LDL Particle Number

Plasma LDL cholesterol concentration is strongly associated with atherosclerotic cardiovascular risk. Lowering of LDL cholesterol with statin therapy reduces the risk of cardiovascular events. LDL consists of a central core of cholesteryl ester surrounded by a layer of phospholipids and a single molecule of apolipoprotein B-100. LDL particles vary in size, depending on the amount of cholesteryl ester they contain. Small dense LDL particles have much less cholesterol than large, buoyant LDL particles. Even though they contain less cholesterol, small dense LDL particles are believed to be more atherogenic than large buoyant LDL particles. This observation has led to the hypothesis that the overall number of LDL particles may be more predictive of cardiovascular risk than LDL cholesterol concentration.  LDL cholesterol is a measure of the amount of cholesterol being carried in LDL and is not a reliable measure of LDL particle number. 

There are two ways to measure LDL particle numbers. Apolipoprotein B or ApoB measurement is one means of assessing the LDL particle number. Because each LDL particle contains a single molecule of ApoB, measurement of ApoB concentration by nepholometry or immunoturbidimetry is a direct measure of LDL particle number. 95% of all apoB is associated with LDL particles. ApoB assays have been standardized using WHO-IFCC reference materials so it is possible to compare results from different laboratories. Laboratory to laboratory precision ranges from 6-8%.The apoB target is 80 mg/dL. A number of observational studies have reported that apoB concentration is a better predictor of cardiovascular events than LDL cholesterol concentration. The Canadian Cardiovascular Society has added ApoB into their national lipid management guidelines.  

Another more complicated and expensive method to measure LDL particle number is Nuclear Magnetic Resonance Spectroscopy. The NMR signal from the terminal methyl groups of a variety of lipoproteins is proportional to particle count. The NMR Lipoprofile is a proprietary test performed by Liposcience that provides quantitation of size and concentration of LDL particles and various lipid subfractions including VLDL, ID>, LDL and HDL. A number of studies have concluded that the NMR Lipoprofile is a better predictor of cardiovascular events than LDL cholesterol. 

Comparative studies have concluded that both tests are comparable in their ability to predict future cardiovascular risk. Both ApoB and NMR are superior to low density lipoprotein a, non-HDL cholesterol and LDL cholesterol. ApoB is more widely available, easier to perform, and less expensive.

References

Cromwell WC et al. LDL particle number and risk of future cardiovascular disease in the Framingham Offspring Study—Implications for LDL management, J Clin Lipidology, 2007;1(6):583-592.

Allaire J et al. LDL particle number and size and cardiovascular risk: anything new under the sun?. Current Opinion in Lipidology,2017;28(3): 261-266.

Oliveira-Gomes D et al. Apolipoprotein B: Bridging the Gap Between Evidence and Clinical Practice, Circulation,2024;150(1):62-79.

Soffer DE et al. Role of apolipoprotein B in the clinical management of cardiovascular risk in adults: An expert clinical consensus from the national lipid association, J Clin Lipidology 2024;000:1-17.