Final results of the STent versus directional coronary Atherectomy Randomized Trial (START)
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OBJECTIVES: This study was designed to compare primary stenting with optimal directional coronary atherectomy (DCA). BACKGROUND: No previous prospective randomized trial comparing stenting and DCA has been performed. METHODS: One hundred and twenty-two lesions suitable for both Palmaz-Schatz stenting and DCA were randomly assigned to stent (62 lesions) or DCA (60 lesions) arm. Single or multiple stents were implanted with high-pressure dilation in the stent arm. Aggressive debulking using intravascular ultrasound (IVUS) was performed in the DCA arm. Serial quantitative angiography and IVUS were performed preprocedure, postprocedure and at six months. The primary end point was restenosis, defined as > or =50% diameter stenosis at six months. Clinical event rates at one year were also assessed. RESULTS: Baseline characteristics were similar. Procedural success was achieved in all lesions. Although the postprocedural lumen diameter was similar (2.79 vs. 2.90 mm, stent vs. DCA), the follow-up lumen diameter was significantly smaller (1.89 vs. 2.18 mm; p = 0.023) in the stent arm. The IVUS revealed that intimal proliferation was significantly larger in the stent arm than in the DCA arm (3.1 vs. 1.1 mm ; p < 0.0001), which accounted for the significantly smaller follow-up lumen area of the stent arm (5.3 vs. 7.0 mm2; p = 0.030). Restenosis was significantly lower (32.8% vs. 15.8%; p = 0.032), and target vessel failure at one year tended to be lower in the DCA arm (33.9% vs. 18.3%; p = 0.056). CONCLUSIONS: These results suggest that aggressive DCA may provide superior angiographic and clinical outcomes to primary stenting. (+info)
Expression of the angiogenic protein, platelet-derived endothelial cell growth factor, in coronary atherosclerotic plaques: In vivo correlation of lesional microvessel density and constrictive vascular remodeling.
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Recent information indicates that platelet-derived endothelial cell growth factor (PD-ECGF), a 45-kDa angiogenic protein, is expressed in the endothelium of various tissues and that its level of expression is correlated with the number of microvessels in human tumors. Because the formation of neovessels is also thought to play a role in atherosclerotic vascular remodeling, we analyzed PD-ECGF expression in fresh, coronary plaque tissues obtained by directional coronary atherectomy. Specimens from 31 patients were collected and analyzed by reverse transcription-polymerase chain reaction, histochemical staining, immunohistochemistry, and in situ hybridization with the use of PD-ECGF-specific primers and probes. Lesional vascular remodeling was assessed by intravascular ultrasound. PD-ECGF immunoreactivity and mRNA were found in plaque macrophages, endothelial cells of plaque neovessels, and stellate smooth muscle cells of 20 atherectomy specimens (64.5%). PD-ECGF immunoreactivity was correlated with the number of lesional microvessels and mast cells. Double-staining experiments revealed a close spatial proximity of PD-ECGF-positive cells and mast cells. Furthermore, the numbers of microvessels and mast cells were significantly higher in lesions lacking compensatory enlargement. The data indicate that PD-ECGF is expressed within cells of the atherosclerotic plaque and may be involved in driving angiogenesis in concert with mast cells. (+info)
Complement and atherogenesis: binding of CRP to degraded, nonoxidized LDL enhances complement activation.
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Complement activation occurs in temporal correlation with the subendothelial deposition of LDL during early atherogenesis, and complement also plays a pathogenetic role in promoting lesion progression. Two lesion components have been identified that may be responsible for complement activation. First, enzymatic degradation of LDL generates a derivative that can spontaneously activate complement, and enzymatically degraded LDL (E-LDL) has been detected in the lesions. Second, C-reactive protein (CRP) colocalizes with complement C5b-9, as evidenced by immunohistological studies of early atherosclerotic lesions, so the possibility exists that this acute phase protein also fulfills a complement-activating function. Here, we report that addition of LDL and CRP to human serum did not result in significant C3 turnover. Addition of E-LDL provoked complement activation, which was markedly enhanced by CRP. Binding of CRP to E-LDL was demonstrated by sucrose flotation experiments. Binding was Ca(2+)-dependent and inhibitable by phosphorylcholine, and the complement-activating property of E-LDL was destroyed by treatment with phospholipase C. These results indicated that CRP binds to phosphorylcholine groups that become exposed in enzymatically degraded LDL particles. Immunohistological studies complemented these findings in showing that CRP colocalizes with E-LDL in early human atherosclerotic lesions. Thus enzymatic, nonoxidative modification of tissue-deposited LDL can be expected to confer CRP-binding capacity onto the molecule. The ensuing enhancement of complement activation may be relevant to the development and progression of the atherosclerotic lesion. (+info)
Systemic inflammatory parameters in patients with atherosclerosis of the coronary and peripheral arteries.
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Plasma concentration of markers of inflammation are increased in patients with atherosclerosis. However, it is unclear whether the pattern and magnitude of this increase vary with the site and extent of disease. In 147 patients undergoing semiquantitative coronary angiography, we measured the acute-phase reactants C-reactive protein (CRP) or serum amyloid A (SAA); the proinflammatory cytokine interleukin 6 (IL-6); the active and total fractions of the anti-inflammatory cytokine transforming growth factor-beta (TGF-beta); the macrophage activation marker neopterin; and the infection marker procalcitonin. Compared with 62 patients without either coronary artery disease (CAD) or peripheral artery disease (PAD), 57 patients with CAD but no PAD showed greater median CRP (0. 4 versus 0.2 mg/dL, P=0.004) and IL-6 (3.8 versus 1.6 pg/mL, P=0. 007) levels and a lower level of active-TGF-beta (57 versus 100 ng/mL, P=0.038). Moreover, CRP, IL-6, and neopterin levels showed a positive and the active TGF-beta level a negative correlation with the extent of coronary atherosclerosis. Compared with these 57 patients with CAD alone, 15 patients with PAD and CAD had higher median levels of SAA (17 versus 7 mg/mL, P=0.008), IL-6 (12 versus 4 pg/mL, P=0.002), neopterin (14 versus 11 mg/dL, P=0.006), and total TGF-beta (11834 versus 6417 ng/L, P=0.001). However, these strong univariate associations of markers of inflammation and atherosclerosis were lost in multivariate analysis once age, sex, and high density lipoprotein cholesterol or fibrinogen were taken into account. Increased plasma levels of CRP, SAA, IL-6, TGF-beta, neopterin, and procalcitonin constitute an inflammatory signature of advanced atherosclerosis and are correlated with the extent of disease but do not provide discriminatory diagnostic power over and above established risk factors. (+info)
Glycoprotein IIIa Pl(A) polymorphism associates with progression of coronary artery disease and with myocardial infarction in an autopsy series of middle-aged men who died suddenly.
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Glycoprotein IIIa (GPIIIa) has a key role in the aggregation of thrombocytes, and it also mediates intimal hyperplasia after endothelial injuries; the possible association of the Pl(A1/A2) polymorphism of the gene for GPIIIa with coronary thrombosis and with the progression of coronary artery disease (CAD) is still to be confirmed. Therefore, the association of the Pl(A) polymorphism with the development of coronary atherosclerosis, coronary narrowing, and myocardial infarction (MI) was studied in a prospective, consecutive autopsy series of 300 middle-aged, white Finnish men (33 to 69 years) suffering sudden out-of-hospital or violent death. Coronary atherosclerosis was measured morphometrically and the coronary stenosis percentage determined from a cast rubber model of the coronary tree. We found a significant inverse relation (P=0.01) between the Pl(A2)-positive genotype and coronary artery stenosis. The frequency of possessing the Pl(A2) allele was significantly (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.22 to 0.98) lower among men with >50% coronary stenosis (18.3%) than among those with <25% stenosis (32.9%). Although the Pl(A) polymorphism was not directly associated with MI, the Pl(A2) allele was present in 11 of the 22 men (50%) with MI and coronary thrombosis (OR 6.6, 95% CI 2.1 to 22.8) but in only 6 of the 47 (12.8%) with MI associated with severe stenosis in the absence of thrombosis. In line with this result, men possessing the Pl(A2) allele also had a larger area of fissured and ulcerated complicated lesions in their coronary arteries (P<0.05). The present results suggest that the Pl(A) polymorphism is involved in the development of CAD and MI. Men with the Pl(A2) allele may harbor more thin-walled, vulnerable coronary plaques, plaques prone to rupture, leading to massive, fatal thrombosis. In contrast, men homozygous for the Pl(A1) allele may more often show stable plaques and present with infarction caused by progressive coronary stenosis. (+info)
Diagnosis and treatment of concomitant aortic and coronary disease: a retrospective study and brief review.
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Coronary arteriosclerosis seriously complicates the surgical treatment of aortic diseases. The aim of our retrospective study was to determine the incidence of coronary artery disease among our surgical patients in treatment for aortic dissection or aneurysm, and to determine whether coronary intervention before aortic surgery appears to affect outcomes. Between 1 January 1993 and 1 March 1998, our center treated 253 patients for aortic dissection or aneurysm. We examined these cases retrospectively for information on diagnostic and treatment methods, both for the aortic lesions and for concomitant coronary arteriosclerosis. Aortic dissection had been detected in 86 (33.9%) patients and aortic aneurysm in 167 (66.1%). Coronary angiography was performed to search for concomitant coronary artery disease in 29 (33.8%) patients with dissection and in 112 (67.1%) patients with aneurysm; of these, 11 (12. 7%) and 54 (32.3%), respectively, were found to have coronary disease. Among 43 patients with abdominal aortic aneurysm in whom coronary angiography was performed, concomitant coronary disease was detected in 36 (83.7%). Coronary artery bypass surgery was performed in 10 patients who had dissection and in 30 patients who had aneurysm; percutaneous transluminal coronary angioplasty was performed in 7 patients who had aneurysm. Perioperative mortality rates in the dissection and aneurysm groups, overall, were 23.2% and 13.8%, respectively Unfortunately, the prospective, random clinical study that would be necessary to prove the case for or against preoperative coronary angiography among subsets of patients in need of aortic repair would raise ethical questions, given the strength of the information already in our possession, gathered by less formal methods. Our study reinforces existing evidence that preoperative angiography can reduce mortality and morbidity in the elective repair of aortic aneurysm, especially thoracic or abdominal aneurysm. However, angiography should not be performed routinely in cases of aortic dissection and should be withheld in cases of type A dissection. (+info)
Impairment of G-protein-mediated signal transduction in the porcine coronary endothelium during rejection after heart transplantation.
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BACKGROUND: Endothelial dysfunction is an early event leading to atherosclerosis. It also occurs after orthotopic heart transplantation and can be used to predict the development of intimal hyperplasia in the coronary artery wall. The present study was designed to assess the time course and specific alterations underlying endothelial dysfunction due to rejection after heart transplantation. METHODS: A porcine model of heterotopic heart transplantation was used. Preoperative serum typing for the class I antigen of the swine lymphocyte alloantigen was performed to ensure compatibility for this antigen. This permitted survival of the graft with a low grade rejection without immunosuppression. Rings (with or without endothelium) of epicardial coronary arteries of native and transplanted hearts were studied in organ chambers filled with modified Krebs-Ringer bicarbonate solution and compared 1, 30 and 60 days after transplantation. RESULTS: Myocardial contractility was normal in all grafts studied at 60 days after transplantation and all coronary arteries were patent. Myocardial biopsies showed the progression of rejection from day 1 to day 60 after implantation. All endothelium-dependent relaxations were normal one day after transplantation. Endothelium-dependent relaxations to serotonin and to the alpha 2-adrenergic agonist UK14304 (which both activate receptors coupled to Gi-proteins) and to sodium fluoride (a direct activator of G-proteins) were decreased 30 days after transplantation, while those to the calcium ionophore, A23187, and bradykinin were shifted to the right and those to ADP were normal. At 60 days, endothelium-dependent relaxations mediated by the Gi-protein pathway were decreased further while the concentration-relaxation curves to the other agonists were further shifted to the right. Endothelium-independent relaxations to the nitric oxide donor, Sin-1, were progressively reduced at 30 and 60 days, but maximal relaxations were maintained at 60 days. Histomorphometric studies showed a progressive increase in the percentage of coronary rings with intimal thickening from day 1 to day 60 after transplantation. CONCLUSIONS: The progressive endothelial dysfunction reported in this model of accelerated coronary atherosclerosis after transplantation without immunosuppression involves preferentially the pertussis-toxin-sensitive Gi-protein-mediated pathway. Endothelium-independent relaxations are decreased at 60 days, as are all other endothelium-dependent relaxations. Decreased endothelium-dependent vasodilatation may contribute to the development of coronary graft vasculopathy. (+info)
In vitro analysis of coronary atheromatous lesions by intravascular ultrasound; reproducibility and histological correlation of lesion morphology.
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AIM: To determine the reproducibility and histological correlation of qualitative intravascular ultrasound imaging of atheromatous coronary arteries using the recently proposed European Society of Cardiology classification of plaque composition in conditions approximating the clinical setting. METHODS: Atheromatous lesions (n=21), identified from 30 post-mortem human coronary arteries, were imaged using intravascular ultrasound in a pulsatile flow system which simulates coronary flow. Fifty sites (21 x minimum lumen area and 29 x distal reference sites) were selected independently by two observers from continuous video recordings. Atheromatous plaque was classified as echodense, echolucent, heterogeneous or calcified by each observer and by one observer on separate occasions. Arterial specimens were histologically sectioned at these sites and similarly analysed by a third observer blinded to the intravascular ultrasound appearances. RESULTS: Overall inter- and intra-observer reproducibility for plaque-type (Kappa 0.87[0.80-0.94] and 0.89[0. 85-0.93 respectively]) and focal calcification (0.78[0.74-0.82] and 0.88[0.84-0.92]) was high. Differences in site selection significantly influenced reproducibility particularly at reference sites. Agreement for overall plaque type between intravascular ultrasound and histology occurred in 89% of sites (Kappa 0.73[0.69-0. 77]). Specificity and positive predictive values for individual plaque types were greater than 90%. CONCLUSION: Using modern intravascular ultrasound technology in an in vitro system which approximates the clinical setting the proposed ESC classification of plaque composition by intravascular ultrasound is reproducible and correlates well with histology. It should therefore perform reliably in diagnostic intravascular ultrasound examinations and in the guidance of percutaneous coronary interventions. (+info)