Current methods of stratifying patient risk of myocardial injury and stable angina rely on complex combinations of risk factors that exhibit only limited prognostic power, hence there remains a need to identify biomarkers that can be sampled non-invasively and more accurately predict patient outcomes in the clinic. In the current study, we performed comparative quantitative proteomics on whole plasma sampled from patients with stable angina (NMI), acute myocardial infarction (MI), and healthy control subjects without angina (Ctrl). We detected a total of 371 proteins with high confidence (FDR < 1%, p < 0.05), including 53 candidate biomarkers that displayed ≥ 2-fold modulated expression in patients with cardiovascular diseases (27 associated with atherosclerotic stable angina, 26 with myocardial injury). In the verification phase, we used label-free LC-MRM-MS-based targeted proteomic method to quantify and to verify the candidate biomarkers in pooled plasma, excluded peptides that were poorly distinguished from background, and then performed further validation of the remaining candidates in 49 individual plasma samples. Using this approach, we identified a final panel of 8 proteins that were both reliably and significantly modulated in disease (p < 0.05), including novel biomarkers of atherosclerotic stable angina that have been implicated in endothelial dysfunction (F10 and MST1), and previously unknown biomarkers of myocardial injury reportedly involved in either plaque destabilization (SERPINA3, CPN2, LUM) or tissue protection/repair mechanisms (ORM2, ACTG1, NAGLU). Taken together, our data showed that prognostic markers can be successfully detected in non-depleted human plasma using an iTRAQ/MRM-based discovery-validation approach, and also demonstrate that a novel panel 8 biomarkers can discriminate between the complex pathophysiologies of atherosclerotic stable angina and myocardial injury.