Long-Term Clinical Outcome Of Patients With Acute Coronary Syndrome After Percutaneous Coronary Intervention Treated With Chinese Herbs For Supplementing Qi And Activating Blood Circulation

Part1Long-Term Clinical Outcome of Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention Treated with Chinese Herbs for Supplementing Qi and Activating Blood CirculationObjective:To investigate the long-term clinical outcome of patients with acute coronary syndrome after percutaneous coronary intervention (PCI) treated with Chinese herbs for supplementing qi and activating blood circulation (SQABC), and analyze the relative factors which affect the prognosis of patients with ACS after PCI.Methods:The present study was based on the clinical study of "Combination of Chinese Herbal Medicines and Standard Treatment versus Standard Treatment Alone on Acute Coronary Syndrome after Percutaneous Coronary Intervention". The former study is a multicenter, randomized parallel controlled clinical trial with one-year clinical follow-up. In our study,702ACS patients who were hospitalized in8Beijing and Shanghai hospitals from July2008to September2009were enrolled The control group received standard therapy according to the guideline of Western medicine, the treatment group received standard therapy in combination with Chinese herbs of SQABC (Xinyue Capsule and Fufang Chuanxiong Capsule), with351patients in each group. Telephone and clinic follow-up was performed to recognize the main adverse cardiac events (MACEs) in the last three months in2011. The MACEs consisted of primary end point, secondary end point and combined end point. The primary end point was the composite of cardiac death, nonfatal recurrent myocardial infarction or repeat revascularization (PCI and CABG). The secondary end point was the composite of readmission for acute coronary syndrome, nonfatal cerebrovascular diseases, congestive heart failure, or other thrombus diseases (restenosis and lower extremity arterial occlusion). Combined end point consisted of primary and secondary end point. The relative factors which affected the prognostic outcome of ACS were analyzed using Cox proportional hazards model. Using end point events as outcome variable and events occurring time as time variable. The possible factors which would affect the prognostic were applied in the model to analyze the relative factors and their influence degree on ACS after PCI.Results:621(88.59%) patients accomplished the follow-up,80(11.41%) were lost (41cases in treatment group vs.39cases in control group), the average follow-up time was35.4±3.8months.20(5.70%) cases occurred primary end point in treatment group vs.38(10.86%) in control group. Compared with control group, the primary end point occurring risk of the treatment group was0.53fold [RR,0.53;95%CI (0.30to0.88); P=0.013] and occurring rate decreased5.20%[ARR,-0.052;95%CI (-0.06to-0.01)] in treatment group.21(5.98%) cases occurred secondary end point in treatment group vs.36(10.28%) in control group. Compared with control group, the secondary end point occurring risk of treatment group was0.58fold [RR,0.58;95%CI (0.33to0.97); P=0.037] and occurring rate decreased4.30%[ARR,-0.043;95%CI (-0.06to-0.01)] in treatment group.41(11.68%) cases occurred combined end point in treatment group vs.74(21.14%) in control group. Compared with control group, the combined end point occurring risk of treatment group was0.55fold [RR,0.55;95%CI (0.36to0.76); P=0.001] and occurring rate decreased9.46%[ARR,-0.095;95%CI (-0.11to-0.03)] in treatment group.The relative factors affecting prognostic clinical outcome were analyzed using Cox proportional hazards model. The results showed that the intervention negatively correlated with the primary end point (B=-0.69, P=0.014). Involving vessels amount negatively correlated with the primary end point (B=-0.79, P=0.024). Enrolling Life quality score negatively correlated with the primary end point (B=-1.35, P=0.026). Intervention negatively correlated with the secondary end point (B=-0.54, P=0.049). Intervention negatively correlated with the combined end point (B=-0.66, P=0.001). Left ventricular end diastole diameter positively correlated with the combined end point (B=0.04, P=0.038). Enrolling life quality score negatively con-elated with the combined end point (B=-1.44, P=0.002). The history of hypertensive disease positively correlated with the combined end point (B=0.45, P=0.034). The history of hyperlipemia disease positively correlated with the combined end point (B=0.55, P=0.007).Conclusion:The application of Chinese herbs of SQABC in combination with Western medicine standard therapy can significantly reduce the occurrence of cardiovascular adverse events and improve the long term prognostic outcome. Hypertension, hyperlipemia, low life quality score, increased left ventricular end diastole diameter are the independent risk factors affecting the occurrence of cardiovascular adverse events in ACS after PCI.Part2Effect of Chinese Herbs for Supplementing Qi and Activating Blood Circulation on Ventricular Remodeling of Rats with Acute Myocardial InfarctionObjective:To investigate the effect of Chinese herbs for SQABC on prophase ventricular remodeling (VR) after acute myocardial infarction (AMI) in rats and explore the possible mechanism on extracellular matrix (ECM) metabolism.Methods:The AMI model was established by ligating the left anterior descending coronary artery of rats to induce myocardial infarction.90Wistar rats with model establishment were randomly divided into6groups,15rats in eachgroup. They were sham group (the suture was penetrated around the left anterior descending coronary artery, but not tied), model group, western medicine (WM) group of which Valsartan was administered, supplementing qi (SQ) group of which Panas quinquefolium saponin was given, activating blood circulation (ABC) group of which red peony root saponin was given, supplementing qi and nourishing yin (SQABC) group of which both Panas quinquefolium saponin and red peony root saponin were given. All of the medicine were given by gavage, both sham group and model group were administered of equivalent distilled water. After continuous intragastric administration of4weeks, ultrasonic cardiography was used to examine the morphologic change and heart function. HE staining was used to observe the myocardial pathological change. Serum levels of B-type natriuretic peptide (BNP), cardiac troponin T (cTnT), inflammation factors of tumor necrosis factor-alpha (TNF-a), interleukin-1β (IL-1β), myocardial fibrosis factors laminin (LN), hexadecenoic acid (HA), type III procollagen (PIIINP) were tested by radioimmunoassay method. Myocardium contents of angiotensin II (Ang II), aldosterone (ALD) and tissue growth factor-β1(TGF-β1) were tested by radioimmunoassay method. The protein expression of collagen I, collagen III, matrix metalloproteinases-9(MMP-9), tissue inhibitor of metalloproteinases-1(TIMP-1), osteopontin (OPN) and tenascin-C (TN-C) in myocardial tissue were tested semiquantitatively by immunohistochemical method.Results:After4weeks, compared with model group:(1) Myocardial pathological changes of inflammatory infiltration in cardiac myocyte, edema in cardiac muscle fiber interspace and necrosis in myocardial fibrocyte obviously attenuated in SQABC group.(2) ultrasonic cardiography detection showed that in WM group, ABC group, and SQABC group left ventricular end-systole dimension reduced significantly (P<0.05), while left ventricular ejection fraction increased significantly (P<0.05). Both interventricular septum end-diastole thickness and interventricular septum end-systole thickness increased significantly in SQABC group (P<0.05). The serum level of myocardial damage marker BNP obviously deceased in SQABC group (P<0.05).(3) Serum levels of inflammation factors of TNF-α, IL-β decreased significantly in WM group, ABC group and SQABC group (P<0.05, P<0.01).(4) Myocardial tissue contents of Ang II, ALD and TGF-β1decreased significantly in each administration group (P＜0.05, P＜0.01).(5) Serum levels of myocardial fibrosis factors LN, HA, PIIINP decreased significantly in WM group, ABC group, and SQABC group (P<0.05).(6) The myocardium protein expression of collagen I and collagen III decreased significantly in WM group and SQABC group (P<0.05, P＜0.01).(7) The myocardium protein expression of OPN、TN-C decreased significantly in ABC group and SQABC group (P<0.05, P<0.01).(8)The myocardium protein expression of MMP-9decreased significantly (P＜0.01), TIMP-1increased significantly (P＜0.05), and the ratio of MMP-9/TIMP-1decreased significantly (P＜0.01) in ABC group and SQABC group.Conclusion:(1) Chinese herbs of SQABC can improve the heart function by attenuating the prophase VR of rats after AMI. The possible mechanism of the improvement is that SQABC can inhibit the inflammation reaction, attenuate the activation of neuroendocrine factors and regulate the ECM metabolism.(2) Chinese herbs of SQABC can inhibit prophase VR and improve heart function significantly by regulating the important protein expression of collagen metabolism, MMPS, OPN, and TN-C which influence the ECM structure.