Elevated levels of neopterin are associated with carotid plaques with complex morphology in patients with stable angina pectoris.
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.
Sugioka
Kenichi
K
Department of Internal Medicine and Cardiology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Naruko
Takahiko
T
Hozumi
Takeshi
T
Nakagawa
Masashi
M
Kitabayashi
Chizuko
C
Ikura
Yoshihiro
Y
Shirai
Nobuyuki
N
Matsumura
Yoshiki
Y
Ehara
Shoichi
S
Ujino
Keiji
K
Itoh
Akira
A
Haze
Kazuo
K
Becker
Anton E
AE
Yoshiyama
Minoru
M
Ueda
Makiko
M
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
D019798:Neopterin; D002097:C-Reactive Protein