The invention provides methods of screening a mammalian subject to determine if the subject is at risk to develop or is suffering from, cardiovascular disease. In one embodiment, the method comprises detecting a measurable feature of at least two biomarkers in an HDL subfraction, or in a complex containing apoA-I or apoA-III isolated from a biological sample obtained from the subject, wherein the at least two biomarkers are selected from the group consisting of apoA-I, apoA-II, apoB-100, Lp(a), apoC-I, and apoC-III, combinations or portions and/or derivatives thereof, and comparing the measurable features of the at least two biomarkers from the biological sample to a reference standard, wherein a difference in the measurable features of the at least two biomarkers from the biological sample and the reference standard is indicative of the presence or risk of cardiovascular disease in the subject.