S case-control and prospective studies have reported that increased white blood cell (WBC) count is an independent risk factor for coronary heart disease, cardiovascular events, and mortality.1–4 An elevated WBC count has been associated with both a higher risk of developing myocardial infarction and worse outcome in post–myocardial infarction patients.5–7 It has been also reported that relative lymphocyte count may have prognostic significance in patients with known or suspected coronary heart disease.8,9 However, the relation between WBC count and prognosis in patients with unstable angina has not been investigated systematically. In acute coronary syndromes, markers of increased risk, such as cardiac troponin-I exist, which have been shown to be useful for patient risk stratification.10,11 This study assesses the prognostic value of total and differential WBC counts in patients presenting with unstable angina. • • • We studied 71 consecutive patients (44 men) who were admitted to our coronary care unit between September 1996 and June 1997 with the diagnosis of unstable angina (class II-B and III-B according to the Braunwald classification).12 As a control group for baseline WBC measurements, we examined 118 patients (84 men) with chronic stable angina who were admitted for routine coronary arteriography. Patients with unstable angina received conventional treatment with nitrates, heparin, b-adrenergic blockers, calcium antagonists, and aspirin. Clinical decisions were left to the discretion of the managing cardiologist. All patients with unstable angina were followed up for 1 year, or up to the time of elective coronary revascularization in patients who were put on a waiting list for this purpose before hospital discharge. The following were considered to represent study end points: (1) new admission to coronary care unit with unstable angina (Braunwald III-B)12 requiring intravenous drug administration and/or revascularization, (2) myocardial infarction diagnosed according to World Health Organization criteria, and (c) cardiac death. Stable angina was defined as typical exertional chest pain relieved by rest and/or nitrate administration. In all patients with exertional angina, symptoms were stable for at least 3 months before study entry. Exclusion criteria that applied to both groups of patients were: recent (,12 weeks) myocardial infarction, evidence of active infectious disease, inflammatory or immunologic disorders, recent major surgery or trauma, known or suspected neoplastic diseases, treatment with anti-inflammatory or immunosuppressive drugs, renal failure, significant valvular heart disease, and severe heart failure. All patients gave written informed consent before study entry and the study was approved by the local ethics committee. In patients with unstable angina, total and differential WBC counts were measured in morning fasting blood samples withdrawn within the first 24 hours after admission. In those with stable angina, measurements were obtained in fasting blood samples drawn in the morning before coronary angiography. Total and differential WBC counts were determined by a commercially available automated system (STKS Coulter, Beckman Coulters, High Wycombe, United Kingdom) that uses a sample size of up to 8,000 cells. In patients with unstable angina, cardiac troponin-I was measured using a commercially available high-sensitivity immunoassay (AxSYM system, Abbott Laboratories, Abbott Park, Illinois). The value of 0.4 mg/L demonstrating a 95th percentile value of troponin-I measurement in serum from 52 healthy blood donors was subsequently used as the threshold for the analysis. Variables are expressed as mean 6 SD. Odds ratio are expressed with their 95% confidence interval. Proportions have been compared using the chi-square test or 2-tailed Fisher’s exact test. Continuous variables were analyzed using unpaired t tests and Mann-Whitney U tests when appropriate. Logistic regression was used to calculate odds ratio between lymphocyte quartiles. The Cox regression model was used to assess adjusted time-to-event rate curves, where the dependent variable was a risk marker (defined as abnormal cardiac troponin-I and lymphocyte count ,2.40 3 10 lymphocytes/L) and the independent variables were those with p ,0.20 in the univariate analysis. A probability ,0.05 was considered statistically significant. The baseline characteristics of patients with stable and unstable angina are presented in Table I. Unstable angina patients had both higher neutrophil and relative monocyte counts than patients with chronic stable angina. These differences, however, were not statistically significant when adjusted for gender, history of diabetes, past history of myocardial infarction, hypertension, and cholesterol levels (p 5 0.10 and p 5 0.35, respectively). The mean duration of follow-up for unstable angina patients was 13 6 2 months. During that period, 22 unstable angina patients had cardiac events: 18 were readmitted with a new episode of From the Department of Cardiological Sciences, St George’s Hospital Medical School, London, United Kingdom. Prof. Kaski’s address is: Department of Cardiological Sciences, St. George’s Hospital Medical School, Cranmer Terrace, London SW17 0RE, United Kingdom. E-mail: jkaski@sghms.ac.uk. Manuscript received November 22, 1999; revised manuscript received and accepted February 29, 2000.
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