The planning of revascularization strategy for multivessel coronary artery disease (CAD) in nondiabetic patients is optimally made through considering the goals of improving survival and/or relieving symptoms. Existing clinical practice guidelines and appropriate use criteria (1–3) state that in nondiabetic patients with multivessel CAD and stable ischemic heart disease (SIHD), either coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) with drug-eluting stents may be used for those with low SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) scores, but CABG is preferred for those with intermediate or high SYNTAX scores. In the overall SYNTAX population (4–6), the rates of death and stroke were similar, but the risk of myocardial infarction (MI) and repeat revascularization were higher in PCI-treated patients. At 5-year follow-up, the rates of death/stroke/MI are 8.0% lower, and the rate of repeat revascularization is 12.8% lower in CABG-treated patients. In the low SYNTAX score tertile, these trends are not significantly different, but they are in the intermediate and high SYNTAX score subsets. When considering only survival in the 3 tertiles, there was a 0.9%, 6.7%, and 9.0% difference over 5 years, an average of 0.2% to 1.8% per year. Yet, PCI is more often performed in multivessel CAD patients, despite the guidelines and clinical evidence. Can this apparent divergence from the evidence base be supported? Drs. Weintraub and Tcheng and colleagues were asked to defend or critique the current guidelines.

Endothelial dysfunction is known to precede the development of atherosclerosis and results primarily from increased oxidative degradation of NO. We hypothesized that assessment of oxidative stress in the bloodstream will reliably predict endothelial function in healthy adults. A total of 124 healthy nonsmokers had endothelial function assessed using ultrasound measurement of brachial artery flow-mediated vasodilation. Plasma oxidative stress was estimated by measuring the levels of the reduced and oxidized forms of thiols, including glutathione (reduced glutathione and oxidized glutathione) and cysteine (cysteine and cystine), respectively, and the mixed disulfide. Among the traditional risk factors, there were significant and independent correlations between flow-mediated vasodilation and high-density lipoprotein level, body mass index, gender, and the Framingham risk score. Among the thiol markers, plasma cystine (r=−0.23; P=0.009) and the mixed disulfide (r=−0.23; P=0.01) levels correlated with endothelium-dependent but not endothelium-independent vasodilation, even after adjusting for the Framingham risk score and high-sensitivity C-reactive protein level. A higher level of oxidized metabolites was associated with worse endothelial function. In conclusion, the oxidative stress markers, cystine, and the mixed disulfide are independent predictors of endothelial function. These markers, in combination with the Framingham risk score, may help in the early identification of asymptomatic subjects with endothelial dysfunction who are at potentially increased risk for future atherosclerotic disease progression.

Aims To compare the utility of metabolic syndrome (MetS) to random plasma glucose (RPG) in identifying people with diabetes or prediabetes. Methods RPG was measured and an OGTT was performed in 1,155 adults. Test performance was measured by are under the receiver-operating-characteristic curve (AROC). Results Diabetes was found in 5.1% and prediabetes in 20.0%. AROC for MetS with FPG was 0.80 to detect diabetes, and 0.76 for diabetes or prediabetes – similar to RPG (0.82 and 0.72). However, the AROC for MetS excluding fasting plasma glucose (FPG) was lower: 0.69 for diabetes (p<0.01 vs. both RPG and MetS with FPG), and 0.69 for diabetes or prediabetes. AROCs for MetS with FPG and RPG were comparable and higher for recognizing diabetes in blacks vs. whites, and females vs. males. MetS with FPG was superior to RPG for identifying diabetes only in subjects with age <40 or BMI <25. Conclusions MetS features can be used to identify risk of diabetes, but predictive usefulness is driven largely by FPG. Overall, to identify diabetes or prediabetes in blacks and whites with varying age and BMI, MetS is no better than RPG – a more convenient and less expensive test.

Background Psychological responses have been reported for some patients after insertion of an implantable cardioverter defibrillator (ICD). This study tested the effects of a psychoeducational intervention on anxiety, depressive symptoms, functional status and health resource use during the first year after ICD implantation. Methods ICD patients (n=246) were randomized to usual care (UC), group (GRP), or telephone counseling (TC) intervention that included education, symptom management, and coping skill training. Participants were 58 ± 11 years, 73% men, and 23% minorities. Anxiety (STAI), depressive symptoms (BDI-II), and functional status (DASI) were measured at baseline and after 1, 3, 6 & 12 months. Health resource use and disability days were tracked. Analyses were repeated-measures ANCOVA to assess Group X Time effects, Chi-square for percentage with clinically significant anxiety and depression at each time point, and logistic regression. Results All groups experienced decreased anxiety and depressive symptoms over the 12 months; GRP intervention had lower STAI (p=.03) than UC at 3 months. Logistic regression revealed group differences for predicted probability of having depressive symptoms at 12 months (UC=.31, GRP=.17, TC=.13, p=.03). UC had greater calls to providers at 1 and 6 months (p<.05) and more sick/disability days at 12 months (p=.01) than intervention groups. Conclusions A psychoeducational intervention reduced anxiety and depressive symptoms early after ICD, lowered probability of depressive symptoms at one year, and decreased disability days/calls to providers. These findings support further study and clinical use of both group and telephone interventions to yield better psychological outcomes after ICD implant.

Restenosis of a segment of diseased coronary artery following metallic stenting is a common clinical problem and a major limitation of the procedure. Systemic pharmacologic interventions to deal with this problem have met with little success. Several small studies suggest that cilostazol, a phosphodiesterase III inhibitor whose pharmacologic properties include antiplatelet, antithrombotic, and vasodilatory effects; a beneficial effect on serum lipids; and in vitro inhibition of smooth muscle cell proliferation, may help prevent platelet aggregation and impede the accumulation of new intimal tissue in the stented artery. The Cilostazol for RESTenosis (CREST) trial will aim to evaluate more definitively the ability of cilostazol to prevent restenosis following uncomplicated stent implantation for de novo coronary artery stenosis. In this randomized, double-blind, multicenter study, 700 patients will receive clopidogrel, aspirin, and either cilostazol or placebo after successful intracoronary stent implantation. The primary endpoint is minimal luminal diameter (MLD) of the first lesion stented after 6 months; secondary endpoints include MLD in all lesions, mean percent diameter stenosis, target lesion revascularization, and major angiographic endpoints. Safety endpoints are abnormal complete blood count and liver function tests at 1, 3, and 6 months. The trial has been initiated, and enrollment is anticipated to be concluded in 2003. Cilostazol has properties that may reduce or avert in-stent coronary restenosis. The CREST trial is a large, rigorously conducted trial that may corroborate the favorable effects of cilostazol on coronary stent restenosis suggested by earlier studies.

Cilostazol is a phosphodiesterase III inhibitor with pharmacological effects that include vasodilation, inhibition of platelet activation and aggregation, inhibition of thrombosis, increased blood flow to the limbs, improvement in serum lipids with lowering of triglycerides and elevation of high density lipoprotein cholesterol, and inhibition of vascular smooth muscle cell growth. Cilostazol has been shown in multiple randomized clinical trials to result in decreased claudication and improved ability to walk in patients with peripheral arterial disease. In addition, cilostazol has been shown in multiple randomized clinical trials to decrease restenosis in the setting of coronary stent implantation. The purpose of the present paper was to review the vascular effects of cilostazol and to present results of the major clinical trials of the use of cilostazol in peripheral arterial disease and percutaneous coronary intervention with stent implantation.

BACKGROUND Primary care physicians (PCPs) are often expected to screen for melanomas and refer patients with suspicious pigmented lesions to dermatologists. OBJECTIVE To assess whether there is a difference between dermatologists and PCPs in accurately diagnosing melanoma and appropriately managing (based on decisions to refer/biopsy) suspicious pigmented lesions. DESIGN, PARTICIPANTS A survey based on a random sample of 30 photographs of pigmented lesions with known pathology was administered to 101 dermatologists and 115 PCPs from October 2001 to January 2003. MEASUREMENTS Likelihoods that a photographed lesion was melanoma and that the lesion should be biopsied/referred were scored on a 1 to 10 scale. Accuracy of melanoma diagnosis and appropriateness of pigmented lesion management were compared between dermatologists and PCPs by using the areas under (AUC) the receiver operating characteristic (ROC) curves. RESULTS Dermatologists were superior to PCPs in diagnosing melanomas (AUC 0.89 vs 0.80, P < 0.001) and appropriately managing pigmented lesions (AUC. 84 vs 0.76, P < 0.001). PCPs who tended to biopsy lesions themselves did better at managing pigmented lesions than PCPs who did not perform biopsies. Dermatology training during residency did not significantly improve the diagnostic accuracy of PCPs nor their management of pigmented lesions. CONCLUSIONS Dermatologists have both better diagnostic accuracy and ability to manage pigmented lesions than PCPs. Yet, there is a shortage of dermatologists to meet the demand of accurate melanoma screening. More innovative strategies are needed to better train PCPs and enhance skin cancer screening.

OBJECTIVE Age, BMI, and race/ethnicity are used in National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and American Diabetes Association (ADA) guidelines to prompt screening for pre-diabetes and diabetes, but cutoffs have not been evaluated rigorously. RESEARCH DESIGN AND METHODS Random plasma glucose (RPG) was measured and 75-g oral glucose tolerance tests were performed in 1,139 individuals without known diabetes. Screening performance was assessed by logistic regression and area under the receiver operating characteristic curve (AROC). RESULTS NIDDK/ADA indicators age >45 years and BMI >25 kg/m2 provided significant detection of both diabetes and dysglycemia (both AROCs 0.63), but screening was better with continuous-variable models of age, BMI, and race and better still with models of age, BMI, race, sex, and family history (AROC 0.78 and 0.72). However, screening was even better with RPG alone (AROCs 0.81 and 0.72). RPG >125 mg/dl could be used to prompt further evaluation with an OGTT. CONCLUSIONS Use of age, BMI, and race/ethnicity in guidelines for screening to detect diabetes and pre-diabetes may be less important than evaluation of RPG. RPG should be investigated further as a convenient, inexpensive screen with good predictive utility.

Background-In the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial, some patients with stable ischemic heart disease randomized to optimal medical therapy (OMT) crossed over to early revascularization. The predictors and outcomes of patients who crossed over from OMT to revascularization are unknown. Methods and Results-We compared characteristics of OMT patients who did and did not undergo revascularization within 12 months and created a Cox regression model to identify predictors of early revascularization. Patients' health status was measured with the Seattle Angina Questionnaire. To quantify the potential consequences of initiating OMT without percutaneous coronary intervention, we compared the outcomes of crossover patients with a matched cohort randomized to immediate percutaneous coronary intervention. Among 1148 patients randomized to OMT, 185 (16.1%) underwent early revascularization. Patient characteristics independently associated with early revascularization were worse baseline Seattle Angina Questionnaire scores and healthcare system. Among 156 OMT patients undergoing early revascularization matched to 156 patients randomized to percutaneous coronary intervention, rates of mortality (hazard ratio=0.51 [0.13-2.1]) and nonfatal myocardial infarction (hazard ratio=1.9 [0.75-4.6]) were similar, as were 1-year Seattle Angina Questionnaire scores. OMT patients, however, experienced worse health status over the initial year of treatment and more unstable angina admissions (hazard ratio=2.8 [1.1-7.5]). Conclusion-Among COURAGE patients assigned to OMT alone, patients' angina, dissatisfaction with their current treatment, and, to a lesser extent, their health system were associated with early revascularization. Because early crossover was not associated with an increase in irreversible ischemic events or impaired 12-month health status, these findings support an initial trial of OMT in stable ischemic heart disease with close follow-up of the most symptomatic patients.