The invention provides a method of identifying a subject at increased risk of cardiovascular disease (CVD) and/or soft plaque that provides an HDL subpopulation by separating the ApoA-I-containing HDL particles from a plasma sample from the subject, where the HDL particles include an alpha 1-4 (a1-4) subpopulation, a pre-alpha 1-4 (pre-a1-4) subpopulation, and a pre-beta 1-2 (?re-ß1-2) subpopulation, creating an HDL subpopulation profile by quantitating the HDL subpopulations, correlating the HDL subpopulation profile with reference HDL subpopulation profile values and determining whether the subject has an increased risk, a borderline risk, or a low risk for CVD.