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2006 Vol. 3, No. 2

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Six-month results of a biodegradable polymer and rapamycin-coating stent for coronary artery disease
Yuxiao ZHANG, Caiyi LU, Qiao XUE, Peng LIU, Wei VAN, Rui CHEN
2006, 3(2): 67-70.
Objective To assess the safety and efficacy of a novel biodegradable polymer and rapamycin-coating stent, the EXCEL stent, in the treatment of coronary artery disease (CAD), as compared with the Cypher? stent. Methods In this prospective, non-randomized study, 60 consecutive patients with symptomatic CAD received either an EXCEL stent (n=32), or a Cypher? stent(n=28),according to their respective treatment intention. Follow-up angiography was performed at a mean of 180±40 days. The primary endpoint of the study was the occurrence of a major adverse cardiac event (MACE), including death, myocardial infarction, or target-vessel revascularization during the 6 months after stenting. The secondary end points included the in-stent late luminal loss (LLL), percentage of in-stent stenosis of the luminal diameter, and the rate of restenosis (luminal narrowing of 50 percent or more) at 6 months. Results There were no significant differences between the two groups in baseline characteristics, including the distribution of target vessel and lesion types. During the follow up period of 6 months, there were no occurrences of MACE in either group. Twenty-seven patients (84%) in the EXCEL group and 10 (36 %) in the Cypher? group underwent quantitative coronary angiography at 6 months. For these patients, no restenosis occurred, and there were no differences in the in-stent stenosis of the luminal diameter (5.98±5.52 % vs 5.21±6.3%, P>0.05) and the LLL (-0.02±0.09 mm vs -0.01+0.07 mm, P>0.05). Conclusions Compared with the Cypher? stent, the EXCEL Stent with biodegradable polymer and rapamycin-coating showed similar efficacy in the prevention of neointimal proliferation, restenosis, and associated clinical events in CAD patients.
Stent, drug, polymer—enefits, risks, and opportunities
Samuel J. Shubrooks
2006, 3(2): 71-72.
It has been well established that use of drug-eluting stents has resulted in marked reduction in neointimal prolif-eration following stenting and that this is reflected clini-cally in a very significant decrease in late lumen loss, in-stent restenosis, and target lesion revascularization. This benefit occurs, however, in the setting of delayed endothe-lial and vascular wall healing with its potential for continu-ing thrombogenicity requiring more prolonged use of dual antiplatelet therapy to prevent stent thrombosis. Large se-ries of patients receiving sirolimus-eluting and paclitaxel-eluting stents have indicated the absence of any increase in adverse cardiac events up to one year following stenting. Questions have been raised, however, as to whether there may be any late "catch-up" in restenosis or in late stent thrombosis.
Prophylactic endovascular management of peripheral artery disease in elderly candidates prior to cardiac surgery
Gianluca Rigatelli, Massimo Giordan, Loris Roncon, Emiliano Bedendo, Tranquillo Milan, Paolo Cardaioli, Giorgio Rigatelli
2006, 3(2): 73-76.
Background and objectives Peripheral vascular disease (PVD) is a major risk factor in candidates for cardiac surgery and can impact morbidity and mortality in the perioperative and follow-up period. Elderly patients with PVD may benefit from endovascular treatment prior to cardiac surgery. We sought to assess the common clinical settings requiring prophylactic endovascular treatment before coronary surgery in elderly patients, the results, and the mid-term impact on subsequent revascularization. Methods Between November 2002 and June 2006, 37 patients (25 males, mean age 79.9±8.3 years, mean serum creatinine 1.9±0.6 mg/dl) underwent endovascular repair of PVD before cardiac surgery. For each patient, diagnostic methods, indications for intervention, types of interventions, procedural success, and complications were recorded. Results Four clinical settings were identified: renal artery stenting prior to coronary surgery (7 patients), iliac artery angioplasty and stenting (10 patients) in order to facilitate aortic balloon pump insertion after surgery, subclavian artery angioplasty and stenting prior to utilization of ipsilateral arterial conduits bypass surgery (5 patients), and carotid artery stenting before coronary surgery (15 patients). Technical success was achieved in all patients (100%); complications included brachial artery occlusion (1 patient), minor stroke (2 patients), contrast nephropathy (1 patient), and minor bleeding at the puncture site (3 patients). All patients underwent successful coronary or valvular surgery; no patients died in the perioperative period. After a mean follow-up of 26.6±3.1 months, all patients are alive and free from anginal symptoms or valvular dysfunction without clinical or Doppler ultrasonography evidence of restenosis of the implanted peripheral vascular stents. Conclusions It is not unusual for elderly patients who are candidates for cardiac surgery to require endovascular intervention for significant PVD prior to coronary bypass or valvular surgery. The results showed a low complication rate. The cardiologists have a fundamental role, not only in the diagnosis of peripheral vascular stenosis, which was seen frequently in patients with significant CAD, but also in the appropriate endovascular management of these high-risk patients.
Peripheral intervention before bypass surgery in the elderly: feasible and effective, but is it necessary?
Sze-Piaw CHIN, Kui-Hian SIM
2006, 3(2): 77-77.
Rigatelli and colleagues tackled the issue of concomitant non-coronary atherosclerosis among elderly patients undergoing car-diac surgery.1 Ilio-femoral disease, renal artery stenosis, carotid stenosis, and even disease of supra-aortic vessels may variously impact the patient's recovery from surgery. Also, the fact that in-volvement of two or more arterial beds are more common among the elderly makes this article all the more relevant at this time.
C-reactive protein as a predictor for cardiac events in Chinese elderly patients with coronary heart disease
Guangyong HUANG, Caiyi LU, Xingli WU, Yuxiao ZHANG, Guangyong HUANG
2006, 3(2): 78-81.
Background and objective To assess the predictive value of C-reactive protein(CRP) for major adverse cardiac events and the association between CRP level and the coronary lesion morphology and extent in patients with coronary heart disease (CHD). Methods CRP was measured on admission in 177 consecutive elderly (age>60 years) patients with CHD who underwent coronary angiography. Patients were divided into high CRP group (CRP>3mg/L) and normal CRP group (CRP <3mg/L). The association between CRP levels and the coronary lesion features, including severity of stenosis (mild, moderate, severe), extent of lesion (diffused or non-diffused), eccentricity of the plaque (eccentric or non-eccentric) were analyzed. Patients were followed up for a mean of 8 months for the occurrences of major adverse cardiac events (MACE). Results Compared with patients in normal CRP group, patients in high CRP group were more frequently to have unstable angina, multi-vessel, diffuse, eccentric lesions, positive remodeling, and non-smooth plaques (P<0.01). Kaplan-Meier analysis showed patients in high CRP group had a significantly lower MACE-free survival rate than patients in normal CRP group (Log-rank =12.0, /"<().01); Cox regression analysis indicated CRP level as an independent predictor for the occurrence of MACE (OR=3.16, P<0.05) Conclusions High CRP level is associated with more extend, severe and eccentric coronary lesions and is an independent predictor for MACE in elderly patients with CHD.
Clinical perspective on C-reactive protein in prognostication of major adverse cardiac events in the elderly with established coronary heart disease
Olabode Oladeinde
2006, 3(2): 82-84.
The systemic response to tissue injury, regardless of cause is characterized by a cytokine-mediated alteration in the hepatic synthesis of a number of different plasma proteins, known collectively as 'acute phase reactants'. These proteins include C-reactive protein, serum amyloid A protein, alpha 1 glycoprotein, ceruloplasmin, alpha macroglobulins, comple-ment components (C1-C4, factor B, C9, Cll), alphal antitrypsin, alphal antichymotrypsin, fibrinogen, prothrombin, factor VDI, plasminogen, haptoglobin, ferritin, immunoglobu-lins and lipoproteins. The initiation of the acute phase response is linked to the production of hormone-like polypeptide me-diators now called cytokines, namedly, interleukin l(IL-l), tumor necrosis factor, interferon gamma, interleukin 6 (IL-6), leukemia inhibitory factor, ciliary neurotropic factor, oncostatin M, and interleukin 11 (IL-11).
Skin fold thickness at abdomen: a simple anthropometric measurement may compliment metabolic syndrome definition in patients with normal waist circumference
Toan C Nguyen, Thai Q Ngo, Son V Nguyen, Hieu T Luong, Khoa TA Pham, Cong D Nguyen
2006, 3(2): 85-92.
Backgroud and Objectives Previous studies have reported that skin fold thickness (SF) strongly correlated with insulin resis-tance in the metabolic syndrome (MetS). In this study, we developed a MetS definition by SF at A8 point (SFA8) on Erdheim diagram (MetSSFAS) in essential hypertensive patients. Subjects and Methods Medical records of 268 essential hypertensive patients (126 males and 122 females) were analyzed, including 210 non-diabetic patients (NDM group) and 58 patients with diabetes (DM group). The mean age was 61.4 ± 9.9 and 59.0 ±11.0 years, respectively. The control group consisted of 90 non-diabetic, non-hypertensive patients with a mean age of 58.0 ± 11.3 years. The proposed MetSSFAS definition included SFA8 specific values ( >30 mm in female and >27 mm in male) and at least two of the following: raised triglyceride levels ( >1.7 mmol/L), or specific treatment for this lipid abnormality; raised blood pressure (SBP>130 mmHg and/or DBP>85 mmHg), or treatment of previously diagnosed hypertension; reduced HDL-cholesterol (5.6 mmol/1), or previously diagnosed DM. Metabolic Syndrome by the National Cholesterol Education Program and International Diabetes Federation definitions were determined with abdominal obesity defined by Asia-Pacific criteria for waist circumference (NCEPA and IDFA). Results The percentage of MetS as defined by NCEPA, IDFA and MetSSFAS in NDM group was lower than that of NCEPA, IDFA and MetSSFAS in DM group [OR=7.7 (95%CI, 2.9-20.2) and 2.5 (95%CI, 1.4-4.8) and 2.7 (95%CI, 1.3-5.6), respectively] and higher than that of the control group [OR=53.3 (95%CI, 16.7-170.6), 5.8 (95%CI, 2.6-13.2) and 18.8 (95%CI, 7.3-48.7), respectively]. The percentage of MetS by NCEPA, IDFA and MetSSFAS in males in NDM group was lower than the percentage of MetS by NCEPA, IDFA and MetSSFAS in females in NDM group (50.8% and 77.9%, P< 0.001; 15,9% and 67. 2%, P< 0.001; 60.3% and 73.8%, P <0.05, respectively). In subjects with normal WC or both normal WC and BMI, the percentage of MetS by SFA8 was higher than that the percentage of MetS by NCEPA (36.9% and 50.8%, P< 0.05 and 36.0% and 51.0%, P< 0.05). The sensitivity, specificity, false positive rate, positive predictive value, negative predictive value of MetSSFAS assessed with NCEPA definitions were 0.87, 0.73, 0.27, 0.79 and 0.82, respectively. There was a close agreement between MetSSFAS and NCEPA (The coefficient of Kapa was 0.60, P< 0.001). Conclusions The MetSSFAS definition was developed which may be useful in order to define and manage MetS in patients with normal WC or normal weight.
Obesity and the risk of cardiovascular disease and diabetes mellitus
Matthew J. Sorrentino
2006, 3(2): 93-94.
The increasing prevalence of obesity worldwide has many experts concerned about the worsening health of a large proportion of the population. It is well recognized that obe-sity is associated with a higher mortality, an increased risk of hypertension and hyperlipidemia, cardiovascular disease, dia-betes mellitus, osteoarthritis, gall bladder disease and possibly some cancers. Currently it is estimated that over two thirds of adults in the United States are overweight and nearly one third are clinically obese.' Of special concern is the rapid increase in obesity among children. Other countries both developed and developing are experiencing similar trends.
Apolipoprotein E polymorphism in northern Chinese elderly patients with coronary artery disease
Yangchun ZOU, Xingyuan JIA, Xinchun YANG, Liang CUT, Dayi HU, Xiufang HONG
2006, 3(2): 95-98.
Background and objective Apolipoprotein E is a constituent of lipoproteins with considerable variation due to cysteine-argin-ine exchanges. We investigated the relationship between apo E gene polymorphism and the occurrence of coronary artery disease (CAD) in the older population of northern China. Methods The distribution of the Hhal polymorphisms of the apolipoprotein E gene was determined among 55 patients with CAD (CAD group), which was compared with that of 36 elderly subjects without CAD (control group). Results Genotype distributions at both sites (apo E gene 112-bp and 158-bp sites ) were different between the CAD and control groups. The CAD group had lower apolipoprotein E"el"frequencies than the control group (/><0.05). Conclusion Individu-als with apolipoprotein E"e2"are likely to have a reduced risk of developing coronary artery disease as demonstrated by elderly subjects in Northern China.
Apolipoprotein E and coronary artery disease: the debate is still on
Liang Ge, Thach Nguyen
2006, 3(2): 99-99.
Apolipoprotein E (Apo E) is quite a fascinating lipoprotein. As reported by Zou et al.' in this issue of the Journal of Geriatric Cardiology, Apo E has three isoforms, e2, e3, and e4, differing from each other by the polymorphisms found in the amino acid residues at sites 112 and 158. Apo E and its three isoforms, with e3 being the most common, is like a Pandora's box of sorts, where upon investigation, interesting correlations to some very prominent modern diseases have been found. For example, there was evidence that the presence of one e4 allele in their Apo E gene increased the risk for type-2 Alzheimer's disease and two e4 alleles would increase further this risk. Also intriguing is the subject of this paper by Zou et al.: the relationship between Apo E isoform e2 and the pres-ence of coronary artery disease (CAD).
Insulin induces PKC-dependent proliferation of mesenteric vascular smooth muscle cells from hypertensive patients
Xukai WANG, Yan WANG, Ying WAN, Xianwen JI, Chenming YANG
2006, 3(2): 100-106.
Background and objectives Proliferation of human vascular smooth muscle cells (VSMCs) induced by hyperinsulinemia is a very common clinical pathology. Extensive research has focused on PKC (Protein kinase C)-MAPK (mitogen-activated protein kinase) intracellular signal transduction and the phenotypic modulation accompanied by reorganization of intracellular F-actins in VSMCs. Methods DNA synthesis, signaling of ERK1/2 MAPKs, and changes in a-smooth muscle (SM) actin and F-actin were studied in hypertensive and normotensive human arterial VSMCs exposed to insulin and PMA with and without the PKC inhibitor, GF109203X. Results Differences among cell types in MAPK signaling, cx-SM actin, and F-actin isoforms in VSMCs harvested from the arteries of patients with essential hypertension (EH) and normotension (NT) were identified in response to insulin treatment. Proliferation and activation of MAPK were more pronounced in EH VSMCs than in NEH VSMCs. Insulin exposure decreased expression of a-SM actin and was accompanied by rearrangement of intracellular F-actins in VSMCs, especially in the EH group. These effects were reversed by treatment with the PKC inhibitor. Conclusions Human mesenteric VSMCs of EH and NT patients differed in proliferation, MAPK signaling, and degree of changes in a-SM actin and F-actin isoforms immediately following insulin exposure in vitro.
Effects of antioxidants on homocysteine thiolactone-induced apoptosis in human umbilical vein endothelial cells
Weijun GU, Juming LU, Guoqing YANG, Qinghua GUO, Baoan WANG, Yiming MU, Changyu PAN
2006, 3(2): 107-111.
Background and objectives Hyperhomocysteinemia is an independent risk factor for cardiovascular disease. Homocysteine thiolactone (HcyT), one of the homocysteine metabolites in vivo, is toxic both in vivo and in vitro. The aim of this study was to investigate the effect of HcyT on apoptotic damage in human umbilical vein endothelial cells (HUVECs) and the role of antioxidants in the reduction of HcyT-induced apoptosis. Methods HUVECs were cultured in DMEM supplemented with 20% heat inactivated fetal bovine serum cell cultures were maintained in a humidified 5% CO, atmosphere at 37°C. Cytotoxicity was determined by MTT assay, which consists of hypodiploid cells with propidium iodide labeling and intracellular reactive oxygen species levels using 2',7'-dichlorofluorescein diacetate as the probe by flow cytometry. Results HcyT (250-2000uM) induced HUVECs apoptosis in a time- and concentration-dependent manner. Reactive oxygen species levels rose in response to increasing HcyT concentrations at 24-h incubation. The reduction of cell apoptosis by N-acetylcysteine, vitamin E, or pyrrolidine dithiocarbamate, occurred simultaneously with a signifi-cant decrease in intracellular reactive oxygen species levels. Conclusion HcyT exerts its cytotoxic effects on endothelial cells through an apoptotic mechanism involving cellular reactive oxygen species production. The capacity of N-acetylcysteine, vitamin E, and pyrrolidine dithiocarbamate to scavenge HcyT-induced cellular reactive oxygen species correlates well with their efficiency to protect against HcyT-promoted apoptotic damage. The protective effect of pyrrolidine dithiocarbamate on cell apoptosis indicates HcyT-generated hydrogen peroxide may provoke cell apoptosis via activating nuclear factor-kappa binding protein.
Effect of hepatocyte growth factor on left ventricular remodeling after acute myocardial infarction in canine
Ping LI, Tingshu YANG, Liling LIANG
2006, 3(2): 112-115.
Background and objectives To investigate the effect of hepatocyte growth factor (HGF) on left ventricular (LV) remodeling after acute myocardial infarction (AMI). Methods AMI was produced by ligation of proximal left anterior descending coronary artery (LAD) in 12 mongrel canines. These animals were randomized into 2 groups. In HGF group (n=6), canines were injected with pc-DNA3-HGF 1ml (about 300ug) at the margin of infarcted myocardium; in control group (n=6) canines were injected with equal volume of normal saline. Cardiac function and left ventricular remodeling were evaluated with echocardiography at 1, 4, 8 weeks after MI. LV myocardium specimens were obtained at 8 weeks and stained with hematoxylin and eosin for histological examination or with sirius red to assess the collagen content. Results Compared with control group, LVEF in HGF group was significantly higher at 4 weeks (49.61 + 6.66 vs 39.84+6.39; P<0.05) and at 8 weeks (51.57+8.53 vs 40.61+7.67; P<0.05) after AMI, while LVESV was significantly lower in HGF group than that in control group at 8 weeks after AMI (18.98+3.47 vs 25.66+5.86; P<0.05). Posterior left ventricular wail thickness decreased significantly from 1 wk to 8 wks after AMI in control group, while remained unchanged in HGF group.Compared with control group, histological examination showed more neovascularization and less scar, and sirius red staining indicated higher volume of type III collagen (7.10±4.06% vs 3.77+1.09%; P<0.05) and lower collagen I/III ratio value (1.11 ±0.52 vs 2.94±2.48; P<0.05) in HGF group. Conclusion HGF gene transfer might improve cardiac function and LV remodeling after acute myocardial infarction by stimulating angiogenesis, reducing fibrosis, and reducing myocardial scarring.
Myocardial infarction secondary prevention study (MISPS)
Hongcai SHANG, Guohua DAI, Junhua HANG, YaozuXIANG, YangWANG, Junping ZHANG, Wuxun DU, Jingyuan MAO, Boli ZHANG, Chen YAO, Weiliang WENG, Tiancai WEN
2006, 3(2): 116-119.
Background Traditional Chinese medicine (TCM), especially herbal medicine, has been widely used in China and now is also being increasingly used in other countries for the treatment of cardiovascular diseases. Although many studies have demonstrated that certain Chinese herbal products are effective and safe for the treatment of cardiovascular diseases, most of these lack sufficient quality. Therefore, large randomized clinical trials and further scientific research to determine its safety, effectiveness are necessary. QiShen YiQi Dripping Pills (QSYQDP) is a herbal preparation clinically used in the treatment and prevention of coronary artery disease. Preliminary observations have shown its safety and effectiveness. Methods/Design This randomized, controlled trial will recruit 3600 patients with a history of myocardial infarction. Patients will be randomized into two groups by a Centr-Randomized System. One group receives QSYQDP, the other group receive aspirin. This trial protocol will describe eligibility criteria, detailed information on the treatment definition, blinding, endpoints, statistical methods, sample size determination, data management, legal aspects, and the current status of the trial. Discussion This trial is one of the first randomized, controlled clinical trial to evaluate the efficacy and safety of traditional Chinese herbal medicine in the treatment and secondary prevention of coronary artery disease. The results of this study should help to define the role of TCM in modern medical care, as well as to provide the management strategy for CAD patients in China and other countries.
Evidence based medicine: clinical trials that guide the management of ST-elevation myocardial infarction of elderly patients
Hoang Pham, James Nguyen, Liang Ge, Thach Nguyen
2006, 3(2): 120-127.
Cardiovascular disease is the most frequent diagnosis in elderly people and is the leading cause of death in both men and women older than 65 years. Every year in the United States more than 700,000 patients arrive at the emergency room with ST-segment elevation myocardial infarction (STEMI). About 60 percent of hospital admissions for AMI are of people older than 65 years. Their in-hospital, 1-month, and 1-year mortality is high.l In this article, we will provide a review on clinical trials that guide the management of ST-elevation myocardial infarction of the elderly patients.
Coronary artery imaging using MDCT and MRA
Rajiv Kumar
2006, 3(2): 128-128.
The potential benefits provided by new imaging tech-nologies for the diagnostic evaluation of CAD are quantified by considering the expense, time, and associated risk of pos-sible complications of traditional invasive angiography. Two techniques currently being used in clinical practice are mag-netic resonance angiography (MRA) and computed tomogra-phy angiography (CTA). MRA and CTA are particularly dis-advantaged in comparison to tradition angiography because of their poorer temporal and spatial resolutions. They each posses their own strengths and weaknesses and as the tech-nologies continue to develop the diagnostic accuracy and the clinical value of these tools are further studied. The end goal is to have a fast, non-invasive technique to efficiently screen and diagnose patients with symptoms of CAD.