Circulating tissue kallikrein levels correlate with severity of carotid atherosclerosis

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 cases. 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.