Discordance between LDL-C levels and LDL particle number
The size of LDL lipoproteins varies and is dependent on the lipid content they carry inside, which in turn influences the particle density.
LDL cholesterol (LDL-c) refers to the concentration or amount of cholesterol transported by low-density lipoproteins (LDL). LDL particles are the carriers of LDL cholesterol, and within LDL particles, there are differences in both size and density.
Therefore, LDL particles are highly heterogeneous in terms of size and lipid content. Due to this variability in the cholesterol content of LDL particles, the concentration of LDL-C does not accurately reflect the quantity of existing particles (LDL-P), especially in the following situations:
- Family history of atherosclerotic cardiovascular risk
- High triglycerides
- Low levels of HDL cholesterol
- Metabolic syndrome
- Diabetes mellitus
- Recurrent events due to atherosclerotic cardiovascular risk despite lifestyle changes and/or hypolipidemic therapy
Hence, a high number of LDL-P can be associated with normal LDL-C concentrations, indicating an excess of small-sized particles with low cholesterol content but high atherogenic potential. Conversely, a high concentration of LDL-C can coexist with a normal particle number, signifying predominantly cholesterol-rich, larger particles with relatively lower atherogenicity.
This heterogeneity has led to the definition of two phenotypes or patterns associated with higher or lower cardiovascular risk [3], depending on the relationship between LDL-C and LDL-P levels:
- c-LDL > p-LDL, or individuals with particularly large and cholesterol-rich LDL particles (Pattern A).
- c-LDL < p-LDL, or individuals with particularly small and cholesterol-poor LDL particles (Pattern B).
The two aforementioned situations are illustrated in the following figure, adapted from Mora et al.’s work published in Circulation, demonstrating how two individuals with a similar LDL-C concentration may have a higher or lower particle concentration depending on their size.
- E. M. van Leeuwen et al., “A new perspective on lipid research in age-related macular degeneration,” Prog Retin Eye Res, vol. 67, pp. 56–86, Nov. 2018, doi: 10.1016/j.preteyeres.2018.04.
006. - Otvos, J. D. et al. Clinical Implications of Discordance Between LDL Cholesterol and LDL Particle Number. Clin. Lipidol. 5, 105–113 (2011).
- Mora, S. (2009). Advanced lipoprotein testing and subfractionation are not (yet) ready for routine clinical use. Circulation, 119(17), 2396-2404.
- Tehrani, D. M., Zhao, Y., Blaha, M. J., Mora, S., Mackey, R. H., Michos, E. D., … & Wong, N. D. (2016). Discordance of low-density lipoprotein and high-density lipoprotein cholesterol particle versus cholesterol concentration for the prediction of cardiovascular disease in patients with metabolic syndrome and diabetes mellitus (from the Multi-Ethnic Study of Atherosclerosis [MESA]). The American journal of cardiology, 117(12), 1921-1927.
