Thus, UA and NSTEMI are closely related conditions whose pathogenesis and clinical presentations are similar but vary in severity. The conditions differ primarily by whether the ischemia is severe enough to cause myocardial damage leading to detectable quantities of myocardial injury biomarkers. The term possible ACS is often assigned during initial evaluation if the ECG is unrevealing and troponin data are not yet available. UA can present without any objective data of myocardial ischemic injury (normal ECG and normal tropo- nin), in which case the initial diagnosis depends solely on the patient s clinical history and the clinician s interpretation and judgment. However, with the increasing sensitivity of troponin assays, biomarker-negative ACS (ie, UA) is becoming rarer.39 The pathogenesis of ACS is considered in the Third Universal Definition of Myocardial Infarction. 21 This statement defines MI caused by a primary coronary artery process such as spon- taneous plaque rupture as MI type 1 and one related to reduced myocardial oxygen supply and/or increased myocardial oxygen demand (in the absence of a direct coronary artery process) as a MI type 2 (Appendix 4, Table A and Section 3.4 for an addi- tional discussion on the diagnosis of MI). 2.2. Epidemiology and Pathogenesis In the United States, the median age at ACS presentation is 68 years (interquartile range 56 to 79), and the male-to-female ratio is approximately 3:2.40 Some patients have a history of stable angina, whereas in others, ACS is the initial presenta- tion of coronary artery disease (CAD). It is estimated that in the United States, each year, >780000 persons will experience an ACS. Approximately 70% of these will have NSTE-ACS.9 Patients with NSTE-ACS typically have more comorbidities, both cardiac and noncardiac, than patients with STEMI. *Estimate includes secondary discharge diagnoses. 