The prognostic value of pre-procedural plasma C-reactive protein in patients undergoing elective coronary angioplasty.

AIMS: The acute phase reactant C-reactive protein is an important prognostic risk factor in patients with both stable and unstable coronary artery disease. The potential prognostic implications of an abnormal pre-procedural C-reactive protein concentration in patients undergoing elective coronary angioplasty may be relevant for subsequent treatment. METHODS AND RESULTS: Pre-procedural plasma levels of C-reactive protein were measured in 501 patients with stable coronary artery disease undergoing elective coronary angioplasty. The incidence of death or myocardial infarction during a 2-year follow-up was 10.6% (24/227) in patients with an increased C-reactive protein level (>3 mg. l(-1)) and 2.9% (8/274) in patients with a normal C-reactive protein level (RR 3.9, 95% CI 1.7-8.9). Survival without death, myocardial infarction, urgent revascularization or hospital admission for unstable angina was significantly lower in patients with an increased C-reactive protein vs patients with a normal C-reactive protein (log-rank 14.62, P<0.0001). Logistic regression analysis identified an increased C-reactive protein level as a strong independent predictor of event-free survival (RR 2.54, 95% CI: 1.44-4.47, P=0.001). CONCLUSION: Pre-procedural C-reactive protein levels are increased in 45% of patients undergoing elective coronary angioplasty. An increased C-reactive protein level is a powerful independent prognostic indicator for subsequent cardiac events, suggesting that late clinical outcome is markedly influenced by pre-procedural systemic activation of inflammation.     

Proteinuria is a key determinant of death in patients with diabetes after isolated coronary artery bypass grafting

BACKGROUND: Proteinuria is a marker for underlying diabetic nephropathy and may be a surrogate marker for advanced atherosclerosis. It is unknown if proteinuria is a determinant of death in patients with diabetes after coronary artery bypass grafting. We hypothesized that diabetic patients with evidence of proteinuria would have increased mortality and clinical event rates after isolated coronary artery bypass grafting compared with nonproteinuric diabetic patients. METHODS AND RESULTS: We performed an observational of study of 905 diabetic patients with urinalysis and available follow-up data (nonproteinuria, n = 651; proteinuria, n = 254) after isolated coronary artery bypass grafting at the Cleveland Clinic Foundation between January 1989 and December 1992. The proteinuria group was further prospectively stratified into low-concentration (n = 225) and high-concentration (n = 29) groups. The end points of this study were all-cause mortality and the composite end point of death, nonfatal myocardial infarction, and need for repeat revascularization. The mean follow-up time was 66 months. The 5-year mortality rate for the nonproteinuria and proteinuria groups was 20.2% and 29.1% (P <.001), respectively. The 5-year rate of death, nonfatal myocardial infarction, and need for repeat revascularization for the nonproteinuria and proteinuria groups was 25.2% and 36.2% (P <.001), respectively. Significant multivariate predictors of 5-year mortality included age, not using a left internal mammary artery graft to the left anterior descending coronary artery, proteinuria, lower body weight, and increased creatinine level. CONCLUSIONS: Among diabetic patients, proteinuria appears to be an important predictor of death after isolated coronary artery bypass grafting.     

Six-month outcomes of percutaneous coronary balloon angioplasty in acute coronary syndromes: Results from the PURSUIT trial

BACKGROUND: Potent inhibition of the platelet glycoprotein IIb/IIIa receptor has improved the acute outcome of patients presenting with acute coronary syndromes (ACS). For patients with ACS undergoing percutaneous balloon angioplasty without coronary stenting in the era of platelet glycoprotein IIb/IIIa blockade, the long-term prognosis is less clear. OBJECTIVE: To examine the six-month outcome of patients who received eptifibatide within a randomized clinical trial and subsequently underwent balloon angioplasty. METHODS: Patients included in this substudy were enrolled in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial, a randomized study evaluating the efficacy of eptifibatide in reducing the incidence of death or nonfatal myocardial infarction (MI) in non-ST segment elevation ACS. During the index hospitalization, 1151 (12.2%) of the PURSUIT patients underwent percutaneous balloon angioplasty without coronary stenting. RESULTS: Eptifibatide was associated with a significant reduction in the adjudicated composite end point of death or MI at six months after randomization in patients undergoing percutaneous transluminal coronary angioplasty (PTCA) (P=0.037). A trend toward a beneficial effect was evident before the procedure (4.7% versus 6.9%; P=0.13) and at 30 days (12.1% versus 15.3%; P=0.12). The incidence of repeat revascularization was relatively low for patients undergoing PTCA, with no difference observed between the eptifibatide and placebo groups (16.3% versus 14.8%; P=0.51). CONCLUSIONS: Eptifibatide was associated with a sustained beneficial effect to six months in patients with ACS undergoing PTCA. It reduced the incidence of preprocedural MI. The rate of repeat revascularization at six months was low and was not significantly altered by eptifibatide.     

老年多支血管病变患者置入药物洗脱支架与冠状动脉旁路移植术后近远期临床结果

目的:本研究旨在比较老年(年龄≥75岁)稳定性冠心病合并多支血管病变患者行经皮冠状动脉介入治疗(PCI)置入药物洗脱支架(DES)与冠状动脉旁路移植术(CABG)的近远期临床结果。方法:本研究于2003年7月至2006年12月,连续入选年龄≥75岁稳定性冠心病合并多支血管病变患者363例,在我院行PCI置入DES(n=269)或CABG(n=94)治疗。主要终点为24个月时主要不良心脑血管事件(MACCE),次要终点为24个月时全因死亡及非致死性心肌梗死(MI)、脑血管事件和再次血运重建以及全因死亡、非致死性MI和脑血管事件复合终点事件。结果:住院期间,CABG组的病死率(7.4%vs.1.9%,P=0.023)和非致死性MI的发生率(3.2%vs.0,P=0.023),明显高于DES组,CABG组的MACCE的发生率也明显高于DES组(10.6%vs.1.9%,P=0.001)。多因素回归分析结果显示:24个月时,CABG组和DES组的主要终点事件的风险未见明显差异[22.3%vs.15.2%,风险比(HR)=1.62,95%CI 0.63～3.31,P=0.379],两组的全因死亡、心源性死亡、非致死性MI、脑血管事件和再次血运重建的风险也没有明显差异;CABG组全因死亡、非致死性MI和脑血管事件复合终点事件的风险明显高于DES组(19.1%vs.8.2%,HR 3.87,95%CI:1.24～12.37,P=0.009)。结论:本研究提示,与DES相比,CABG可能会增加75岁以上多支血管病变患者的远期全因死亡、非致死性MI和脑血管事件复合终点事件的风险,而未降低再次血运重建和MACCE。     

Outcomes of noncardiac surgery after coronary bypass surgery or coronary angioplasty in the Bypass Angioplasty Revascularization Investigation (BARI)

PURPOSE: Previous studies have shown that coronary artery bypass surgery reduces the risk of cardiac complications after noncardiac surgery. Whether coronary angioplasty provides equivalent protection is not known. SUBJECTS AND METHODS: Patients were randomly assigned to undergo cardiac artery bypass surgery or angioplasty as part of the Bypass Angioplasty Revascularization Investigation trial. All subsequent noncardiac surgeries during a mean (+/- SD) follow-up of 7.7 years were recorded among participants in the ancillary Study of Economics and Quality of Life. Rates of mortality and nonfatal myocardial infarction, length of stay, and hospital costs were compared by the original randomized assignment. RESULTS: A total of 501 patients had noncardiac surgery at a median of 29 months after their most recent coronary revascularization procedure. Mortality and nonfatal myocardial infarction within 30 days of the first noncardiac surgery occurred in 4 of the 250 of the surgery-assigned patients and in 4 of the 251 of the angioplasty-assigned patients (P = 1.0). There were no significant differences in the mean length of hospital stay (6.3 +/- 6.7 versus 6.2 +/- 6.8 days; P = 0.47) or hospital cost ($8,920 +/- $11,511 versus $7,785 +/- $7,643; P = 0.33) between the surgery and angioplasty groups. Similar results were obtained when subsequent noncardiac procedures were included in the analysis. CONCLUSION: Rates of myocardial infarction and death after noncardiac surgery are similarly low after contemporary bypass surgery or angioplasty in patients with multivessel coronary artery disease.     

Pravastatin prevents clinical events in revascularized patients with average cholesterol concentrations. Cholesterol and Recurrent Events CARE Investigators.

OBJECTIVES: This analysis was carried out to determine if revascularized patients derive benefit from the 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor pravastatin. BACKGROUND: The HMG-CoA reductase inhibitors result in substantial reductions in serum cholesterol and stabilization of atherosclerotic plaques in patients with coronary artery disease. METHODS: Pravastatin was found to reduce clinical cardiovascular events in the Cholesterol and Recurrent Events (CARE) trial consisting of 4,159 patients with a documented myocardial infarction and an average cholesterol level (mean 209 mg/dl and all <240 mg/dl). A total of 2,245 patients underwent coronary revascularization before randomization including 1,154 patients with percutaneous transluminal coronary angioplasty (PTCA) alone, 876 patients with coronary artery bypass graft (CABG) alone, and 215 patients with both procedures. Clinical events in revascularized patients were compared between patients on placebo and on pravastatin. RESULTS: In the 2,245 patients who had undergone revascularization, the primary endpoint of coronary heart disease death or nonfatal myocardial infarction (MI) was reduced by 4.1% with pravastatin (relative risk [RR] reduction 36%, 95% confidence interval [CI] 17 to 51, p = 0.001). Fatal or nonfatal MI was reduced by 3.3% (RR reduction 39%, 95% CI 16 to 55, p = 0.002), postrandomization repeat revascularization was reduced by 2.6% (RR reduction 18%, 95% CI 1 to 33, p = 0.068) and stroke was reduced by 1.5% (RR reduction 39%, 95% CI 3 to 62, p = 0.037) with pravastatin. Pravastatin was beneficial in both the 1,154 PTCA patients and in the 1,091 CABG patients who had undergone revascularization before randomization. CONCLUSIONS: Pravastatin reduced clinical events in revascularized postinfarction patients with average cholesterol levels. This therapy was well tolerated and its use should be considered in most patients following coronary revascularization.     

Comparison of long-term (seven year) outcomes among patients undergoing percutaneous coronary revascularization with versus without stenting

Coronary stents have markedly improved the short- and intermediate-term safety and efficacy of percutaneous coronary intervention by improving acute gains in luminal dimensions, decreasing abrupt vessel occlusion, and decreasing restenosis, yet the long-term benefit of coronary stenting remains uncertain. We examined long-term clinical outcomes of death, myocardial infarction, and repeat target vessel revascularization (TVR) among patients enrolled in the Duke Database for Cardiovascular Disease who underwent revascularization with percutaneous transluminal coronary angioplasty alone or stent placement from 1990 to 2002. Among 6,956 patients who underwent percutaneous revascularization, propensity modeling was applied to identify 1,288 matched patients with a similar likelihood to receive coronary stents according to clinical, angiographic, and demographic characteristics. Significant (p <0.05) predictors of stent placement included multivessel disease, diabetes, hypertension, recent myocardial infarction, decreased ejection fraction, and year of study entry. At a median follow-up of 7 years, although treatment with coronary stenting was associated with a significant and sustained decrease in repeat TVR (18.0% vs 28.1%, p = 0.0002) and the occurrence of death, myocardial infarction or TVR (39.2% vs 45.8%, p = 0.004), long-term survival did not significantly differ between treatment groups (19.9% vs 20.5%, p = 0.72). Outcomes of death and myocardial infarction did not significantly differ between patients who did and did not undergo repeat TVR. In conclusion, compared with angioplasty alone, revascularization with coronary stents provides a significant early and sustained decrease in the need for repeat revascularization, but stents do not influence long-term survival.     

纤维蛋白原与高敏C反应蛋白对稳定性冠心病患者心血管事件的预测价值

目的探讨高水平的纤维蛋白原（fibrinogen,FG）和高敏C反应蛋白（hs—CRP）对稳定性冠心病患者心血管事件的预测价值。方法对185例经冠状动脉造影检查证实的稳定性冠心病患者（2002年1月至11月入院患者）分别按FG、hs—CRP水平分组,随访3年,评估发生心血管事件（猝死、心肌梗死、慢性心力衰竭及其他心血管事件）。结果在3年的随访中,发生非致死性心血管事件21例和心血管原因导致的死亡10例。在调整了血脂、体重指数、吸烟、高血压等因素后,FG〉4．0g／L组与FG≤4．0g／L组比较,发生心血管事件的相对危险度为1．97,95％可信区间（CI）为1．68—2．40。hs—CRP〉3．0mg／L组与hs—CRP≤3．0mg／L比较,经调整后发生心血管事件的相对危险度为2．32,95％CI为1．76—2．89。FG〉4．0g／L伴hs—CRP〉3．0mg／L者与FG≤4．0g／L且hs—CRP≤3．0mg／L者比较,发生心血管事件的相对危险度为3．84（P〈0．05）,95％CI为2．80—4．99。结论FG和hs—CRP不仅均为冠心病患者心血管事件重要的独立预测因子,且FG联合hs—CRP检测可增加对冠心病患者心血管事件的预测价值。     

Coronary angioplasty: a therapeutic option for symptomatic patients with two and three vessel coronary disease

Coronary angioplasty is a widely applied revascularization procedure for patients with multivessel coronary artery disease. However, follow-up in this patient subgroup is relatively limited. From 1983 to 1986, coronary angioplasty was performed in 349 and 121 patients with, respectively, two- and three-vessel coronary disease with a primary success rate of 83 and 88%. The in-hospital mortality rate was 2.8% (13 of 470 patients). Complete revascularization was achieved in 128 patients. Among the 397 patients with a successful outcome, 373 (94%) were followed up greater than or equal to 1 year; 79% were free of death, nonfatal myocardial infarction or the need for coronary bypass grafting, and 82% of patients had symptomatic improvement by at least one angina functional class. A second coronary angioplasty procedure was required in 13% of patients. After a mean follow-up period of 27 months, an increased incidence of coronary bypass grafting was noted in patients with incomplete versus complete revascularization (16 versus 7%, p less than 0.05). Among the 222 patients who had repeat cardiac catheterization performed an average of 7 months after angioplasty, 103 were symptomatic; 50% of the 222 patients had at least one vessel with greater than or equal to 50% restenosis and 14% of patients had multiple restenoses. In conclusion, coronary angioplasty can be performed with a high initial success rate and marked symptomatic improvement in patients with multivessel coronary disease. However, in this group's experience, the majority of patients selected for coronary angioplasty with multivessel coronary disease will have incomplete revascularization that can be predicted in the majority of patients before the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of thrombolytic therapy and primary coronary angioplasty with liberal stenting for inferior myocardial infarction with precordial ST-segment depression: Immediate and long-term results of a randomized study

Objectives. The aim of the study was to compare randomly assigned primary angioplasty and accelerated recombinant tissue plasminogen activator (rt-PA), in patients with “high-risk” inferior acute myocardial infarction (ST-segment elevation in the inferior leads and ST-segment depression in the precordial leads).Background. The ST-segment depression in the precordial leads is a marker of severe prognosis in patients with inferior myocardial infarction. The comparative outcome of treatment with primary angioplasty or lysis with accelerated rt-PA has not been investigated.Methods. One hundred and ten patients within 6 h of symptoms were randomized to either treatment. To assess the in-hospital and 1-year outcome of both treatments the following results were compared: death or nonfatal infarction, recurrence of angina, left ventricular ejection fraction (LVEF), and the need for repeat target vessel revascularization (TVR).Results. In patients treated with angioplasty (55) and rt-PA (55) the rate of in-hospital mortality and reinfarction was 3.6% versus 9.1% (p= 0.4). Recurrence of angina was 1.8% versus 20% (p = 0.002), new TVR was used in 3.6% versus 29.1% (p = 0.0003), and the LVEF (%) at discharge was 55.2 ± 9.5 versus 48.2 ± 9.9 (p = 0.0001). There were no hemorrhagic strokes, no emergency coronary artery bypass graft (CABG) and identical (5.5%) need for blood transfusions. At 1 year, the incidence of death, reinfarction or repeat TVR was 11% in the percutaneous transluminal coronary angioplasty (PTCA) group versus 52.7% in the rt-PA group (log-rank 22.38, p < 0.0001).Conclusions. Primary angioplasty is superior to accelerated rt-PA in terms of both myocardial preservation and reduction of in-hospital complications in patients with inferior myocardial infarction and precordial ST-segment depression. Primary angioplasty also yields a better long-term event-free survival.     

Is a strategy of intended incomplete percutaneous transluminal coronary angioplasty revascularization acceptable in nondiabetic patients who are candidates for coronary artery bypass graft surgery? The Bypass Angioplasty Revascularization Investigation (BARI).

OBJECTIVES: Our objective was to determine whether a strategy of intended incomplete percutaneous transluminal coronary angioplasty revascularization (IR) compromises long-term patient outcome. BACKGROUND: Complete angioplasty revascularization (CR) is often not planned nor attempted in patients with multivessel coronary disease, and the extent to which this influences outcome is unclear. METHODS: Before randomization, in the Bypass Angioplasty Revascularization Investigation, all angiograms were assessed for intended CR or IR via angioplasty. Outcomes were compared among patients with IR intended if assigned to angioplasty, randomized to coronary artery bypass graft surgery (CABG) versus angioplasty; and within angioplasty patients only, among patients with IR versus CR intended. RESULTS: At 5 years, there was a trend for higher overall (88.6% vs. 84.0%) and cardiac survival (94.5% vs. 92.1%) in CABG versus angioplasty patients with IR intended. The excess mortality in angioplasty patients occurred solely in diabetic subjects; overall and cardiac survival were similar among nondiabetic CABG and angioplasty patients. Freedom from myocardial infarction (MI) at 5 years was higher in nondiabetic CABG versus angioplasty patients (92.4% vs. 85.2%, p = 0.02), vet was similar to the rate observed (85%) in nondiabetic CABG and angioplasty patients with CR intended. Five-year rates of death, cardiac death, repeat revascularization and angina were similar in all angioplasty patients with IR versus CR intended. However, a trend for greater freedom from subsequent CABG was seen in CR patients (70.3% vs. 64.0%, p = 0.08). CONCLUSIONS: Intended incomplete angioplasty revascularization in nondiabetic patients with multivessel disease who are candidates for both angioplasty and CABG does not compromise long-term survival; however, subsequent need for CABG may be increased with this strategy. Whether the risk of long-term MI is also increased remains uncertain.     

Prospective validity of measuring angina severity with Canadian Cardiovascular Society class: The ACRE study

BACKGROUND: Although the prevalence of angina remains high, the importance of grading angina severity is unclear. OBJECTIVES: To determine the extent to which angina severity is associated with angiographic findings, and the rate of revascularization, mortality and nonfatal myocardial infarction. METHODS: Prospective, population-based study with a 2.5-year follow-up of 2849 consecutive patients with angina undergoing coronary angiography at Barts and the London NHS Trust, London, United Kingdom, in the Appropriateness of Coronary Revascularisation (ACRE) study. Angina severity was assessed with the Canadian Cardiovascular Society (CCS) classification, ranging from class I (mild) to IV (severe). Outcome measures were revascularization rates, and all-cause mortality and nonfatal myocardial infarction. RESULTS: In age-adjusted analyses, a higher CCS class was linearly associated (P<0.001) with a higher number of diseased vessels and impaired left ventricular function. When adjusting for age, sex, smoking, history of hypertension, diabetes, number of diseased vessels, left ventricular function, use of acetylsalicylic acid, beta-blockers or statins, and revascularization status (for death and nonfatal myocardial infarction), a higher CCS class was linearly associated with higher coronary angioplasty (P<0.001) and bypass graft (P=0.03) rates, and lower all-cause mortality and nonfatal myocardial infarction (P<0.001; CCS IV versus I: hazard ratio 2.44, 95% CI 1.46 to 4.09). CONCLUSION: CCS class was linearly associated with angiographic findings, revascularization rates, mortality and nonfatal myocardial infarction. These findings support the importance of a four-level grading of symptom severity among angina patients.     

Association between C-reactive protein levels and subsequent cardiac events among patients with stable angina treated with coronary artery stenting

PURPOSE: To investigate the prognostic value of elevated C-reactive protein levels in patients with stable angina who underwent coronary stenting. METHODS: We followed a consecutive series of 1152 patients with stable angina who had undergone coronary stenting. We measured baseline C-reactive protein levels before stenting with a high-sensitivity assay; 651 patients (57%) had elevated C-reactive protein levels (>5 mg/L). The primary endpoint was either death or myocardial infarction within 1 year after the procedure. Angiographic restenosis was defined as a > or =50% diameter stenosis at follow-up angiography. RESULTS: During the 1-year follow-up, 62 (9.5%) of the 651 patients with an elevated C-reactive protein level and 24 (4.8%) of the 501 patients with normal levels died or had a myocardial infarction (P = 0.002). In a multivariate analysis, elevated baseline C-reactive protein levels were associated with almost a twofold increase in the rate of death or myocardial infarction after coronary stenting (hazard ratio = 1.8; 95% confidence interval: 1.1 to 2.9). Most of the difference in the event rates developed within the first 30 days. Baseline C-reactive protein levels did not correlate with restenosis. CONCLUSION: Elevated preprocedural C-reactive protein levels are associated with a less favorable prognosis in patients with stable angina who undergo coronary stenting. The measurement of C-reactive protein levels in these patients may help to identify those who may benefit from a treatment strategy aimed at the attenuation of inflammation.     

中高危非ST段抬高急性冠状动脉综合征早期侵入与早期保守策略的评价

目的　了解早期侵入与早期保守策略对中高危非ST段抬高急性冠状动脉综合征(ACS)患者住院主要不良心脏事件(MACE)发生情况的影响。方法　根据入院后冠状动脉造影(CAG)与否和时间(≤48h与>48h)对910例中高危非ST段抬高ACS患者分为早期侵入策略组(n=237)和早期保守策略(n=673)两组,分析早期策略与血管重建方式对住院MACE(包括死亡、新发心肌梗死和靶血管再次血管重建)的关系。结果　早期侵入与早期保守组的住院病死率和靶血管血管重建率相当,早期侵入组的住院时间较短,住院MACE(6. 3%比2 .5%,OR0 .384, 95% CI0 188~0 .781,P=0 .006)与新发心肌梗死(4. 6%比0 .9%,OR0 .185, 95% CI0 068~0 .505,P=0.001)的发生率更高。早期侵入组MACE与新发心肌梗死的增加可能与其血管重建操作较多( 86 .9%比67. 5%,P<0 .001)有关。亚组分析显示,早期侵入组与早期保守组中接受经皮冠状动脉介入治疗(PCI)的患者新发心肌梗死、靶血管再次血管重建(TVR)和MACE发生率均相当,无1例死亡;而早期侵入组中接受冠状动脉旁路移植术(CABG)的患者新发心肌梗死的发生率高于早期保守组中接受CABG的患者(7 .5%比1 .8%,P=0 .027)。结论　中高危非ST段抬高ACS患者采取早期侵入策略不增加住院病死率,但有可能增加住院心肌梗死。早期PCI安全可行     

Long-term follow-up of a randomized study of primary stenting versus angioplasty in acute myocardial infarction

PURPOSE: Primary stenting leads to better short-term outcomes than does balloon angioplasty among patients with acute myocardial infarction, but there are no data available on long-term follow-up. SUBJECTS AND METHODS: We designed a randomized study with long-term follow-up to compare primary angioplasty with angioplasty accompanied by implantation of a silicon carbide-coated stent in patients within 24 hours after the onset of acute myocardial infarction. All 88 patients had lesions that were suitable for coronary stenting. RESULTS: There were 44 patients in each of the randomization groups. During long-term follow-up (mean +/- SD: 710+/-282 days), primary stenting was associated with a reduction in the combined endpoint of death, reinfarction, or target vessel revascularization (10 [23%] versus 19 [43%], P = 0.03); death (4 [9%] versus 8 [18%], P = 0.18); reinfarction (1 [2%] versus 4 [9%], P = 0.18); and target lesion revascularization (7 [16%] versus 15 [34%], P = 0.04). Rehospitalization due to ischemic events (unstable angina or reinfarction) was also less frequent in the stent group (6 [14%] versus 10 [23%], P = 0.20). CONCLUSION: Primary stenting in acute myocardial infarction is significantly superior to angioplasty alone in both short-term and long-term follow-up.     

Serum hepatocyte growth factor levels predict long-term clinical outcome after percutaneous coronary revascularization.

AIMS: To evaluate, in patients referred for elective percutaneous coronary revascularization (PCR) without heparin pre-treatment, the relationship between baseline serum levels of the angiogenic growth factors, vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), and clinical outcome. METHODS AND RESULTS: In 488 consecutive patients undergoing elective coronary angioplasty, hsC-reactive protein, HGF, and VEGF levels were measured before heparin administration. The primary endpoint, a composite of death and myocardial infarction, occurred in 44 patients at a median follow-up of 14.9 months. At baseline, VEGF levels were related to C-reactive protein levels and inversely related to age; HGF levels were related to C-reactive protein levels, diabetes, and recent clinical instability. In the univariate analysis, HGF had a significant positive relationship (P=0.003) with the primary endpoint. A similar trend was observed for VEGF (P=0.11). The only three variables significantly associated with the primary endpoint in the multivariable Cox model were HGF (P=0.004), C-reactive protein (P=0.007), and diabetes (P=0.04). CONCLUSION: Our results demonstrate that in patients, without heparin pre-treatment, referred for PCR, a high serum level of HGF is an independent predictor of clinical events during follow-up and is correlated with other surrogate measures of the activity of atherosclerosis.     

Impact of "off-label" utilization of drug-eluting stents on clinical outcomes in patients undergoing percutaneous coronary intervention

The utilization of drug-eluting stents (DES) in "real world" practice has deviated from Food and Drug Administration-approved indications. Safety concerns have arisen from recent reports that suggested increased mortality and nonfatal myocardial infarction (MI) with DES usage. Little is known about the clinical outcomes of patients undergoing intracoronary DES implantation for unapproved indications as a group compared with outcomes after bare metal stent (BMS) placement. The clinical outcomes of 546 patients undergoing DES implantation for >or=1 non-Food and Drug Administration-approved ("off label") indication since the approval of the device were assessed. The group was then matched by propensity score with 546 patients receiving BMSs prior to DES approval for the same indications. The primary endpoint was major adverse cardiac events (cardiac death, nonfatal Q-wave myocardial infarction [MI], and target vessel revascularization) at 12 months. Baseline clinical and angiographic characteristics were well matched between BMS and DES groups. The use of debulking devices was higher in the BMS group. Patients in the BMS group were more likely to be treated with larger diameter and shorter stents. There was no significant difference in the rate of in-hospital and 30-day adverse cardiac events. At 12 months, the primary endpoint of major adverse cardiac events was significantly reduced in the DES group (23.6% vs 16.7%, p=0.004), driven by reductions in the need for repeat revascularization (target lesion revascularization: 16.4% vs 7.8%, p<0.001; target vessel revascularization: 20.2% vs 13.1%, p=0.003). There was no significant difference in freedom from cardiac death or nonfatal Q-wave MI between groups (p=0.27). In conclusion, the utilization of DES for non-Food and Drug Administration-approved indications proved to be efficacious and safe when compared with a BMS cohort matched by propensity score. The advantage for DES was driven by reductions in repeat revascularization. "Off-label" DES use was not associated with increased rates of cardiac death and nonfatal MI at 12 months.     

C677T polymorphism of the methylenetetrahydrofolate reductase gene is a risk factor of adverse events after coronary revascularization

BACKGROUND: A common point mutation (C677T) in the gene for 5,10-methylenetetrahydrofolate reductase (MTHFR) is associated with hyperhomocysteinemia, an independent risk factor and a strong predictor of mortality in patients with coronary artery disease (CAD). The aim of this study was to investigate whether C677T polymorphism can be a predictor of major adverse cardiac events after myocardial revascularization. METHODS: We determined MTHFR genotype in 159 patients with CAD undergoing myocardial revascularization [72 percutaneous transluminal coronary angioplasty (PTCA) and 87 coronary artery bypass graft (CABG)]. Recurrent angina, nonfatal myocardial infarction (MI), target vessel revascularization, heart failure and cardiac death were considered major adverse cardiac events that occurred after discharge from index hospitalization. RESULTS: During the follow-up (6.9+/-0.3 months, mean+/-S.E.M.), the composite endpoint accounted for 25.9%, 11.4% and 4.3% for TT, CT and CC genotype (log-rank statistic 5.2, p=0.02), respectively. Subjects with mutant TT genotype had a threefold increase of any cardiac event (hazard ratio [HR]=3.0; 95% [CI], 1.1-8.1). In multiple-variable regression Cox, predictors of events were TT genotype (HR=2.8; 95% CI, 1.01-7.62, p=0.047), low-ejection fraction<40% (HR=4.5; 95% CI, 1.62-12.6, p=0.004) and revascularization procedure (HR=6.1; 95% CI, 1.86-20.34, p=0.003). CONCLUSIONS: These data indicate that the TT genotype seems to be significantly associated with major adverse cardiac events after myocardial revascularization in CAD patients, suggesting a potential pathological influence of homocysteine in the clinical outcome.     

Clopidogrel is associated with better in-hospital and 30-day outcomes than ticlopidine after coronary stenting

BACKGROUND: Recent reports of fatal ticlopidine-induced blood dyscrasias have led many interventional cardiologists to administer clopidogrel instead of ticlopidine for coronary stenting. Most studies have demonstrated similar outcomes and a more favourable safety profile supporting this change in practice patterns. OBJECTIVES: To assess the clinical outcomes in patients who received clopidogrel rather than ticlopidine after coronary stenting. METHODS: Between June 1996 and December 1998, 652 patients received a clopidogrel-based periprocedural regimen (300 mg loading dose followed by 75 mg daily in addition to acetylsalicylic acid 325 mg daily) and 1717 patients received a ticlopidine-based regimen (500 mg loading dose followed by 250 mg bid in addition to acetylsalicylic acid 325 mg daily). In-hospital and 30-day outcomes were assessed in the two groups. RESULTS: At 30 days, unadjusted mortality was 0.3% in the clopidogrel group versus 1.5% in the ticlopidine group, and myocardial infarction (MI) was also reduced in the clopidogrel group (4.0% versus 6.5%). No difference was found in the rate of repeat revascularization (1.4% versus 1.2%). The combination of death/MI/repeat revascularization at 30 days was reduced by 32%, an absolute difference of 2.9% (6.2% versus 9.1%). On multivariate analysis, clopidogrel was found to be an independent predictor of freedom from nonfatal MI (odds ratio [OR] 0.64, 95% CI 0.41 to 0.99, P=0.04), the composite of death or MI (OR 0.62, 95% CI 0.40 to 0.95, P=0.03) and the composite of death/MI/revascularization (OR 0.69, 95% CI 0.48 to 1.00, P=0.05). CONCLUSION: After coronary stenting, in a large, nonrandomized, consecutive patient experience, clopidogrel appears to be associated with more favourable clinical outcomes than ticlopidine, without increasing the risk of bleeding or peripheral vascular complications.     

Risk stratification in non-ST elevation acute coronary syndromes: predictive power of troponin I, C-reactive protein, fibrinogen and homocysteine

INTRODUCTION: In acute coronary syndromes, myocardial damage markers and acute-phase reactants predict adverse cardiac events. The aim of this study was to define the fitted prognostic value of the most widely used variables of necrosis and inflammation as well as of homocysteine. METHODS AND RESULTS: Troponin I, high-sensitivity C-reactive protein, fibrinogen and homocysteine were measured in 515 consecutive patients admitted to our institution for non-ST elevation acute coronary syndrome. The risk for major events (death or nonfatal myocardial infarction) through 6 months of follow-up was analysed. In the univariate analysis, all markers were related to major events (p<0.01 in all cases). In a multivariate model fitting for baseline characteristics and electrocardiographic changes, the only biomarkers related to major events were C-reactive protein >11 mg/l (2.1 [1.2-3.8] p=0.007) and troponin I >3 ng/ml (1.9 [1.1-3.4] p=0.03). Moreover, the rate of major events was significantly higher (p<0.0001) only when both C-reactive protein and troponin I were increased (31.4% vs. 9.3% if any or both markers were normal). CONCLUSION: In non-ST elevation acute coronary syndromes elevated levels of troponin I, C-reactive protein, fibrinogen and homocysteine are strongly related to the risk of major events. The prognostic value of troponin I and C-reactive protein is independent and additive with respect to each other.