Provided herein are methods, systems, and compositions for detecting one or more HDL-associated proteins (e.g., ApoC3; ApoC3 and ApoA1; ApoC3 and SAA1/2; or proteins in Biomarker Panels 1-30) in a sample from a subject with, or suspected of having, cardiovascular disease (CVD) or other HDL related disease. In certain embodiments, such methods, systems, and compositions are used to determine the approximate risk of CVD (or other disease) for a subject, and/or the approximate cholesterol efflux capacity (CEC) of a sample.