Utility of Advanced Lipoprotein Testing in Clinical Practice

A standard lipid panel includes total cholesterol, triglycerides, and HDL-C. LDL-C can then be calculated (LDL-C = total cholesterol – HDL-C – TG/5). In some instances, a direct LDL-C assay is employed because once the triglyceride levels are > 400mg/dl a calculated LDL-C is not valid. Non-HDL-C can also be calculated (non-HDL-C = total cholesterol – HDL-C). Increasing levels of LDL-C and non-HDL-C are associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). However, numerous studies have demonstrated that the association of non-HDL-C with ASCVD is more robust. It is possible to measure apolipoprotein B and A-I levels, LDL and HDL size, LDL and HDL particle number, and Lp(a). Numerous studies have documented a link between small dense LDL particles and an increased risk of ASCVD; however, the association is markedly reduced or entirely eliminated when the analyses are adjusted for other factors that affect ASCVD risk. Similarly, there is little data demonstrating that HDL subfractions are useful in risk prediction beyond HDL and other traditional risk factors. Apolipoprotein B levels and LDL particle number are more strongly associated with ASCVD than LDL-C, particularly when the levels of LDL-C and apolipoprotein B levels or LDL particle number are discordant. Similarly, while apolipoprotein B levels or LDL particle number are significantly better than non-HDL-C in predicting ASCVD risk when the levels of non-HDL-C and apolipoprotein B levels or LDL particle number are discordant whether this will alter therapy is debated. The guidelines put forth by a variety of different expert panels and organizations do not require apolipoprotein B or LDL particle number. It is also the author’s opinion that at this time the routine measurement of apolipoprotein B and/or LDL particle number is not required. Until data demonstrate the superiority of measuring apolipoprotein B or LDL particle number on clinical outcomes it is hard to recommend the routine use of such testing. Studies have demonstrated an association of Lp(a) with ASCVD. Many experts recommend measuring Lp(a) in a) patients with unexplained premature CHD, b) patients with a strong family history of premature CHD, c) patients with resistance to LDL lowering with statins, d) patients with rapid unexplained progression of atherosclerosis, and e) patients with familial hypercholesterolemia. Elevations in Lp(a) will stimulate more aggressive lowering of LDL and the consideration of adding drugs that lower Lp(a) such as niacin or PCSK9 inhibitors. While routine use of advanced lipoprotein testing is not recommended it should be recognized that in selected patients the additional information provided can be helpful and result in changes in treatment. As additional drugs to treat lipids are developed and our understanding of lipid and lipoprotein metabolism expands in the future the use of advanced lipoprotein analysis may assume a more important role. For complete coverage of all related areas of Endocrinology, please visit our on-line FREE web-text, WWW.ENDOTEXT.ORG.