Elevated levels of C-reactive protein before coronary artery bypass grafting predict recurrence of ischemic events

R studies have shown an involvement of the inflammatory system in the pathogenesis of ischemic heart disease, and markers of inflammation were found to be correlated with prognosis.1–4 In unstable angina, elevated serum levels of C-reactive protein (CRP), an aspecific but sensitive marker of inflammation, were found to have a short-term prognostic value unrelated to myocardial cell damage, myocardial ischemia, or activation of the hemostatic system.3,5,6 The long-term prognostic value of elevated CRP levels was reported in patients with stable or unstable coronary artery disease,4,7,8 and in healthy subjects with high9,10 and low levels11 of coronary risk factors. Several randomized and observational studies have identified the variables relevant to patients’ prognosis after coronary artery bypass grafting (CABG),12–15 but none of these studies have identified a serologic marker of long-term outcome or have considered the role of the inflammatory system in patients with CABG. We studied 86 patients with stable or unstable ischemic heart disease who underwent CABG to ascertain whether an activation of the inflammatory system before surgery, detected by elevated serum levels of CRP, was associated with prognosis. • • • We studied patients who underwent elective CABG in the Department of Cardiac Surgery between June 1992, and July 1998, and in whom an ultrasensitive measurement of CRP before surgery was available. Patients with a history of recent or ongoing infective or inflammatory diseases, thrombotic disorders, recent (,3 weeks) myocardial infarction were excluded. We also excluded patients with severely depressed cardiac function and those aged .75 years of age, because they have an elevated basal risk,16 and patients who had had concomitant valve procedures or resection of a left ventricular aneurysm. Seventy-one patients were symptomatic for unstable angina and 15 patients for chronic stable angina. Forty-one patients had had a previous acute myocardial infarction. Sixty-one patients had good left ventricular contractility (measured as ejection fraction by transthoracic echocardiography), 16 had a mild reduction, and 9 a moderate reduction. At coronary angiography 8 patients had left anterior descending disease, 9 had left main stem disease, 25 had 2-vessel disease and 44 had 3-vessel disease. Eight patients underwent previous revascularization procedures, 5 CABG, and 3 percutaneous transluminal coronary angioplasty. All clinical and demographic characteristics of the patients are described in Table I. Peripheral blood samples were obtained on hospital admission. Plasma aliquots of 500 ml were pipetted in appropriate tubes and stored at 280°C.17 CRP was assayed by an ultrasensitive CRP assay by nephelometry (Dade Behring, BN-II, Marburg, Germany) in a single batch at the end of the study. The study protocol was approved by the ethics committee of our university and all patients gave their consent to use part of their blood for CRP measurement. After induction of anesthesia, the principles of the warm heart surgery technique were followed.18 All patients underwent perfusion in normothermia while myocardial protection was achieved with intermittent anterograde warm blood cardioplegia. Distal and proximal anastomoses were performed during a single prolonged aortic cross-clamp period. We considered both early (in-hospital) and late From the Institute of Cardiology, Institute of Cardiac Surgery, and Institute of Anaesthesiology, Catholic University of the Sacred Heart, Rome, Italy. This study was supported in part by the European Community (Biomed 2 Research Grant PL 951502) and in part by the Fondazione Internazionale di Ricerca per il Cuore onlus. Dr. Biasucci’s address is: Istituto di Cardiologia, Universita’ Cattolica del S. Cuore, Largo Francesco Vito 1, 00168 Rome, Italy. E-mail: biasucci @pelagus.it. Manuscript received November 16, 1998; revised manuscript received and accepted April 5, 1999. TABLE I Clinical and Demographic Characteristics of Patients