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C-Reactive Protein and Immunoglobulin-E Response to Coronary Artery Stenting in Patients with Stable Angina

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C-Reactive Protein and Immunoglobulin-E Response to Coronary Artery Stenting in Patients with Stable Angina Clinical Studies C-Reactive Protein and Immunoglobulin-E Response to Coronary Artery Stenting in Patients with Stable Angina Okan ERDOGAN,1 MD, Armagan ALTUN,1 MD, Cetin GUL,1 MD and Gultac OZBAY,1 MD SUMMARY Recent reports indicate that inflammatory mechanisms play a crucial role in the patho- genesis of atherosclerosis and neointimal proliferation as well as coronary restenosis. To provide baseline data for further studies regarding stenting, restenosis and inflammatory response, we prospectively conducted a clinical study to investigate the time related response of plasma levels of immunoglobulin-E (IgE) and C-reactive protein (CRP) which are two different inflammatory markers mediated by different cytokines in stable patients who underwent elective coronary artery stenting. Thirteen consecutive stable patients who underwent coronary artery stenting were included in the study. Levels of IgE and CRP were determined pre- and poststent implantation on four consecutive days and at the end of the first as well as third month. Levels of these two markers were gradually elevated on postprocedure days while reaching peak values on the second and third days for IgE (initial 278 ± 335 IU/mL vs peak 350 ± 489 IU/mL, P = 0.01) and CRP (initial 0.5 ± 0 mg/dL vs peak 2.7 ± 3 mg/dL, P = 0.002), respectively. High levels gradually returned to baseline values determined at the end of the first and even third months after stent implantation implying an acute inflammatory reaction. Stent implantation seems not to cause any persistent and ongoing inflammatory response in the long term. (Jpn Heart J 2003; 44: 593-600) Key words: C-reactive protein, Immunoglobulin E, Inflammation, Atherosclerosis, Stent CORONARY artery stenting is one of the most effective means for the preven- tion of restenosis in atherosclerotic coronary artery segments.1,2) Recent reports indicate that inflammatory mechanisms play a crucial role in the pathogenesis of atherosclerosis and neointimal proliferation as well as coronary restenosis.3,4) C- reactive protein (CRP), an acute phase reactant, increases several fold within 24 to 48 hours after an inflammatory stimulus.5) Additionally, mast cells have also been implicated in the pathogenesis of coronary heart disease.6) Their number in the adventitia of coronary arteries increases with the progression of atherosclero- sis. Higher mast cell counts are seen in coronary arteries containing both fresh From the 1 Department of Cardiology, School of Medicine, Trakya University, Edirne, Turkey. Address for correspondence: Okan Erdogan, MD, Arseven Sitesi Villa Konutlari NO:2, D-100 Karayolu, Edirne, 22030, Turkey. Received for publication November 11, 2002. Revised and accepted January 9, 2003. 593 Jpn Heart J 594 ERDOGAN, ET AL September 2003 and organizing thrombi and lower counts are observed in association with fully organized thrombi.7) The best known immunologic stimulus leading to degranu- lation of human mast cells is their activation when the immunoglobulin E (IgE) molecules on their surfaces bind a relevant antigen.8) If mast cells are actively involved in atherosclerotic plaques, they must be activated by stent implantation which will cause stretching and overdilation of the diseased vessel wall. This reaction should be associated with an increased response of IgE which plays a predominant role in activation and degranulation of mast cells. Plasma levels of CRP after coronary artery stenting could also be a marker of the intensity of the inflammatory reaction. In light of the above-mentioned assumptions and to pro- vide baseline data for further studies regarding stenting, restenosis, and the inflammatory response, we prospectively conducted a clinical study to investi- gate the time-related response of plasma levels of IgE and CRP, which are two different inflammatory markers mediated by different cytokines, in stable patients who underwent elective coronary artery stenting. METHODS Study population: Our study group consisted of 13 consecutive patients with chronic stable angina pectoris (Canadian Cardiovascular Society, Class II-III) who fulfilled the inclusion criteria and underwent successful coronary artery stenting procedures in elective conditions. All patients had at least 1-vessel coro- nary artery disease involvement defined as a 70% reduction of the luminal dia- meter in major epicardial arteries. Patients with acute coronary syndromes (myo- cardial infarction and unstable angina within 2 months), significant valvular heart disease, myocarditis, cardiomyopathies, hepatic and renal disease, acute infec- tion, collagenosis, malignancy, anti-inflammatory drug usage, any history of hay fever; asthma, allergic rhinitis or eczema; allergy to grasses, house dust, cats or dogs; asthma, allergic rhinitis or eczema in parents and positive skin allergy test results were excluded from the study. Biochemical tests and study design: Plasma CRP (mg/dL) and IgE (IU/mL) lev- els were determined before and after stent implantation on days 1, 2, 3, and 4 and at the end of the first and third month. Preprocedure CRP levels of all patients were normal (≤ 0.5 mg/dL). Plasma samples were immediately analyzed for CRP concentration that was determined with a nephelometric system (Behring Nephelometer 100 Analyser, Marburg, Germany). The normal upper reference value for CRP with this method is up to 0.5 mg/dL. Due to technical difficulty in quantitatively analyzing CRP concentrations less than 0.5 mg/dL, values less than this cutoff level were taken as 0.5 mg/dL in further calculations and compar- isons. Screening for allergy was conducted using an Immulite Allergy Food Panel FP5E (Diagnostic Products Corporation, Los Angeles, CA, USA) which is a Vo l 4 4 No 5 INFLAMMATION AND CORONARY ARTERY STENTING 595 chemiluminescent enzyme-labeled immunoassay designed for clinical use with the Immulite automated immunoassay analyzer for the qualitative detection of IgE antibody specific serum to a panel of food allergens: F1 (egg white), F2 (milk), F3 (codfish), F4 (wheat), F13 (peanut), and F14 (soybean). Patient serum was then analyzed with an Immulite AlaTop Allergy Screen (Diagnostic Products Corporation) for the detection of IgE antibodies specific to inhalant allergens in serum. Both tests were intended for in vitro diagnostic use as an aid in the differ- ential diagnosis of IgE-mediated allergic disorders and atopic allergy. Both tests were sufficiently sensitive and specific (99.1% and 95.7%, respectively) to be able to qualitatively differentiate IgE-mediated allergic status.9) Only patients with negative test results were included in the study. IgE determination was per- formed using an Immulite total IgE system (Diagnostic Products Corporation) which is a solid phase, two-site chemiluminescent immunometric assay. For cre- atine kinase MB (CK-MB) venous blood samples were obtained immediately before and one day after the procedure. Plasma samples for CK-MB were ana- lyzed with commercially available immunochemical tests. Angioplasty and stent procedures were performed using conventional techniques. Only one stent was implanted in each patient. Medtronic AVE and Bestent 9-18 mm (n = 5), Cordis Crown and LP 12-18 mm (n = 4), and Jomed Jostent 12-19 mm (n = 4) stents were used. All stents were overdilated at high pressures. The type of angiographic lesion was determined according to ACC/AHA criteria.10) Procedural success was defined as residual stenosis < 30% in the worse of two orthogonal views, as assessed by quantitative analysis and normal runoff of the contrast medium in the stented vessel, and absence of death, myocardial infarction, and the need for fur- ther revascularization procedures during the hospital stay. Statistical analysis: Data are presented as the mean ± SD. Two-way Friedman repeated-measures analysis of variance was used for comparison of repeated vari- ables in one particular group and the Wilcoxon signed-ranks test was used for post hoc analysis of differences between two continuous variables in the same group. Statistica for Windows (version 4.3) was used for statistical tests and anal- ysis. A P < 0.05 was considered statistically significant. RESULTS The clinical characteristics of all study patients who underwent coronary artery stenting are presented in Table I. All patients underwent successful stent implantation without any demonstrable complications. The patients were closely followed through a three-month period for ensuing symptoms and coronary events. Only two patients complained of recurrent angina during the follow-up period. One with a left anterior descending coronary artery stent underwent coro- Jpn Heart J 596 ERDOGAN, ET AL September 2003 nary artery bypass surgery, and the other with a right coronary artery stent was medically treated for in-stent restenosis. As shown in Table II, the mean prepro- Table I. Clinical and Angiographic Characterisics of the Study Patientsa Patients (n)13 Men (%) 92 Age (years) 58 ± 8 Risk factors Diabetes (%) 0 Hypertension (%) 62 Smoking (%) 54 Hypercholesterolemia (%) 54 Family History (%) 15 History of old MI (%) 43 Total C (mg/dL) 221 ± 53 LDL-C (mg/dL) 136 ± 44 HDL-C (mg/dL) 45 ± 10 Triglyceride (mg/dL) 183 ± 115 Ejection fraction (%) 64 ± 12 Coronary angiography One-vessel disease (%) 69 Two-vessel disease (%) 23 Three-vessel disease (%) 8 Stented vessel LAD (%) 54 RCA (%) 38 CX (%) 8 Lesion type Type A (%) 69 Type B (%) 31 a Values are presented as mean ± SD.; MI = myocardial infarction; C = cholesterol; LAD = left anterior descend- ing artery; RCA
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