Objectives-Thiazolidinediones, such as rosiglitazone, have been shown to retard atherosclerosis disease progression in diabetic subjects. These agents may have anti-atherosclerotic effects through direct inhibition of inflammatory processes in the vessel wall, and so their benefit may extend to patients with atherosclerotic disease, even in the absence of diabetes. In this study, we assessed the effect of rosiglitazone on common carotid intima-media thickness (IMT) progression in nondiabetic coronary artery disease (CAD) patients. Methods and Results-Consecutive subjects (nϭ92) with clinically stable, angiographically documented CAD and without diabetes mellitus were randomized in a double-blind manner to receive placebo or rosiglitazone for 48 weeks. They received single-dose placebo and rosiglitazone 4 mg daily for the initial 8 weeks, and the doses were doubled for the remainder of the study. Common carotid IMT together with fasting glucose, insulin, and lipid profile were measured at baseline and repeated after 24 and 48 weeks. Rosiglitazone-treated patients showed reduced IMT progression compared with the placebo group, Ϫ0.012 mm/48 weeks versus 0.031 mm/48 weeks (Pϭ0.03). Rosiglitazone treatment significantly reduced insulin resistance, estimated by homeostasis model of insulin resistance index, compared with placebo (Pϭ0.01). Key Words: PPAR-␥ Ⅲ agonists Ⅲ thiazolidinediones Ⅲ carotid intima-media thickness Ⅲ coronary artery disease. Conclusions-RosiglitazoneT he thiazolidinedione rosiglitazone, a peroxisome proliferator-activated receptor-␥ (PPAR-␥) agonist, is an insulin-sensitizing agent and is used in the treatment of type 2 diabetes mellitus. Data suggest that these agents may also retard atherosclerotic disease progression. Thiazolidinediones have been shown to reduce atherosclerotic lesion area in mouse models of atherosclerosis that exhibit hyperlipidemia and insulin-resistance. 1-3 Thiazolidinediones have also been reported to reduce common carotid arterial intima-media thickness (IMT) progression, a surrogate index of atherosclerotic disease progression, in type 2 diabetic subjects. 4,5 These results taken together suggest that insulin sensitization and glucose-lowering are important mechanisms underlying the antiatherogenic effects of these agents. [1][2][3][4][5] See page 798However, recent evidence suggests that PPAR-␥ agonists may also inhibit atherosclerotic disease progression by exerting anti-inflammatory effects within the artery wall. 6,7 Therefore, the potential antiatherogenic effects of PPAR-␥ agonists may not be confined to type 2 diabetic patients. 8 The PPAR-␥ agonist troglitazone has been shown to reduce atherosclerotic lesion formation and macrophage accumulation in plaques in nondiabetic low-density lipoprotein (LDL) receptor-deficient mice. 9 We recently found that rosiglitazone reduces circulating markers of inflammation, such as C-reactive protein, in nondiabetic patients with coronary artery disease (CAD). 10 In the present study, we measured the effect of treatment on com...

Intravenous L-arginine and GSNO attenuate Doppler embolic signals in humans. Modulation of the NO system with these agents may have applications in the treatment of thromboembolic disease. This study demonstrates the potential application of ultrasonic embolic signal detection to examine the efficacy of new antiplatelet agents in relatively small numbers of patients.

Background and Purpose-The clinical application of Doppler detection of circulating cerebral emboli will depend on a reliable automated system of embolic signal detection; such a system is not currently available. Previous studies have shown that frequency filtering increases the ratio of embolic signal to background signal intensity and that the incorporation of such an approach into an offline automated detection system markedly improved performance. In this study, we evaluated an online version of the system. In a single-center study, we compared its performance with that of a human expert on data from 2 clinical situations, carotid stenosis and the period immediately after carotid endarterectomy. Because the human expert is currently the "gold standard" for embolic signal detection, we also compared the performance of the system with an international panel of human experts in a multicenter study. Methods-In the single-center evaluation, the performance of the software was tested against that of a human expert on 20 hours of data from 21 patients with carotid stenosis and 18 hours of data from 9 patients that was recorded after carotid endarterectomy. For the multicenter evaluation, a separate 2-hour data set, recorded from 5 patients after carotid endarterectomy, was analyzed by 6 different human experts using the same equipment and by the software. Agreement was assessed by determining the probability of agreement. Results-In the 20 hours of carotid stenosis data, there were 140 embolic signals with an intensity of Ն7 dB. With the software set at a confidence threshold of 60%, a sensitivity of 85.7% and a specificity of 88.9% for detection of embolic signals were obtained. At higher confidence thresholds, a specificity Ͼ95% could be obtained, but this was at the expense of a lower sensitivity. In the 18 hours of post-carotid endarterectomy data, there were 411 embolic signals of Ն7-dB intensity. When the same confidence threshold was used, a sensitivity of 95.4% and a specificity of 97.5% were obtained. In the multicenter evaluation, a total of 127 events were recorded as embolic signals by at least 1 center. The total number of embolic signals detected by the 6 different centers was 84, 93, 108, 92, 63, and 78. The software set at a confidence threshold of 60% detected 90 events as embolic signals. The mean probability of agreement, including all human experts and the software, was 0.83, and this was higher than that for 2 human experts and lower than that for 4 human experts. The mean values for the 6 human observers were averaged to give Pϭ0.84, which was similar to that of the software. Conclusions-By using the frequency specificity of the intensity increase occurring with embolic signals, we have developed an automated detection system with a much improved sensitivity. Its performance was equal to that of some human experts and only slightly below the mean performance of a panel of human experts (Stroke. 2000;31:1335-1341.)