title: Circulating fibrocytes as predictors of adverse events in unstable angina.
abstract: Half of the patients who present with unstable angina (UA) develop recurrent symptoms over the subsequent year. Identification of patients destined to develop such adverse events would be clinically valuable, but current tools do not allow for this discrimination. Fibrocytes are bone marrow-derived progenitor cells that co-express markers of leukocytes and fibroblasts and are released into the circulation in the context of tissue injury. We hypothesized that, in patients with UA, the number of circulating fibrocytes predicts subsequent adverse events. We enrolled 55 subjects with UA, 18 with chronic stable angina, and 22 controls and correlated their concentration of circulating fibrocytes to clinical events (recurrent angina, myocardial infarction, revascularization, or death) over the subsequent year. Subjects with UA had a >2-fold higher median concentration of both total and activated fibrocytes compared with subjects with chronic stable angina and controls. In UA subjects, the concentration of total fibrocytes identified those who developed recurrent angina requiring revascularization (time-dependent area under the curve 0.85) and was superior to risk stratification using thrombolysis in myocardial infarction risk score and N-terminal pro B-type natriuretic peptide levels (area under the curve, 0.53 and 0.56, respectively, P < 0.001). After multivariable adjustment for thrombolysis in myocardial infarction predicted death, MI, or recurrent ischemia, total fibrocyte level was associated with recurrent angina (hazard ratio, 1.016 per 10,000 cells/mL increase; 95% confidence interval, 1.007-1.024; P < 0.001). Circulating fibrocytes are elevated in patients with UA and successfully risk stratify them for adverse clinical outcomes. Fibrocytes may represent a novel biomarker of outcome in this population.
authors.affiliation: Department of Medicine, University of Virginia, Charlottesville, Va; Division of Cardiology, University of Virginia, Charlottesville, Va. Electronic address: keeley@virginia.edu.
authors.forename: Ellen C
authors.initials: EC
authors.lastname: Keeley
authors.affiliation: Houston Methodist DeBakey Heart & Vascular Center, Houston, Tex.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Schutt
authors.affiliation: Department of Medicine, University of Virginia, Charlottesville, Va.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Marinescu
authors.affiliation: Department of Medicine, University of Virginia, Charlottesville, Va; Division of Pulmonary and Critical Care Medicine, University of Virginia, Charlottesville, Va.
authors.forename: Marie D
authors.initials: MD
authors.lastname: Burdick
authors.affiliation: Department of Medicine, University of Virginia, Charlottesville, Va; Division of Pulmonary and Critical Care Medicine, University of Virginia, Charlottesville, Va.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Strieter
authors.affiliation: Department of Medicine, University of Virginia, Charlottesville, Va; Division of Pulmonary and Critical Care Medicine, University of Virginia, Charlottesville, Va; The Carter Center for Immunology, University of Virginia, Charlottesville, Va.
authors.forename: Borna
authors.initials: B
authors.lastname: Mehrad
mesh_terms: D000328:Adult; D000368:Aged; D000789:Angina, Unstable / Q000097:blood / Q000473:pathology*; D016022:Case-Control Studies; D002465:Cell Movement; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D012008:Recurrence; D053773:Transforming Growth Factor beta1 / Q000097:blood
chemical_list: D053773:Transforming Growth Factor beta1