase >upper limit of normal that its cause was indefinitely, alcohol or drug abuse, participation in another study within 1 months before randomization or concomitant use of the following drugs: lipid-lowering agents expect for the study medication, immunosuppressants, any drugs known to affect lipid levels or drugs that interfere with study medication or drugs that affect clinical laboratory parameters (e.g., systemic steroids or isotretinoin, erythromycin), drugs associated with rhabdomyolysis in combination with statins,severe lung disease, malignant tumor (with exception for skin cancer that can be cured), chronic pancreatitis,collagenoses.The patients were randomized into 10mg/d atorvastatin group (in all 40 patients, 25 male and 15 female, with age of 63.56土8.47 years) and 40mg/d atorvastatin group(in all 41 patients, 24 male and 17 female, with age of 64.13±8.04 years).The patients of two groups received atorvastatin orally once at night leaving diet habit, lifestyle and other medical treatment unchanged. Patients were permited to decrease atorvastatin dosage or withdraw from the trial if their ALT or AST≥3 times upper limit of normal and CK>10 times upper limit of normal .TC, LDL-C, HDL-C, TG, Glucose, creatine kinase,hepatic function and renal function were measured regularly before study entry and at month 1, 3, 6 during the study period. TG,TC,GLU,CK,hepatic function and renal function by enzymic method determined at hol- automatic biochemistrict meter and HDL-C by immunoturbidimetry. LDL-C were measured by Formula of Friedewald: LDL-C=TC - HDL-C - TG/2.2 (LDL-C dose not adopt the Formula if value of TG >4.52mmol/L, LDL-C by immunoturbidimetry). All the patients were not suitable eat high fat diet and drinking pro-evening ,inadvisable eating after dinner, must fast over 12 hours before the venous blood samples were obtained every time.Determin the variation of diastolic function mediated by arteria brachialis bloodstream, at pretherapy and post-treatment six and twelve month. These determinion apply germany SEQUOIAS-512 type diagnostic ultrasound meter, Celermajor and reference Celermajor method. Patients take dorsal position, abducens right upper extremity fifteen degrees, portait scan arteria brachialis above elbow with 2D-ultrasonic imaging, measure vertical dimension of circa endomembrane in ventricular diastasis, measure three cardiac cycle,take general average,is arteria brachialis inner diameter. Every subjects measure its arteria brachialisinner diameter in ground condition and after reactive hyperemia. Subjects recess ten mintues before test, march reactive hyperemia test after ground value(D0) was determined,put the blood pressure gauge cuff in below elbow, charge and pressurize to 300mmHg, deflate and deboost after four minute,measure arteria brachialis inner diameter in 60~90s( D1) represent。The change of inner diameter after reactive hyperemia (D1-D0)/D0*100%, represent blood vessel diastolic function dependented by arteria brachialis endodermis (FMD). In these test process, supersound transducer be in fixed position,and take same place in every time.Determin the variation of the intra-medio layer thickness of carotis, at pretherapy and post-treatment six and twelve month. These determinion apply germany SEQUOIAS-512 type diagnostic ultrasound meter,take test with two sides carotid by special messenger, transducer frequency is 7.0MHZ. Patients take supine position, explorate arteria carotis communis transversally from clavicular wall, fix the picture below one centimeter of bulbus caroticus in ventricles diastasis(i.e synchronization ECG wave), measure three cardiac cycle every side, the arteria carotis communis posterior wall appearant two strip parallel bright line separated by relative lower level echo,take vertical dimension in between, calculate average value of six times of the carotid's two sides,this is the intra-medio layer thickness of carotis(IMT),IMT≥0.9mm is thickening.Chief complaints such as vertigo, myalgia, gastrointestinal events were recorded durng the follow-up.All statistical tests were performed with two-sided alternatives and a typeⅠerror of 0.05 and with the use of SAS software (version 6.12). Initially the homogeneity of variance among all the groups was analyzed. All the measurement data was expressed as mean±standard deviation (mean±SD) and students t test was used to explore statistical significance. Chi-square test was used for analysis of categorical data.Results: 1 The two groups of patients were well matched with regard to baseline characteristics of age, sex,disease variety and body mass index (P>0.05) (Table 1).2 After 1, 3, 6 months treatment, TC, LDL-C, TG were significantly reduced striking (P<0.01) and HDL-C was increased (P>0.05) compared with baseline in two groups (Table2). Two sets group comparison:Atorvastatin of 40mg yielded significantly reduction from baseline in LDL-C compared with Atorvastatin 10mg at month 1(40.78% vs 31.71%; P<0.05), at month 3 (47.17% vs 36.27%; P<0.01) and at month 6 (49.14% vs 38.04%; P<0.01) respectively. The data also showed there was a significant recuduction in TC in the group given atorvastatin 40mg daily compared with the group given atorvastatin 10mg daily after1-month treatment (32.83% vs 25.13%; P<0.01), after 3-month treatment (36.85% vs 28.01%; P<0.01) and after 6-month treatment (37.69% vs 29.37%; P<0.01). However, there was no significant reduction in TG between two groups at month 1(21.69% in atorvastatin of 40mg/day group vs 15.95% in atorvastatin of 40mg/day group; P>0.05), month 3 (26.79% in atorvastatin of 40mg/day group vs 19.68% in atorvastatin of 10mg/day group; P>0.05), and month 6 (26.98% in atorvastatin of 40mg/day group vs 20.74% in atorvastatin of 10mg/day group; P>0.05), respectively. There was also no significant difference in HDL-C between atrovastatin 40mg daily group and atrovastatin 10mg daily group after 1-month treatment (2.61% vs 4.27%; P>0.05), after 3-month treatment (3.48% vs 5.13%; P>0.05) and after 6-month treatment (3.48% vs 5.98%; P >0.05).3 After treatment in six and twelve month, FMD of the two sets improved obviously all compare to pretherapy P<0.05,compare to six month , the FMD of twelve month improved obviously P<0.05.Two sets group comparison: .after treatment in six and twelve month, FMD of the 40mg/d group improved obviously P<0.05. (Table 3)4 After treatment in six month, IMT of the 10mg/d group has improved compare to pretherapy,but without statistics difference P >0.05,compare to pretherapy and six month treatment, the twelve month treatment improved obviously P<0.05。After treatment in six and twelve month, IMT of the 40mg/d group improved obviously compare to pretherapy P<0.05,compare to six month , the IMT of twelve month improved obviously P<0.05。Two sets group comparison: .after treatment in twelve month, IMT of the 40mg/d group improved obviously P<0.05 (Table 3)5 Mono-agentcorrelation analysis display that , the baseline numerus of FMD and IMT without correlativity(r=0.0685,p>0.05);After treatment in six month of the two sets , the improved degree of FMD and IMT have no correlativity with the depressed degree of LDL-C(r= -0.06 p>0.05;r=0.1188,p >0.05)(Fig.1,2,3)6 During study period, the data showed both groups had a similar safety profile. The proportion of patients with elevation of ALT and AST was slightly high in the group given atorvastatin 40mg/day during the study period, However, there was no stastical significance. CK level in all patients was in normal limit during the study period. Rhabdomyolysis was not observed in both groups. There was no siginifcant difference in adverse effects between both groups (P>0.05) (Table 4).Concolusions: For patients with high CHD risk factors, Atorvastatin at 40mg/day is more effective in Lipid-modifying compared with atorvastatin 10mg/day,and educe its non- lipid-modifying effect more effective in the same time, reverse or delay the proceeding of the carotid's IMT,improve endodermis fuction.And the improved fuction to endodermis fuction and carotid's IMT are independent to Lipid-modifying. However, safety was similar in two groups.