Clopidogrel is an effective and specific inhibitor of ADP-induced platelet aggregation. After metabolic activation, the active clopidogrel metabolite irreversibly impairs the human platelet P2Y12 ADP receptor. Gialpha-protein activation and inhibition of vasodilator-stimulated phosphoprotein (VASP) phosphorylation are two key elements of the P2Y12 receptor pathway suitable for quantitation of clopidogrel effects. So far, only limited data exist about a diminished responsiveness to clopidogrel and underlying possible mechanisms. We investigated clopidogrel effects in 57 patients after percutaneous coronary intervention and stent implantation by flow cytometry for the analysis of intracellular VASP phosphorylation. Patients were treated with a 300 mg clopidogrel loading dose, followed by 75 mg/day clopidogrel in combination with 100 mg/day aspirin. Samples were drawn after a median of 5 days of clopidogrel treatment. Considerable differences in the responsiveness to clopidogrel could be observed and it was shown that 17.5% (10/57) of the patients revealed an inadequate responsiveness to clopidogrel despite continuation of clopidogrel intake. Comparable amounts of Gialpha and VASP were found in two clopidogrel low-responding patients as well as in two responding patients. To exclude a molecular defect of P2Y12 ADP receptor, the P2Y12 receptor gene of eight clopidogrel treated patients (seven patients with inadequate responsiveness, one responder) was sequenced. We only found a single silent mutation in exon 2 at position 1828 (GA). We suggest that individual differences in clopidogrel metabolization could cause relevant variations in clopidogrel responsiveness despite the use of a 300 mg clopidogrel loading dose.

Background and Purpose-This study sought to determine the frequency of noncircular lumens in patients with significant carotid atherosclerotic disease and to evaluate the effect of noncircular lumens on stenosis measurement derived from angiographic projections. Methods-One hundred consecutive patients presenting with an internal carotid artery stenosis of at least 50% were imaged with spiral CT angiography. The transverse morphology of the diseased lumen was assessed on axial images, and the frequency of noncircular lumens was determined. In these cases, maximum intensity projection angiograms were reconstructed in standardized angiographic planes and in a plane selected according to the luminal obliquity, which was chosen to optimize the angiographic representation of the maximal stenosis. North American Symptomatic Carotid Endarterectomy Trial (NASCET) measurements were calculated from the maximum intensity projection images, and differences between values obtained from standard and optimized projections were recorded. Results-Noncircular lumens were observed in 18 of 100 patients and consisted of elliptical and linear transverse profiles.The transverse orientation of the lumen in these cases ranged from ϩ90°to Ϫ87°relative to the anteroposterior plane. An increase in the calculated NASCET stenosis was demonstrated when measurements were obtained from angiographic reconstructions obtained in the exact plane of the luminal obliquity compared with standard angiographic projections. As a result, the stenosis severity was upgraded from moderate to severe in 2 patients. Conclusions-Noncircular

significant and extended wall thickening is commonly present in the internal and common carotid arteries of patients with atherosclerotic disease, but the internal carotid artery is significantly less affected than the common carotid artery. These observations question the validity of using the common carotid artery as a reference vessel for angiographic stenosis measurements.