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Results: In the meta-analysis, psoas muscle measurements were significantly associated with mortality among men ( p  < 0.05), with high heterogeneity in the associations across all cohorts. There was very little difference in the association between PMA and PMD and mortality (HR 0.83, 95% CI 0.69-0.99, p  = 0.002; HR 0.85, 95% CI 0.77-0.94, p  = 0.041 for one SD increase in PMA and PMD in the random effects model). Combining PMA and PMD into one composite variable by multiplying their values together showed the most robust association in terms of the magnitude of the effect size in men (HR, 0.77; 95% CI 0.73-0.87, p  < 0.001). Indexing PMA to body size did not result in any significant differences in this association. Among women, psoas muscle measurements were not associated with long-term mortality in this meta-analysis., Conclusions: Different psoas muscle measurements were significantly and very similarly associated with mortality among men but not among women. No single measurement stands out, although combining PMA and PMD seems to be a slightly stronger estimate in terms of effect size and should be considered in further studies.

Background: Widespread ST-segment depression with inverted T waves maximally in leads V4-V5 (ie, the global ischemia electrocardiogram [ECG] pattern) is a marker of adverse outcome in patients with non-ST-segment elevation acute coronary syndrome (ACS), perhaps because this pattern is indicative of left main stem stenosis. However, the prognostic value of this ECG pattern has not yet been established., Objective: We studied the predictive value of a prespecified ECG pattern in patients who underwent urgent or emergent coronary artery bypass grafting (CABG)., Methods: We studied the sensitivity, specificity, and predictive values for the global ischemia ECG to predict angiographic left main coronary artery disease. Patients with a 12-lead ECG recorded during anginal symptoms before CABG were included., Results: The global ischemia ECG pattern was found in 61 (76%) of 80 patients with and 12 (19%) of 65 patients without left main disease. The sensitivity, specificity, and positive and negative predictive values for left main coronary artery disease in patients with the global ischemia ECG pattern were 76%, 81%, 84%, and 74%, respectively. In multivariate analysis, the global ischemia ECG pattern was strongly associated with angiographic left main coronary artery disease after adjusting for age, gender, diabetes, hypertension, and smoking (hazard ratio, 16.0; 95% confidence interval, 6.5-39.5; P < 0.001)., Conclusion: The global ischemia ECG pattern was strongly associated with angiographic left main coronary artery disease in patients who underwent urgent or emergent CABG.

Objective: We aimed to characterize the expression of indoleamine 2,3-dioxygenase (IDO) or IDO-induced tryptophan degradation-dependent pathways, which may lead to suppression of T cells and possible protection against atherosclerosis., Methods and Results: Expression of IDO and IDO-related pathway components was analyzed in advanced human atherosclerotic plaques (n = 24) and in non-atherosclerotic arteries (n = 6). Up-regulation of IDO and genes related to the IDO pathway was found to be pronounced in atherosclerotic plaques. Immunohistochemistry demonstrated IDO protein in the atheromatous core and co-distribution with monocyte-macrophages (CD68-positive cells). In gene-set enrichment analysis, the IDO pathway revealed a significant (false discovery rate (FDR) = 0.07) regulatory T cell, fork-head box protein 3 (FoxP3)-initiated CD28-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4)-inducible T cell co-stimulator (ICOS)-driven pathway leading to activation of IDO expression in antigen-presenting cells (APCs). Expression of these IDO pathway genes varied between 2.1- and 16.8-fold as compared to control tissues (P < 0.05 for all)., Conclusions: IDO and the IDO-related pathway are important mediators of the immunoinflammatory responses in advanced atherosclerosis offering new viable therapeutic targets for the development of antiatherogenic immunosuppressive therapies.

Background and Aims: The expression of disintegrin and metalloprotease ADAM-9, ADAM-15, and ADAM-17 has been associated with cell-cell, cell-platelet, and cell-matrix interactions and inflammation. They are possibly implicated in the pathophysiology of atherosclerosis., Methods and Results: Whole-genome expression array and quantitative real-time polymerase chain reaction (PCR) analysis confirmed that ADAM-9, ADAM-15, and ADAM-17 are upregulated in advanced human atherosclerotic lesions in samples from carotid, aortic, and femoral territories compared to samples from internal thoracic artery (ITA) free of atherosclerotic plaques. Western analysis indicated that the majority of these ADAMs were in the catalytically active form. ADAM-9, ADAM-15, and ADAM-17-expressing cells were shown to co-localize with CD68-positive cells of monocytic origin in the atherosclerotic plaques using immunohistochemistry and double-staining immunofluorescence analysis. Co-localization was demonstrated in all vascular territories. In the carotid territory, cells expressing the ADAMs co-distributed also with smooth muscle cells and, in femoral territory, with CD31-positive endothelial cells, indicating that the ADAM expression pattern depends on vascular bed territory., Conclusions: Present findings provide strong evidence for the involvement of catalytically active ADAM-9, ADAM-15, and ADAM-17 in advanced atherosclerosis, most notably associated with cells of monocytic origin.

Objective: Previously, we scanned all 23,000 human genes for differential expression between normal and atherosclerotic tissues and found the involvement of ADAM8., Methods: We investigated the expression of ADAM8 mRNA and protein level in human atherosclerotic tissues and non-atherosclerotic internal thoracic arteries as well as the association of ADAM8 2662 T/G single nucleotide polymorphism (SNP) with the extent of coronary atherosclerosis and with the risk of fatal myocardial infarction., Results: ADAM8 mRNA was up-regulated in carotid, aortic, and femoral atherosclerotic plaques (n=24) when compared with non-atherosclerotic arteries. ADAM8 protein expression was increased in advanced atherosclerotic plaques as compared to control vessels wherein it was localized to macrophages and smooth muscle cells The G allele carriers of the ADAM8 2662 T/G SNP had significantly larger areas of fibrotic, calcified, and complicated plaques in coronary arteries (P=0.027, P=0.011, and P=0.011, respectively) and significantly higher occurrence of myocardial infarction (MI) (P=0.004) and fatal pre-hospital MI (P=0.003) than did the TT homozygotes., Conclusion: ADAM8 is a promising candidate to be involved in atherosclerosis, and its 2662 T/G allelic variant significantly associates with advanced atherosclerotic lesion areas and MI.