Long-Term Effect Of Xuezhikang On Carotid Atherosclerosis In Patients With Myocardial Infarction

BackgroundAngiocardiopathy and cerebrovascular diseases are common and multi-onset disease, which have serious effects on the health of human beings, and has been be the first cause of death of human beings, and their pathological basis is atherosclerosis (AS). AS occurs in large and moderate arteries generally, example coronary artery and carotid artery. Recent studies show that there are same causative agents in coronary artery disease and carotid artery disease, and there are compact association between Carotid atherosclerosis and coronary atherosclerosis, their progression are horizontal. Traditionary, the development of AS was thought to be a line procedure, which lipids infiltrated into the intima to sharp plaques, the plaques increased by degrees and put in lumens at last, so the lumens would be narrowed and cause ischemic of the tissue. Therefore, it would result in the occurrence of acute cardiovascular accidents eventually. The occurance of myocardial infarction is based on coronary atherosclerosis, the plaque disrupted and thrombus formation, which caused the coronary occlusion completely.The pathological changes of AS are the lipids deposit in the arteries, which the most are cholesteryl esters. Now humans are focusing on the mechanisms of how to decrease the cholesterol levels and influence atherosclerotic plaques through drug therapies, long-term (beyond one years) effect of statins, not only decrease the levels of lipids, but also slow down or prevent the development of atherosclerosis, even fade away and reverse the atherosclerosis plaque which had come into being..Xuezhikang (XZK) is extracted from red rice which belongs to the traditional Chinese medicine, its main component is lovastatin, and include 13 kinds of natural compound statins and some kinds of unsaturated fatty acid and amino acids. Xuezhikang (XZK) has the effect of improve the lipids metabolism and the function of endothelium. However, it should be investigated penetrating that whether long-term treatment of XZK can benefit to stabilize and fade away the atherosclerotic plaques, and few report was publiced about the effect of XZK on carotid atherosclerosis in patients with myocardial infarction. Therefore, the aim of this study is to investigate the possibility and mechanisms of long-term treatment of XZK in stabilizing and fading away the carotid atherosclerotic plagues and the effect of structure and function of carotid in patients with myocardial infarction by the peripheral vessels ultrasound techniques. Objectives1. To research long-term treatment of XZK in decreasing lipids levels in patients with myocardial infarction.2. To investigate the long -term effect of XZK on carotid atherosclerosis in patients with myocardial infarction, and explore the mechanism.3. To investigate the long -term effect of XZK on structure and function of carotid, and explore the mechanism.Methods1. Characters of all subjects: Sixty-five patients with myocardial infarction were randomly divided into two groups. One group was given capsule of XZK 0.6g, two times a day in addition to conventional therapy. While others took the placebo two times a day in addition to conventional therapy. During the period, all patients kept the similar eating habits from the strart, and prohibited the drugs which can affect lipids metabolism. But the drugs which benefit to coronary artery disease, hypertension or others complication can be used. The mean follow-up The mean follow-up period was 5.58±1.05 years(3.5~ 7 years). The arrangement visited every 6 months. In every visit the doctors inquired all patients at length, and guide their life style.2. Laboratory examination: At the beginning of the experiment and after treatment, blood samples were collected for measuring the lipid profile. While liver enzymes and CK were measured too. Every 6 months the lipid profile, liver enzymes and CK were measured at interval.3. Ultrasound examinations: All patients' carotids were examined with high-frequency ultrasound checked before and after treatment. IMT, the index of atherosclerosis plaque, the common carotid artery diameter, the peak velocity in systolic stage(PSV), the end velocity in diastolic stage(EDV), resistence index(RI), pulsatility index (PI), maximal shear rate (SR), stiffness index (SI), cross-sectional compliance (CSC), distensibility coefficient (DC), compliance (COM), volume dilatancy (VD) were all measured.4. Statistic analysis: Continuous variables are reported as mean±deciazione standard (SD) and have been analysed by SPSS 11.5. Continuous variables have been compared using t test, categorical variables by x~2 test. For all analysis, a P value less than 0.05 was considered significant.Results1. Characters of all subjects: Sixty-five patients with myocardial infarction entered the study, but ten patients quit the treatment. In XZK group, one patient feeled nausea after took the capsule, ALT increased in another patient after one month, they quited the test. In control group, two patients feeled nausea after took the capsule, nonfatal myocardial infarction happened in four patients and two patients died. Eventually, fifty-five patients finished the test, thirty took XZK while twenty-five took placebo.There are no significant difference in all base line characters (P>0.05 ) .2. BMI had no significant difference between before and after treatment in two groups (P>0.05) .3. Lipid profile: In XZK group, the total cholesterol (TC), triglycerides (TG) and the low density lipoprotein cholesterol (LDL-C) were decreased, and the high density lipoprotein cholesterol (HDL-C) were increased after treatment (P<0.05); While in control group, lipid profile had no significant difference (P>0.05).4. Ultrasound measurement: (1) Values of IMT and the index of atherosclerosis plaque in XZK group were lower than before treatment or control group (P<0.05). While in control group, lipid profile had no significant difference (P>0.05). (2) Compared with control group, resistence index and pulsatility index were significantly lower and the peak velocity in systolic stage, the end velocity in diastolic stage and maximal shear rate were significantly higher in XZK group (P<0.05). (3) Compared with control group, stiffness index was significantly lower volume dilatancy and distensibility coefficient and were significantly higher in XZK group (P<0.05), there were no significant difference of cross-sectional compliance and compliance in two groups (P>0.05).. Conclusions1. XZK can significantly decrease TC TG and LDL-C significantly, and increaseTC, TG LDL-C.2. Long-term treatment of XZK can slow down or prevent the development of carotid atherosclerosis, fade away and reverse the carotid atherosclerosis plaque, which the main mechanism is adjust the lipid profile, improve the function of endothelium and increase the shear rate.3. Long-term treatment of XZK can improve arterial elasticity.4. High frequency ultrasound imaging technique provides a reliable method in monitoring the change and rupture of plaques. BackgroundCoronary heart disease (CHD) is the hazardest heart disease in the world, which is first reason to be in hospital and to die in the adult now, the rate of morbidity and mortality is increasing. Recent studies show that the patients with CHD are increasing, but also the average cost because of hospitalization is the most in all disease. The pathological basis of CHD is atherosclerosis (AS), the progress of AS, in particular platelet aggregation and arterial thrombosis because of plaque disruption are recognized as critical to the acute coronary event (acute coronary syndrome, sudden coronary death).The secondary prevention of CHD is the one of basic tactics in the prevention and cure of CHD, which the object is reduce the occurance of acute event in patients with CHD, protect the cardiac muscle, increase the rate and quality of exist. At present, there are a lot of large scale clinical trial exterior and interior show that decrease lipid have a benefit to AS, which are recognized as critical to the prevention and cure of CHD. Statins can inhibit the synthesis of cholesterol. Recent studies show that statins can slow down or prevent of atherosclerosis, what's more it can fade away and reverse the atherosclerosis which have existed. Therefore, it is very significant to the secondary prevention of CHD. The large scale clinical trial about statins example of 4S, CARE, LIPID, WOSCOPS, AFC APS/Tex CAPS, HPS, LIPS, Post-CABG, MIRACL, PROSPE show that statins can not only decrease TC, TG, LDL-C and increase HDL-Csignificantly, but also do a benefit to the primary prevention and secondary prevention of CHD.Xuezhikang(XZK) is extracted from red rice which belongs to the traditional Chinese medicine, its main component is lovastatin, and include 13 kinds of natural compound statins and some kinds of unsaturated fatty acid and amino acids. Xuezhikang (XZK) has the effect of improve the lipids metabolism and the function of endothelium. XZK has been used to the secondary prevention of CHD.Objectives1. To research long-term treatment of XZK in decreasing lipids levels in patients with myocardial infarction.2. To study the secondary prevention effect of Xuezhikang on coronary heart CHD. Methods1. Characters of all subjects: One hundred nineteen patients with myocardial infarction were randomly divided into two groups. One group was given capsule of XZK 0.6g, two times a day in addition to conventional therapy. While others took the placebo two times a day in addition to conventional therapy. During the period, all patients kept the similar eating habits from the strait, and prohibited the drugs which can affect lipids metabolism. But the drugs which benefit to coronary artery disease, hypertension or others complication can be used. The arrangement visited every 6 months. In every visit the doctors inquired all patients at length, and guide their life style.2. Laboratory examination: At the beginning of the experiment and after treatment, blood samples were collected for measuring the lipid profile. While liver enzymes and CK were measured too. Every 6 months the lipid profile, liver enzymes and CK were measured at interval.3. The primary end-points were nonfatal myocardial infarction and deaths from CHD. Total death rate were monitored. 4. Side effects and abnormal laboratory references: Creatine kinase (CK), glutamic pyruvic transaminase (ALT), glutamic oxalacetic transaminase (AST), glutamyl transpeptidase (GGT), creatinine (Cr), urea nitrogen (BUN), uric acid (UA), bilinxbinic acid (TBIL), analysis of blood cell were monitored. Whether the occurrence of myopathic, rhabdomyolysis, myoglobinuria, abnormal ALT, AST and CK were observed.5. Statistic analysis: Continuous variables are reported as mean ± deciazione standard (SD) and have been analysed by SPSS 10.0. Continuous variables have been compared using t test, categorical variables by x~2 test. For all analysis, a P value less than 0.05 was considered significant.Results1. Characters of all subjects: The patients with myocardial infarction entered the study, there are no significant difference in all base line characters (P>0.05). The study is closed on December 31,2004. The mean follow-up period was 4 years, and the longest subject is 7 years.2. Lipid profile: In XZK group, the total cholesterol (TC), triglycerides (TG) and the low density lipoprotein cholesterol (LDL-C) were decreased, and the high density lipoprotein cholesterol (HDL-C) were increased after treatment (P<0.05); While in control group, lipid profile had no significant difference (P>0.05).3. There were 20 patients happened nonfatal myocardial infarction and deaths from CHD, and 21 patients died. The incidence of the primary end-points and the total mortality in XZK group were 4.42% (n=3) and 6.67% (n=4), compared with 18.64% (n=11) and 20.34% (n=12) in the control group. There were significant difference between the two group (P<0.05).4. Side effects and abnormal laboratory references: In XZK group, two patients feeled nausea after took the capsule, ALT and AST increased in two patients after one month, but not beyond three doubles of the normal, CK increased in another patients while not beyond five doubles of the normal. In control group, two patients feeled nausea after took the capsule, ALT increased in one patient after one month, but not beyond three doubles of the normal, CK increased in another patients while not beyond five doubles of the normal. Myopathic, rhabdomyolysis, myoglobinuria were not observed, and there were no significant differences in side effects and abnormal laboratory reference between groups.Conclusion1. XZK can significantly decrease TC TG and LDL-C significantly, and increase TC TG, LDL-C.2. Compares to placebo, Xuezhikang can significantly decrease the incidence of nonfatal myocardial infarction or deaths from CHD. It can also reduce the total mortality. It show that XZK do a benefit to patients with CHD.3. It is safe for the most patients with CHD in China to long-term treatment of XZK...