title: Persistent systemic inflammation in unstable angina is largely unrelated to the atherothrombotic burden.
abstract: OBJECTIVE
  The aim of this study was to assess the relationship between systemic inflammation, atherosclerosis, and thrombosis in two distinct clinical models of atherothrombosis.
  
  
  BACKGROUND
  Persistent unstable angina (UA) is commonly associated with coronary thrombosis and persistent systemic inflammation.
  
  
  METHODS
  We assessed circulating markers of activation of the thrombotic and fibrinolytic cascades and systemic soluble and cellular markers of inflammation on admission in 40 patients with persisting UA (Braunwald class IIIB; group 1) and 30 patients with Leriche-Fontaine stage IIB-III peripheral artery disease awaiting revascularization (group 2).
  
  
  RESULTS
  The extent of atherosclerosis (p < 0.01) and activation of the coagulation system were greater in group 2, which had higher thrombin-antithrombin III complexes and D-dimer levels (2.7 and 24.4 microg/l, respectively), than in group 1 (2.0 microg/l and 12.9 microg/l, p = 0.02 and p = 0.0001, respectively). In contrast, C-reactive protein and interleukin-6 levels were higher in group 1 (7.6 pg/ml and 7.8 pg/ml, respectively) than in group 2 (4.5 pg/ml and 3.0 pg/ml, p < 0.01 and p = 0.03, respectively). Moreover, neutrophil activation was only found in group 1 (neutrophil myeloperoxidase content -4.0 arbitrary units vs. +3.4 arbitrary units in group 2, p < 0.0001). These differences persisted during the initial three days of hospitalization.
  
  
  CONCLUSIONS
  Such a large, consistent discrepancy between atherothrombotic burden and systemic inflammation suggests that atherothrombosis, by itself, is an unlikely cause of persisting, recurring UA. An understanding of the primary inflammatory mechanisms of persistent and recurrent coronary instability could open the way to novel therapeutic strategies.
authors.affiliation: Cytokine Biology of Vessels, Kennedy Institute of Rheumatology and Surgery, Anesthetics and Intensive Care, Faculty of Medicine, Imperial College, London, United Kingdom.
authors.forename: Claudia
authors.initials: C
authors.lastname: Monaco
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Rossi
authors.forename: Diego
authors.initials: D
authors.lastname: Milazzo
authors.forename: Franco
authors.initials: F
authors.lastname: Citterio
authors.forename: Francesca
authors.initials: F
authors.lastname: Ginnetti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: D'Onofrio
authors.forename: Domenico
authors.initials: D
authors.lastname: Cianflone
authors.forename: Filippo
authors.initials: F
authors.lastname: Crea
authors.forename: Luigi M
authors.initials: LM
authors.lastname: Biasucci
authors.forename: Attilio
authors.initials: A
authors.lastname: Maseri
mesh_terms: D000368:Aged; D000789:Angina, Unstable / Q000097:blood* / Q000209:etiology; D000907:Antibodies, Bacterial / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D000990:Antithrombin III; D002097:C-Reactive Protein / Q000378:metabolism; D016993:Chlamydophila pneumoniae / Q000276:immunology; D003587:Cytomegalovirus / Q000276:immunology; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D016480:Helicobacter pylori / Q000276:immunology; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D010447:Peptide Hydrolases / Q000097:blood; D016491:Peripheral Vascular Diseases / Q000097:blood* / Q000209:etiology; D011516:Prothrombin
chemical_list: D000907:Antibodies, Bacterial; D000914:Antibodies, Viral; D005338:Fibrin Fibrinogen Degradation Products; D015850:Interleukin-6; D010446:Peptide Fragments; C046193:antithrombin III-protease complex; C036309:fibrin fragment D; C045879:prothrombin fragment 1.2; D000990:Antithrombin III; D011516:Prothrombin; D002097:C-Reactive Protein; D010447:Peptide Hydrolases