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Submitted on December 29, 2003
Accepted on February 27, 2004
From the Institute of Internal Medicine (P.M.) and Vascular Surgery (P.P., G.M.M., F.P.), Medical University of Sassari, Sassari, Italy; the Experimental Medicine and Gene Therapy Section (C.E., E.D., P.M.), National Institute of Biostructures and Biosystems, Osilo, Italy; and the Department of Biochemistry and Molecular Biology, Medical University of South Carolina (L.C., J.C.), Charleston, SC.
* To whom correspondence should be addressed. E-mail: madeddu{at}yahoo.com.
Background--Vascular growth factors are upregulated in stroke patients, but it remains unknown if they correlate with carotid atherosclerosis.
Methods and Results--A case-control study was conducted to determine: (1) possible association between biomarkers of angiogenesis or inflammation and carotid stenosis; and (2) the impact of revascularization on the same biomarkers. Circulating vascular endothelial growth factor (VEGF), basic fibroblast GF (bFGF), tissue kallikrein (tK), and high-sensitivity C-reactive protein (hs-CRP) were measured in 89 patients with carotid obstruction and 45 age-matched controls. Patients were stratified as <50% carotid stenosis (CAS; n=16); 50% to 69% CAS (n=12); 70% to 99% CAS (n=43); and carotid occlusion (CAO; n=18). No association was found between VEGF, bFGF, or hs-CRP and obstruction grading. TK augmented from 360±30 in <50% CAS (P=NS versus controls) to 509±72 in moderate CAS (P<0.05), 1159±178 in high-grade CAS (P<0.02), and 1616±403 pg/mL in CAO (P<0.01). A threshold of 508 pg/mL provided the maximized predictive value of high-grade obstruction. After revascularization, tK decreased from 1410±352 to 782±86 pg/mL (P<0.01), whereas no change was detected in nonoperated. Hs-CRP was unaffected by revascularization.
Conclusions--Angiogenic factors are heterogeneously expressed in patients with carotid atherosclerosis. The tK measurement may be useful for the diagnosis and monitoring of atherosclerotic disease.
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