title: Elevated levels of neopterin are associated with carotid plaques with complex morphology in patients with stable angina pectoris.
abstract: OBJECTIVE
  Neopterin is an activation marker for monocytes/macrophages, and circulating levels of neopterin are elevated in patients with coronary complex lesions in unstable angina pectoris. We investigated the possible association between neopterin and complex carotid plaques which may be associated with the risk of ischemic stroke in patients with stable angina pectoris (SAP).
  
  
  METHODS
  We measured plasma levels of neopterin in 102 patients with SAP and carotid ultrasound was performed for evaluation of the presence of carotid plaques and plaque surface characteristics categorized as complex or noncomplex. In addition, endarterectomy specimens of extracranial high-grade carotid stenosis with complex plaques from five patients with SAP were immunohistochemically examined with antibodies to smooth muscle cells, endothelial cells, platelets, macrophages, and T cells.
  
  
  RESULTS
  Plasma neopterin levels were significantly higher in patients with complex carotid plaques than in those with noncomplex plaques (median [interquartile range]: 24.2 [19.2-39.3]nmol/L vs. 19.4 [11.9-25.1]nmol/L; P=0.01) or without any plaques (18.8 [14.9-23.6]nmol/L; P=0.001). On multivariate logistic analyses after adjustment for traditional atherosclerotic risk factors, multi-vessel coronary disease and high sensitivity C-reactive protein, neopterin levels were independently associated with the presence of complex carotid plaques (adjusted OR 2.21 per SD increase, 95%CI 1.13-4.33, P=0.02). Immunohistochemical staining revealed abundant neopterin-positive macrophages in carotid complex lesions.
  
  
  CONCLUSIONS
  These findings demonstrate that carotid plaques with complex morphology have increased circulating neopterin levels and immunohistochemical localization of neopterin in patients with SAP. Neopterin can be considered an important biomarker of plaque destabilization in carotid artery atherosclerotic lesions in this population.
authors.affiliation: Department of Internal Medicine and Cardiology, Osaka City University Graduate School of Medicine, Osaka, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sugioka
authors.forename: Takahiko
authors.initials: T
authors.lastname: Naruko
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hozumi
authors.forename: Masashi
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Chizuko
authors.initials: C
authors.lastname: Kitabayashi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ikura
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Shirai
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Matsumura
authors.forename: Shoichi
authors.initials: S
authors.lastname: Ehara
authors.forename: Keiji
authors.initials: K
authors.lastname: Ujino
authors.forename: Akira
authors.initials: A
authors.lastname: Itoh
authors.forename: Kazuo
authors.initials: K
authors.lastname: Haze
authors.forename: Anton E
authors.initials: AE
authors.lastname: Becker
authors.forename: Minoru
authors.initials: M
authors.lastname: Yoshiyama
authors.forename: Makiko
authors.initials: M
authors.lastname: Ueda
mesh_terms: D000368:Aged; D000787:Angina Pectoris / Q000378:metabolism*; D050197:Atherosclerosis / Q000097:blood; D002097:C-Reactive Protein / Q000096:biosynthesis; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000378:metabolism*; D003251:Constriction, Pathologic; D005260:Female; D006801:Humans; D007511:Ischemia / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D019798:Neopterin / Q000097:blood*; D012306:Risk; D012307:Risk Factors; D020521:Stroke / Q000378:metabolism; D014463:Ultrasonography / Q000379:methods
chemical_list: D019798:Neopterin; D002097:C-Reactive Protein