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Importance of Determining Size and Number of Lipoprotein Particles

In the clinical laboratory, we routinely measure the cholesterol content of high-density lipoprotein and low-density lipoprotein particles. We do not measure the apolipoproteins on the particles themselves. Nor do we count or measure the number of particles. Proprietary detergents and reagents are used in assays for HDL-C and LDL-C to separate the lipoproteins from each other, allowing the cholesterol content of specific lipoproteins to be measured individually. For example, HDL-C is commonly measured using a solution of dextran sulfate and magnesium to selectively precipitate HDL from the other lipoproteins present in the sample. Once isolated, the HDL particles are dissolved and the amount of cholesterol in them is determined photometrically using a color-producing enzyme reaction. LDL-C can be measured directly in a similar way or it can be estimated using the HDL-C, triglycerides, and total cholesterol (TC) values. The Friedewald formula is often used to calculate LDL:

LDL-C = TC - (HDL-C)- (Triglycerides/5).

The important point to note here is that traditional LDL-C and HDL-C measurements only tell us how much cholesterol is associated with each lipoprotein particle class. While this is useful information, we now know that this is only part of the story. We have since learned that the number and size of the particles are important as well. The number of LDL particles appears to be more strongly predictive of cardiovascular disease than the LDL-C content, and small dense LDL are known to be more atherogenic than larger, less dense LDL particles.