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BackgroundIn the ISCHEMIA trial (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches), an initial invasive strategy did not significantly reduce rates of cardiovascular events or all-cause mortality in comparison with a conservative strategy in patients with stable ischemic heart disease and moderate/severe myocardial ischemia. The most frequent component of composite cardiovascular end points was myocardial infarction (MI).MethodsISCHEMIA prespecified that the primary and major secondary composite end points of the trial be analyzed using 2 MI definitions. For procedural MI, the primary MI definition used creatine kinase-MB as the preferred biomarker, whereas the secondary definition used cardiac troponin. Procedural thresholds were >5 times the upper reference level for percutaneous coronary intervention and >10 times for coronary artery bypass grafting. Procedural MI definitions included (1) a category of elevated biomarker only events with much higher biomarker thresholds, (2) new ST-segment depression of ≥1 mm for the primary and ≥0.5 mm for the secondary definition, and (3) new coronary dissections >National Heart, Lung, and Blood Institute grade 3. We compared MI type, frequency, and prognosis by treatment assignment using both MI definitions.ResultsProcedural MIs accounted for 20.1% of all MI events with the primary definition and 40.6% of all MI events with the secondary definition. Four-year MI rates in patients undergoing revascularization were more frequent with the invasive versus conservative strategy using the primary (2.7% versus 1.1%; adjusted hazard ratio [HR], 2.98 [95% CI, 1.87-4.73]) and secondary (8.2% versus 2.0%; adjusted HR, 5.04 [95% CI, 3.64-6.97]) MI definitions. Type 1 MIs were less frequent with the invasive versus conservative strategy using the primary (3.40% versus 6.89%; adjusted HR, 0.53 [95% CI, 0.41-0.69]; P

Introduction: Coenzyme Q10 (CoQ10) has been shown to reduce oxidant stress in ischemic heart tissue, though it is unclear whether it alters the expression of anti-oxidant proteins within mitochondria from the ischemic territory. Hypothesis: Using a swine model of chronic myocardial ischemia, we tested whether daily administration of CoQ10for 4-weeks would enhance the expression of key anti-oxidant proteins by TMT proteomics in mitochondria from the chronically ischemic regions. Methods: Twelve pigs underwent placement of a constrictor around the LAD artery and had reduced regional function at 12 weeks. Pigs were given daily dietary supplements of either CoQ10 (10 mg/kg/day) or placebo and studied with 2-D ECHO 4 weeks later. Animals were sacrificed and mitochondria were isolated from the LAD regions, for analysis of PGC1 alpha by western gels and mitochondrial antioxidant proteins by TMT Proteomics. Results: At 12 weeks following instrumentation, regional wall thickening in the LAD region of the Placebo and CoQ10 regions was lower than remote regions (34±7% versus 62±7%; P<0.01), consistent with the presence of chronic myocardial ischemia. Following 4-weeks of treatment, repeat estimates of regional wall thickening in the LAD and Remote regions were 41±5% versus 72±7% (P<0.01), suggesting minimal change in regional function. Post-sacrifice, mitochondria were isolated from the ischemic regions and analyzed for PGC1 alpha and anti-oxidant protein expression. As shown in the Figure, the CoQ10 treated-pigs demonstrated higher levels of PGC1alpha and enhanced anti-oxidant proteins, as measured by TMT proteomics compared with Placebo treated pigs (Significant in yellow). Conclusions: In summary, in this model of chronic myocardial ischemia, supplementation with CoQ10 at 4 weeks improves the expression of anti-oxidant proteins in the mitochondria, potentially by increased PGC1 alpha signaling. [ABSTRACT FROM AUTHOR]