Update on the detection and treatment of atherogenic low-density lipoproteins

Abstract

To explain why epidemiological studies have reached such diverse views as to whether apolipoprotein B (apoB) and/or low-density lipoprotein particle number (LDL-P) are more accurate markers of the risk of cardiovascular disease than LDL-C or non-high-density lipoprotein cholesterol (HDL-C) and to review the treatment options to lower LDL. The Emerging Risk Factor Collaboration, a large prospective participant level analysis, a meta-analysis of statin clinical trials, and the Heart Protection Study have each reported that apoB does not add significantly to the cholesterol markers as indices of cardiovascular risk. By contrast, a meta-analysis of published prospective studies demonstrated that non-HDL-C was superior to LDL-C, and apoB was superior to non-HDL-C. As well, three studies using discordance analysis each demonstrated that apoB and LDL-P were superior to the cholesterol markers. Two approaches to resolve these differences are brought to bear in this article: first, which results are credible and second, how does taking the known differences in LDL composition into account, help resolve them. The best identification of individuals at risk of coronary artery disease or with coronary artery disease allows the most efficacious treatment of elevated LDL-P and will permit a more extensive use of some of the more novel LDL-lowering agents. Much of the controversy vanishes once the physiologically driven differences in the composition of the apoB lipoprotein particles are taken into account, illustrating that epidemiology, not directed by physiology, is like shooting without aiming.