Acute myocardial ischemia in the absence of necrosis remains surprisingly difficult to diagnose. Clinicians would benefit from the further availability of simple, objective blood tests to detect ischemia. Proteomics is the quantitative description of protein expression and its changes under biological perturbations. We plan to use proteomic analysis to help identify novel protein markers of myocardial ischemia. These novel markers could be used both to rapidly diagnose myocardial ischemia and to improve the sensitivity and specificity of stress testing without relying on perfusion imaging. The development of novel serum markers of ischemia will occur in two phases. In the identification phase (specific aim #1), we will use proteomic analysis to identify potential novel serum markers of ischemia in patients undergoing stress testing. In the verification phase (specific aim #2), we will determine if associations exist between the levels of these proteins and the severity of myocardial ischemia as graded by perfusion imaging in a larger group of patients undergoing stress testing. Concurrently, we will also determine if associations exist between the levels of existing protein markers and the severity of myocardial ischemia in subjects undergoing stress testing (specific aim #3). To accomplish these objectives, subjects will be enrolled from patients undergoing stress testing with myocardial perfusion imaging. Data will be gathered on their cardiac history, recent symptoms, and the results of their stress test. Blood samples will be collected both before and after the stress test. Proteomic analysis will be performed on the blood samples from an initial subset of patients in order to identify novel proteins that are elevated specifically in the setting of myocardial ischemia. The levels of these novel proteins, as well as of known cardiac markers, will then be determined in the remaining validation cohort of patients. Initial statistical analyses will evaluate the differences in levels of a given protein before and after stress testing and whether that difference varies depending on the severity of ischemia.
