Discordance between lipoprotein particle number and cholesterol content: an update

The cholesterol content within atherogenic apolipoprotein-B (apoB) containing lipid particles is the center of consensus guidelines and clinicians' focus whenever evaluating a patient's risk for atherosclerotic cardiovascular disease. The pathobiology of atherosclerosis requires the retention of lipoprotein particles within the vascular intima over time followed by maladaptive inflammation resulting in plaque formation and rupture in some. The cholesterol content is widely variable within each particle creating either cholesterol-deplete or cholesterol-enriched particles. This variance in particle cholesterol content varies within and between individuals. Discordance analysis exploits this difference in cholesterol content of particles to demonstrate the differential significance of LDL-cholesterol (LDL-C) and non-HDL-C from measures of lipoprotein particle number in terms of assessing atherosclerotic cardiovascular disease risks.

Three studies have added to the growing body of literature of discordance analysis. Despite wide variability of discordance cutoffs, baseline risk of atherosclerotic disease, and populations sampled, the conclusion remains the same: risk of atherosclerotic disease follows apoB lipid particle concentration rather than cholesterol content of lipid particles.

In addition to traditional lipid fractions, assessments of atherogenic particle number should be strongly considered whenever assessing CVD risk in nontreated and treated individuals. There is a need for clinical trials that focus not only on the reduction in LDL-C but apoB, as well.