title: Multimarker approach in discriminating patients with symptomatic and asymptomatic atherosclerotic carotid artery stenosis.
abstract: OBJECTIVE
  Several circulating biomarkers have been implicated in carotid atherosclerotic plaque rupture and thrombosis; however, their clinical utility remains unknown. The aim of this study was to determine the role of a large biomarker panel in the discrimination of symptomatic (S) vs. asymptomatic (A/S) subjects in a contemporary population with carotid artery stenosis (CS).
  
  
  METHODS
  Prospective sampling of circulating cytokines and blood lipids was performed in 300 unselected, consecutive patients with ≥50% CS, as assessed by duplex ultrasound (age 47-83 years; 110 with A/S and 190 with S) who were referred for potential CS revascularization.
  
  
  RESULTS
  CS severity and pharmacotherapy did not differ between the A/S and S patients. The median values of total cholesterol, low-density lipoprotein cholesterol, and lipoprotein(a) did not differ, but high-density lipoprotein (HDL) cholesterol was significantly higher (p<0.001) and triglycerides were lower (p=0.03) in the A/S-CS group than in the S-CS group. Interleukin-6 (IL-6) and high-sensitivity C-reactive protein were higher (p=0.04 and p=0.07, respectively) in the S-CS group. Circulating visfatin, soluble CD 40 receptor ligand, soluble vascular cell adhesion molecule, leptin, adiponectin, IL-1β, IL-8, IL-18, monocyte chemoattractant protein-1, myeloperoxidase, matrix metalloproteinases-8, -9, and -10, and fibrinogen were similar, but tissue inhibitor of matrix metalloproteinases-1 (TIMP) was reduced in S-CS compared to A/S-CS (p=0.02). Nevertheless, incorporation of TIMP and IL-6 did not improve the HDL-cholesterol receiver operating characteristics for S-CS status prediction. S-CS status was unrelated to angiographic stenosis severity or plaque burden, as assessed by intravascular ultrasound (p=0.16 and p=0.67, respectively). Multivariate logistic regression analysis revealed low HDL-cholesterol to be the only independent predictor of CS symptoms, with an odds ratio of 1.81 (95% confidence interval=1.15-2.84, p=0.01) for HDL <1.00 mmol/L (first quartile) vs. >1.37 (third quartile). In S-CS, osteoprotegerin and lipoprotein-associated phospholipase A2 (Lp-PLA2) were elevated in those with recent vs. remote symptoms (p=0.01 and p=0.02, respectively).
  
  
  CONCLUSIONS
  In an all-comer CS population on contemporary pharmacotherapy, low HDL-cholesterol (but not other previously implicated or several novel circulating biomarkers) is an independent predictor of S-CS status. In addition, an increase in circulating osteoprotegerin and Lp-PLA2 may transiently indicate S transformation of the carotid atherosclerotic plaque.
authors.affiliation: Jagiellonian University Department of Cardiac and Vascular Diseases, Krakow, Poland. ; John Paul II Hospital, Krakow, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Musialek
authors.forename: Wieslawa
authors.initials: W
authors.lastname: Tracz
authors.forename: Lukasz
authors.initials: L
authors.lastname: Tekieli
authors.forename: Piotr
authors.initials: P
authors.lastname: Pieniazek
authors.forename: Anna
authors.initials: A
authors.lastname: Kablak-Ziembicka
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Przewlocki
authors.forename: Ewa
authors.initials: E
authors.lastname: Stepien
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Kapusta
authors.forename: Rafal
authors.initials: R
authors.lastname: Motyl
authors.forename: Jakub
authors.initials: J
authors.lastname: Stepniewski
authors.forename: Anetta
authors.initials: A
authors.lastname: Undas
authors.forename: Piotr
authors.initials: P
authors.lastname: Podolec
keywords: HDL-cholesterol; biomarkers; carotid artery stenosis; circulating cytokines; risk factors; stroke risk
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