A comparison of angioplasty with medical therapy in the treatment of single-vessel coronary artery disease. Veterans Affairs ACME Investigators.

BACKGROUND. Despite the widespread use of percutaneous transluminal coronary angioplasty (PTCA), only a few prospective trials have assessed its efficacy. We compared the effects of PTCA with those of medical therapy on angina and exercise tolerance in patients with stable single-vessel coronary artery disease. METHODS. Patients with 70 to 99 percent stenosis of one epicardial coronary artery and with exercise-induced myocardial ischemia were randomly assigned either to undergo PTCA or to receive medical therapy and were evaluated monthly. The patients assigned to PTCA were urged to have repeat angioplasty if their symptoms suggested restenosis. After six months, all the patients had repeat exercise testing and coronary angiography. RESULTS. A total of 107 patients were randomly assigned to medical therapy and 105 to PTCA. PTCA was clinically successful in 80 of the 100 patients who actually had the procedure, with an initial reduction in mean percent stenosis from 76 to 36 percent. Two patients in the PTCA group required emergency coronary-artery bypass surgery. By six months after the procedure, 16 patients had had repeat PTCA. Myocardial infarction occurred in five patients assigned to PTCA and in three patients assigned to medical therapy. At six months 64 percent of the patients in the PTCA group (61 of 96) were free of angina, as compared with 46 percent of the medically treated patients (47 of 102; P less than 0.01). The patients in the PTCA group were able to increase their total duration of exercise more than the medical patients (2.1 vs. 0.5 minutes, P less than 0.0001) and were able to exercise longer without angina on treadmill testing (P less than 0.01). CONCLUSIONS. For patients with single-vessel coronary artery disease, PTCA offers earlier and more complete relief of angina than medical therapy and is associated with better performance on the exercise test. However, PTCA initially costs more than medical treatment and is associated with a higher frequency of complications.     

Effect of exercise on coronary endothelial function in patients with coronary artery disease

BACKGROUND: Studies of the cardioprotective effects of exercise training in patients with coronary artery disease have yielded contradictory results. Exercise training has been associated with improvement in myocardial perfusion even in patients who have progression of coronary atherosclerosis. We therefore conducted a prospective study of the effect of exercise training on endothelial function in patients with coronary artery disease. METHODS: We randomly assigned 19 patients with coronary endothelial dysfunction, indicated by abnormal acetylcholine-induced vasoconstriction, to an exercise-training group (10 patients) or a control group (9 patients). To reduce confounding, patients with coronary risk factors that could be influenced by exercise training (such as diabetes, hypertension, hypercholesterolemia, and smoking) were excluded. In an initial study and after four weeks, the changes in vascular diameter in response to the intracoronary infusion of increasing doses of acetylcholine (0.072, 0.72, and 7.2 microg per minute) were assessed. The mean peak flow velocity was measured by Doppler velocimetry, and the diameter of epicardial coronary vessels was measured by quantitative coronary angiography. RESULTS: In the initial study, the two groups had similar vasoconstrictive responses to acetylcholine. After four weeks of exercise training, coronary-artery constriction in response to acetylcholine at a dose of 7.2 microg per minute was reduced by 54 percent (from a mean [+/-SE] decrease in the luminal diameter of 0.41+/-0.05 mm in the initial study to a decrease of 0.19+/-0.07 mm at four weeks; P<0.05 for the comparison with the change in the control group). In the exercise-training group, the increases in mean peak flow velocity in response to 0.072, 0.72, and 7.2 microg of acetylcholine per minute were 12+/-7, 36+/-11, and 78+/-16 percent, respectively, in the initial study. After four weeks of exercise, the increases in response to acetylcholine were 27+/-7, 73+/-19, and 142+/-28 percent (P<0.01 for the comparison with the control group). Coronary blood-flow reserve (the ratio of the mean peak flow velocity after adenosine infusion to the resting velocity) increased by 29 percent after four weeks of exercise (from 2.8+/-0.2 in the initial study to 3.6+/-0.2 after four weeks; P<0.01 for the comparison with the control group). CONCLUSIONS: Exercise training improves endothelium-dependent vasodilatation both in epicardial coronary vessels and in resistance vessels in patients with coronary artery disease.     

Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries

Acetylcholine is believed to dilate normal blood vessels by promoting the release of a vasorelaxant substance from the endothelium (endothelium-derived relaxing factor). By contrast, if the endothelium is removed experimentally, acetylcholine constricts blood vessels. We tested the hypothesis that muscarinic cholinergic vasodilation is impaired in coronary atherosclerosis. Graded concentrations of acetylcholine and, for comparison, the nonendothelial-dependent vasodilator nitroglycerin were infused into the left anterior descending artery of eight patients with advanced coronary stenoses (greater than 50 percent narrowing), four subjects with angiographically normal coronary arteries, and six patients with mild coronary atherosclerosis (less than 20 percent narrowing). Vascular responses were evaluated by quantitative angiography. In several segments each of four normal coronary arteries, acetylcholine caused a dose-dependent dilation from a control diameter of 1.94 +/- 0.16 mm to 2.16 +/- 0.15 mm with the maximal acetylcholine dose (P less than 0.01). In contrast, all eight of the arteries with advanced stenoses showed dose-dependent constriction, from 1.05 +/- 0.05 to 0.32 +/- 0.16 mm at the highest concentration of acetylcholine (P less than 0.01), with temporary occlusion in five. Five of six vessels with minimal disease also constricted in response to acetylcholine. All vessels dilated in response to nitroglycerin, however. We conclude that paradoxical vasoconstriction induced by acetylcholine occurs early as well as late in the course of coronary atherosclerosis. Our preliminary findings suggest that the abnormal vascular response to acetylcholine may represent a defect in endothelial vasodilator function, and may be important in the pathogenesis of coronary vasospasm.     

Therapeutic angiogenesis in ischemic heart disease: gene or recombinant vascular growth factor protein therapy?

In the last decennium the challenge to research has been to find methods of inducing new vascular growth in ischemic myocardium due to atherosclerotic coronary artery disease, which could not be treated with balloon angioplasty or coronary artery by-pass grafting. Therapeutic angiogenesis with recombinant vascular endothelial growth factor proteins or gene encoding for the proteins is a new potential treatment for cardiovascular disease. The greatest interest and research has been concentrated on basic Fibroblast Growth Factor (FGF1 and FGF2) and Vascular Endothelial Growth Factor A (VEGF-A165 and VEGF-A121). Several small clinical phase I-II safety and efficacy trials with recombinant vascular endothelial growth factor proteins or gene encoding for the proteins have demonstrated that these treatment regimes seem to be safe and the results have been encouraging. However, two large doubleblind randomized placebo-controlled studies with intracoronary infusions of the recombinant proteins FGF2 and VEGF-A165 could not detect any clinical effect. Large scaled phase II studies with gene therapy are in progress. Therapeutic angiogenesis is still a promising new treatment in patients with coronary artery disease. However, more research including large scaled clinical trials is needed before deciding whether the vascular endothelial growth factor therapy either as a gene or a recombinant slow-release protein formulation therapy can be offered to patients with severe coronary artery disease, which cannot be treated with conventional revascularization.     

Vascular endothelial growth factor mRNA expression can be a marker for response to antiviral treatment of HCV

Angiogenesis has a significant pathogenic role in liver damage-associated hepatitis C virus infection. We evaluated whether chronic hepatitis C (CHC) is associated with elevated levels of angiogenesis marker (vascular endothelial growth factor) and whether it is modulated by therapy. Vascular endothelial growth factor (VEGF) mRNA was determined in the 36 CHC patients included in this study before therapy and 12 weeks after receiving antiviral combination therapy, pegylated interferon alpha-2b plus ribavirin, compared to 20 healthy controls. CHC patients showed elevated baseline VEGF level before and during treatment, but it was decreased in responder group, indicating a shift toward an “anti-angiogenic” process in CHC patients. In conclusion, this suggests that VEGF mRNA level could be useful as non-invasive, base markers of response to therapy.     

VEGF inhibition and renal thrombotic microangiopathy

The glomerular microvasculature is particularly susceptible to injury in thrombotic microangiopathy, but the mechanisms by which this occurs are unclear. We report the cases of six patients who were treated with bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), in whom glomerular disease characteristic of thrombotic microangiopathy developed. To show that local reduction of VEGF within the kidney is sufficient to trigger the pathogenesis of thrombotic microangiopathy, we used conditional gene targeting to delete VEGF from renal podocytes in adult mice; this resulted in a profound thrombotic glomerular injury. These observations provide evidence that glomerular injury in patients who are treated with bevacizumab is probably due to direct targeting of VEGF by antiangiogenic therapy.     

冠心病患者血浆OLAB、BNP和CRP水平变化分析

检测冠心病患者血浆OLAB、BNP和CRP水平变化, 探讨冠心病发病机制及不稳定性心绞痛(UAP)治疗前后对其影响.用RIA和ELISA法对124例冠心病患者和30名对照者血浆中的OLAB、BNP和CRP水平变化及相关性进行研究, 同时对48例UAP经皮冠状动脉形成术(PTCA)治疗前、后对上述三项指标的变化进行分析; 结果表明冠心病患者与对照组比较BNP水平有显著性差异(P＜0.01),尤其是AMI和UAP组比SAP组升高更明显; CRP水平比对照组明显增高(P＜0.05),特别是不稳定性心绞痛和AMI组升高明显(P＜0.05);AMI组血浆OLAB水平明显高于正常和其他两组, OLAB、BNP和CRP三项在UAP组中治疗前后比较差异显著(P＜0.01).总之,OLAB、BNP和CRP参与了冠心病的发病过程, 并可预测心肌梗死患者远期心功能恢复的情况, UAP组经PTCA支架术后, 三项指标均明显降低, 可作为疗效观察的一个重要参数, OLAB参与了冠状动脉粥样硬化的全过程及AMI的发病始末.     

An analysis of outcome following percutaneous transluminal coronary artery angioplasty. An autopsy series

We analyzed autopsy findings on 26 patients who died following percutaneous transluminal coronary angioplasty (PTCA). Twenty-one patients died within 3 weeks of undergoing PTCA; demonstrable cardiac complications were found in 19 patients: platelet-fibrin thrombi (10 patients [48%]), coronary artery dissections (17 patients [81%]), thromboemboli (13 patients [62%]), atheroemboli (seven patients [33%]), and myocardial infarcts (17 patients [81%]). An increased incidence of coronary platelet-fibrin thrombi was noted when compared with a non-PTCA cardiac autopsy population (five of 53 patients). Apparently there was an increased incidence of coronary atheroemboli and thromboemboli in the patients with coronary platelet-fibrin thrombi (eight patients) when compared with patients who did not have platelet-fibrin thrombi (five patients), although this was not statistically significant. There was no evidence of a systemic hypercoagulable state or of disseminated intravascular coagulation. The pathogenesis of this is unclear; however, vasospasm and a disruption of the endothelial surface induced by PTCA with subsequent platelet activation are possible causes. Although not statistically significant, there was a proponderance of female subjects (seven patients) and an increased incidence of diabetes mellitus (six patients) and hypertension (13 patients) when compared with a control population of all patients undergoing PTCA at The Cleveland (Ohio) Clinic Foundation in 1987, suggesting that diabetes mellitus, hypertension, and female sex may be clinical risk factors for fatal complications following PTCA.     

In situ detection of platelet-derived growth factor-A and -B chain mRNA in human coronary arteries after percutaneous transluminal coronary angioplasty.

Experimental studies have shown that platelet-derived growth factor (PDGF) plays a role in wound-healing processes after angioplasty. In humans, after percutaneous transluminal coronary angioplasty (PTCA), this has not yet been documented. Six coronary arteries of five patients who died after PTCA were studied. The angioplasty sites were sliced serially, and the slices were studied using immunocytochemistry and in situ hybridization. Monoclonal antibodies were directed against muscle actin, vimentin, macrophages, and endothelium. In situ hybridization was performed using a synthetic oligonucleotide probe complementary to the PDGF-A and -B chain mRNAs. The identification of cells was based on a comparison with immune-stained sections. Positive autoradiographic signals for PDGF-A and -B chain mRNAs were found at the site of the PTCA injury and related to areas that contained macrophages, spindle cells, smooth muscle cells, and endothelial cells of neovascularization. In humans, both PDGF-A and -B chain mRNAs are expressed at sites of PTCA injury. The expression relates to the reparative response, and it appears that the cells involved are macrophages, spindle cells, smooth muscle cells, and endothelial cells of neovascularization. This is the first study to document the expression of PDGF-A and -B mRNAs at sites of repair in human coronary arteries after PTCA. It suggests strongly that PDGF is involved in the repair process after PTCA.     

Overcommitment predicts restenosis after coronary angioplasty in cardiac patients

The objective of this study is to examine the role of a particular stress-enhancing psychosocial risk factor, termed overcommitment, in predicting restenosis after successful percutaneous transluminal coronary angioplasty (PTCA). Overcommitment defines a personal pattern of coping with demands characterized by excessive striving in combination with a strong desire of being approved and esteemed. One hundred six consecutive male patients with coronary artery disease who underwent PTCA were followed over a mean of 12 months. The restenosis rate as defined by quantitative angiography was 34%. Multivariate analysis revealed independent effects of high density lipoprotein cholesterol (odds ratio [OR] 3.19), age (OR 3.43), and overcommitment (OR 2.86) on risk of restenosis. In conclusion, a stress-enhancing psychosocial person characteristic termed overcommitment acts as an independent predictor of coronary restenosis after PTCA. As overcommitment is subject to cognitive-behavioral intervention, results have implications for a more comprehensive approach to secondary prevention in cardiac patients. This research was supported by the German Research Foundation (DFG-SFB 242/D18). We thank Dr. Myriam Valk-Draad for her collaboration.     

Peripheral monocytes from diabetic patients with coronary artery disease display increased bFGF and VEGF mRNA expression

Background  

Macrophages can produce vascular endothelial growth factor (VEGF) in response to hypoxia, transforming growth factor β1 (TGF-β1), angiotensin II, basic fibroblast growth factor (bFGF), and interleukin-1. These factors have been found in the serum of coronary artery disease (CAD) patients as well as in atherosclerotic lesions. The aim of the present study was to test the hypothesis that the expression of VEGF, TGF-β1 and bFGF in peripheral monocytes and lymphocytes is related to CAD.     

冠心病的基因治疗

冠心病是严重威胁人类生命和健康的常见疾病。虽然冠状动脉旁路移植术和血管内介入治疗已经得到充分发展，但仍有一部分严重冠心病患者不能得到有效的治疗。近年来，冠心病的基因治疗成为研究的热点。本文从以下几方面对冠心病基因治疗的研究进展进行简要介绍；目的基因的选择，基因载体的选择和心脏基因导入途径的选择。对于血管内皮生长因子基因，成纤维细胞生长因子基因，肝细胞生长因子基因和促血管生成素－1基因在冠心病治疗中应用的实验和研究现状提供了重点介绍。     

Multiresolution wavelet analysis of the body surface ECG before and after angioplasty

Electrocardiographic recordings of patients with coronary artery stenosis, made before and after angioplasty, were analyzed by the multiresolution wavelet transform (MRWT) technique. The MRWT decomposes the signal of interest into its coarse and detail components at successively finer scales. MRWT was carried out on different leads in order to compare the P-QRS-T complex from recordings made before with those made after percutaneous transluminal coronary angioplasty (PTCA). ECG signals before and after successful PTCA procedures show distinctive changes at certain scales, thus helping to identify whether the procedure has been successful. In six patients who underwent right coronary artery PTCA, varying levels of reperfusion were achieved, and the changes in the detail components of ECG were shown to correlate with the successful reperfusion. The detail components at scales 5 and 6, corresponding approximately to the frequencies in the range of 2.3–8.3 Hz, are shown to be the most sensitive to ischemia-reperfusion changes (p<0.05). The same conclusion was reached by synthesizing the post-PTCA signals from pre-PTCA signals with the help of these detail components. For on-line monitoring a vector plot, analogous to vector cardiogram, of the two most sensitive MRWT detail components is proposed. Thus, multiresolution analysis of ECG may be useful as a monitoring and diagnostic tool during angioplasty procedures.     

Pro-Angiogenic Cytokines as Cardiovascular Therapeutics

Coronary artery and peripheral vascular disease are global health concerns with limited therapies. Currently available medical and surgical therapies for these disease processes are highly effective for only a fraction of patients. Extensive effort has been devoted to finding molecular therapies to enhance perfusion and function of ischemic myocardial and peripheral skeletal muscle. Angiogenic cytokines (fibroblast growth factor [FGF], vascular endothelial growth factor [VEGF], hepatocyte growth factor [HGF], placental growth factor, stromal cell-derived factor-1alpha) have shown theoretical and experimental promise in upregulating endogenous endothelial progenitor cell-mediated angiogenesis. Preliminary clinical trials have suggested improvements in myocardial and peripheral perfusion following therapy with FGF, VEGF, and HGF. Further studies on the efficacy of cytokine-mediated angiogenesis are required before widespread clinical application is possible. Investigation into adjunctive cytokine therapies for myocardial and peripheral muscle ischemia is warranted. Based on experimental evidence, appropriate angiogenic cytokine therapy should provide benefits in both perfusion and hemodynamic function.     

The role of balloon angioplasty in the management of coronary artery disease

PTCA is a new technique for the treatment of certain patients with coronary artery disease. It involves dilatation of stenotic segments of artery using a balloon catheter, and is carried out in cardiac catheterization laboratories. If successful, the need for coronary bypass surgery may be removed, although some patients with initially successful PTCA will come to surgery eventually. Successful PTCA is associated with relief of angina, improved angiographic appearances and coronary perfusion. The primary success rate is between 65% and 80%, and the restenosis rate approximately 25%. 80% of patients will be angina free one year after PTCA. In this paper the indications, contraindications, technology, results and complications are discussed.     

Percutaneous transluminal coronary angioplasty in a child with Kawasaki disease.

A successful attempt at percutaneous transluminanl coronary angioplasty (PTCA) to relieve stenosis of the mid-portion of the left anterior descending artery was achieved in a 6-year 9-month old boy who had multiple coronary aneurysms and stenosis due to Kawasaki disease. Despite the progression of coronary stenosis he had been well except for the perfusion defect of the anterior wall of myocardium on 99mTc-MIBI SPECT with dipyridamole infusion until PTCA was carried out after 4-year 4-months of the onset of illness. The area of stenosis was 70% before PTCA and 20% after PTCA. No restenosis at the site of PTCA was observed on follow-up angiography at 26 months after PTCA. This successful attempt may indicate that this procedure should be considered early in subclinical stenosis to prevent ischemic cardiac damage.     

Cognitive adaptation as a predictor of new coronary events after percutaneous transluminal coronary angioplasty.

OBJECTIVE: We tested whether the psychological components of cognitive adaptation theory would predict new coronary events after a first percutaneous transluminal coronary angioplasty (PTCA). METHODS: A consecutive sample of patients treated successfully with PTCA were enrolled in the study. Of 343 patients approached, 303 (88%) agreed to participate and were interviewed shortly before hospital discharge. We measured the components of cognitive adaptation theory (optimism, self-esteem, and mastery) during the interview. Five patients were excluded from the analysis because of early, in-hospital reocclusion. New cardiac events (coronary artery bypass grafting, PTCA, myocardial infarction, or disease progression) were examined within 6 months of the first PTCA. We obtained 6-month follow-up data on 98% of patients. RESULTS: The cognitive adaptation index predicted new cardiac events, even when demographic variables and medical variables thought to predict restenosis were statistically controlled (p = .02). CONCLUSIONS: These results suggest that persons who respond to their illness by perceiving control over their futures, by having positive expectations about their futures, and by holding a positive view of themselves seem to be at less risk for a new cardiac event after a first PTCA.     

巨噬细胞移动抑制因子基因rs1007888位点单核苷酸多态性与哈萨克族 冠状动脉粥样硬化性心脏病发病的相关性

背景：有研究表明巨噬细胞移动抑制因子是具有多种生物活性的细胞因子,在机体的炎症和免疫反应中起重要作用。巨噬细胞移动抑制因子rs1007888已被报道与多种炎症性疾病相关,但其与哈萨克族冠状动脉粥样硬化性心脏(冠心病)病易感性是否具有关联性少见报道。 目的：探讨巨噬细胞移动抑制因子rs1007888位点基因多态性与新疆哈萨克族人群冠心病之间的相关性。 方法：选择2012年6月至2014年4月于新疆医科大学附属第一医院心脏中心入院,经皮冠状动脉造影检查确诊的哈萨克族冠心病患者230例为冠心病组,以同期冠脉造影阴性、排除冠心病诊断的478例哈萨克族为健康对照组。采用实时荧光定量PCR法对所有纳入对象巨噬细胞移动抑制因子rs1007888位点基因多态性进行检测,比较两组间巨噬细胞移动抑制因子基因多态性频率分布的差异。 结果与结论：冠心病组与对照组基因型分布符合Hardy-Weinberg平衡(P > 0.05),两组的巨噬细胞移动抑制因子rs1007888位点基因型、等位基因频率均差异无显著性意义(P > 0.05)。结果证实,rs1007888位点基因多态性与新疆维吾尔自治区哈萨克族冠心病发病无显著相关性,该位点突变可能不是哈萨克族人群冠心病的易感因素。  中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程全文链接：     

Why does diabetes mellitus increase the risk of cardiovascular disease?

The main etiology for mortality and a great percentage of morbidity in patients with diabetes mellitus is atherosclerosis. The pathogenesis of cardiovascular disease (CVD) in diabetes is multifactorial and can be affected by metabolic and other factors. A hypothesis for the initial lesion of atherosclerosis is endothelial dysfunction, defined pragmatically as changes in the concentration of the chemical messengers produced by the endothelial cell and/or by blunting of the nitric oxide-dependent vasodilatory response to acetylcholine or hyperemia. Endothelial dysfunction has been documented in patients with diabetes and in individuals with insulin resistance or at high risk for developing type 2 diabetes. The way endothelial function altered in diabetic patients is not yet fully understood, but the loss of normal endothelial function could be involved in the pathogenesis of diabetic angiopathy, as endothelial dysfunction is associated with diabetic microangiopathy and macroangiopathy. Factors associated with endothelial dysfunction in diabetes include activation of protein kinase C, overexpression of growth factors and/or cytokines, and oxidative stress. Changes in endothelium function may lead to the coronary artery circulation being unable to cope with the increased metabolism of myocardial muscle independently of a reduced coronary artery diameter. Finally, recent reports indicate that an improved metabolic control in diabetic patients, whatever the treatment used, is associated with near normalization or restoration of normal endothelial function.