Preprocedural inflammatory markers do not predict restenosis after successful coronary stenting.

BACKGROUND: Levels of C-reactive protein (CRP), serum amyloid A protein (SAA), and interleukin-6 (IL-6) can predict coronary restenosis following angioplasty and stent deployment in patients with unstable angina. We investigated whether measurement of periprocedural inflammatory markers predicted the angiographic outcome at 6 months in stable angina patients undergoing coronary stenting. METHODS: We prospectively studied 182 patients; 152 patients underwent elective and successful stenting procedure for de novo lesions in native and nongrafted coronary arteries and 30 individuals in the control group underwent diagnostic angiography alone. CRP, SAA, and IL-6 were determined by high-sensitivity immunoassays. RESULTS: At 6 months, quantitative computer-assisted angiographic analysis in 133 patients with stents showed a binary restenosis rate of 33.8%. Statins were being taken by 80% of the patients. There were no significant differences between the pre- or postprocedure values of CRP, SAA, or IL-6 in patients with or without in-stent restenosis. CONCLUSIONS: Preprocedural inflammatory markers in stable angina subjects undergoing coronary artery stent deployment did not correlate with the development of in-stent restenosis. Differences in pathobiology between stable and unstable coronary syndromes, the widespread use of statins with anti-inflammatory activity in our cohort of patients, along with different mechanisms underlying the early angiographic appearances of restenosis as compared to clinical end points, most likely explain our findings.

Automated quantitation of peripheral blood neutrophil activation in patients with myocardial ischaemia.

BACKGROUND: Coronary ischaemic syndromes are associated with neutrophil activation. The Bayer automated haematology analysers can detect increased light scatter of neutrophil populations, which correlates with neutrophil activation. We aimed to assess the role of an automated analyser in detecting systemic neutrophil activation in peripheral blood samples of patients with coronary ischaemia. METHODS: A prospective cross-sectional study was undertaken in 18 patients with chronic stable angina, 9 with unstable angina and 26 normal control subjects. Whole blood samples were taken to assess neutrophil count and light scatter, and serum samples were taken from some patients for assessment of Troponin T, C-reactive protein (CRP) and myeloperoxidase (MPO). In addition, whole blood was stimulated in vitro with interleukin (IL)-8 and N-formyl-methionyl-leucyl-phenylalanine (fMLP) to assess changes in neutrophil light scatter detected by the analyser. RESULTS: Neutrophil light scatter was increased in patients with chronic stable and unstable angina compared to normal control subjects (normal subjects 74.1 (73.3, 75.0) (mean arbitrary units (95% confidence intervals, (CI)) vs. 78.6 (76.9, 80.3) in the chronic stable angina group P<0.001 and 77.1 (75.3, 79.0) in the unstable angina group P<0.007). In vitro stimulation of whole blood produced comparable increases in neutrophil light scatter when morphological changes in neutrophils were demonstrable under electron microscopy. CONCLUSIONS: Automated measurement of neutrophil activation by light scatter is possible using the Advia 120 analyser and is superior to a neutrophil count in discriminating groups with angina. This technique may be useful in monitoring disease activity and progression in coronary artery disease and in guiding the use of anti-inflammatory therapies.

The endothelial nitric oxide synthase (Glu298Asp and -786T>C) gene polymorphisms are associated with coronary in-stent restenosis.

AIMS: Coronary stent deployment is a major advance in percutaneous treatment of ischaemic heart disease, but 10-40% of patients still develop angiographic restenosis by 6 months due to neointimal hyperplasia. Patient-specific factors, including genetic factors, can contribute to this process. We have conducted a prospective study to examine the involvement of genetic risk factors (eNOS, ACE, MMP-3, IL-6, and PECAM-1) in restenosis following coronary stent deployment. METHODS AND RESULTS: A total of 226 patients who underwent elective and successful coronary artery stenting to de novo lesions in native coronary arteries were studied. Two hundred and five (90.7%) patients were restudied by coronary angiogram at 6 months and the stented lesions were assessed using an automated quantitative angiography system. Genotype was determined by polymerase chain reaction (PCR) and restriction enzyme digestion. Restenosis rate, defined as >or=50% diameter stenosis, was 29.3%. The overall genotype frequency distributions were in Hardy-Weinberg equilibrium for all variants. Carriers of the 298Asp allele of the eNOS Glu298Asp polymorphism showed a higher frequency of restenosis with an odds ratio of 1.88 (95%CI: 1.01-3.51, P=0.043) compared to 298Glu homozygotes. Carriers of the -786C allele of the eNOS -786T>C polymorphism also showed a higher frequency of restenosis with odds ratio of 2.06 (95%CI: 1.08-3.94, P=0.028). These effects were essentially additive and were independent of other classical risk factors. Other studied genes did not show significant association with coronary in-stent restenosis. CONCLUSION: In patients with coronary artery disease, the possession of the 298Asp and -786C variants of the eNOS gene are a risk factor for coronary in-stent restenosis, demonstrating the importance of the nitric oxide system in restenosis.

Potassium channel openers in myocardial ischaemia: therapeutic potential of nicorandil.

Potassium channel openers or agonists represent a novel new class of compounds in the treatment of a range of cardiovascular disorders, particularly angina pectoris and hypertension. Nicorandil is the only clinically available potassium channel opener with antianginal effects, and with comparable efficacy and tolerability to existing antianginal therapy. It confers benefits through a dual action: opening the mitochondrial KATP channels leading to preconditioning of the myocardium and a nitrate-like effect. Myocardial preconditioning is important in reducing infarct size, severity of stunning and cardiac arrhythmias. These effects make nicorandil a unique antianginal compound that reduces both pre- and after-load and improves coronary blood flow. Comparative and noncomparative studies support the use of nicorandil as monotherapy or in combination with other antianginal therapy for stable angina pectoris. However, large studies are required to confirm its role in the treatment of acute coronary syndromes despite the favourable results from small studies.

The EUROPA trial: design, baseline demography and status of the substudies.

BACKGROUND: Angiotensin-converting enzyme inhibitors do reduce both mortality and morbidity in patients with left ventricular dysfunction, recent myocardial infarction and hypertension. However, the long-term effects in patients with coronary artery disease have not been established. The EUROPA study is designed to assess the long-term (3-4 years) effects of perindopril on the reduction of cardiac events in patients with proven stable coronary artery disease but with no evidence of heart failure. STUDY DESIGN AND METHODS: EUROPA is a 12236 patient, randomised, double-blind, placebo-controlled and multicentre trial. EUROPA had an initial run-in period of 4 weeks during which patients received 4 and then 8 mg of perindopril daily to assess tolerance to maximum dose. This was followed by a double-blind randomisation to either perindopril or placebo. Patients were followed-up at 3 and 6 months and then 6 monthly until the last patient included in the main study completes the 3-year follow-up. EUROPA includes five sub-studies. Each of these sub-studies investigates the effects of perindopril on a different aspect of coronary artery disease: endothelial dysfunction, atherosclerosis progression regression, diabetes mellitus, inflammation, thrombosis, neurohormonal activation. Patients are characterised genetically to assess characteristics associated with improved or unfavourable outcome. The final results of EUROPA will be available in 2002.

Why is recurrent myocardial ischaemia a predictor of adverse outcome in unstable angina? An observational study of myocardial ischaemia and its relation to coronary anatomy.

OBJECTIVE: To establish why recurrent myocardial ischaemia predicts adverse outcome in patients with refractory unstable angina on maximal medical treatment. DESIGN: Prospective observational study in 101 patients with refractory unstable angina who underwent continuous ST-segment monitoring and kept detailed pain charts prior to cardiac catheterization. Setting Tertiary referral centre. RESULTS: Significant coronary disease was identified in 90 subjects with 74 (82%) having multivessel disease, 41 (46%) complex lesion morphology, and 10 (11%) subjects with definite features of intra-coronary thrombus. The frequency of complex lesions or intra-coronary thrombus did not differ in relation to the extent of coronary disease. Recurrent chest pain was present in 72 of the 90 (80%) subjects, while transient ischaemia was detected in 26 (29%). The presence of transient ischaemia was a powerful predictor of complex lesions or thrombus (odds ratio 7.1;P<0.001). Subjects with severe recurrent chest pain had a greater frequency of intracoronary thrombus (odds ratio 9.5;P<0.05). CONCLUSIONS: In unstable angina once the normal mechanisms causing myocardial ischaemia (i.e. increased myocardial demand and coronary vasoconstriction) have been treated using maximal antianginal treatment, the continued development of transient myocardial ischaemia is strongly associated with complex coronary lesion morphology and intracoronary thrombus. It is already known that patients with complex lesion morphology and intracoronary thrombus have an adverse outcome in unstable angina and therefore it is this association that explains why transient ischaemia is a predictor of poor outcome in unstable angina.