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Recall that the inflammatory events leading to atherosclerosis are due to the presence of LDL particles which diffuse through the endothelium and into the vessel wall. It makes sense that the more LDL particles there are, the more risk there would be for LDL depositing in the vessel wall. It would seem therefore that measuring the number of LDL particles could be more useful than measuring the cholesterol content of the particles. Traditional measurements of LDL-C quantify the amount of cholesterol associated with all the LDL in a patient sample; they don't tell us how many LDL particles there are. An analogy can be made with battleships. If you wanted to measure the size of a navy that was sailing for your shores, it makes more sense to count the number of ships than to count the amount of cargo the ships carry in order to estimate the number of ships. Of course, it is intuitive that the more LDL-C there is, the greater the number of LDL particles. In that sense, LDL particle number should correlate to LDL cholesterol, and this is indeed true. However, studies now show that measurement of the number of LDL particles is a more powerful predictor of cardiovascular risk. The exact relationship between LDL particle number and cholesterol content actually varies due to the fact that the lipoproteins vary in size and in the ratio of triglycerides to cholesterol. So, although cholesterol is related to LDL particle number, it is not in perfect proportion.How can we then measure LDL particle number? The most obvious way would be to measure apolipoprotein B100 (often abbreviated ApoB). Each LDL particle has one molecule of ApoB attached to it. Therefore, if we measured ApoB, we would be measuring the number of LDL particles, not the contents of those particles, and number appears to be more important with regard to adverse outcomes.

Measuring ApoB and ApoA1 can be performed using standard immunoassay techniques. Nephelometry is popular, as are ELISA-based methods that are performed on automated chemistry analyzer platforms. The power of the ApoB/ApoA1 ratio as a cardiovascular risk marker is getting widespread attention. An individual with seemingly normal LDL-C may in fact have high ApoB concentrations. When this individual has his or her ApoB/ApoA1 ratio calculated, the risk is evident. Studies have also shown that patients with metabolic syndrome and type-2 diabetes can also easily be identified with the ApoB/ApoA1 ratio, whereas these patients cannot always be identified by measuring LDL-C and HDL-C.In 2004, the global INTERHEART study of risk factors for acute myocardial infarction concluded that the ApoB/ApoA1 ratio was the most important risk factor in all geographic regions. The ApoB/ApoA1 ratio is easy to use because the risk is integrated into a single number that indicates the balance between atherogenic and antiatherogenic particles.There have been many studies concerning the predictive power of the ApoB/ApoA1 ratio. One study, which involved thousands of patients who were followed for an average of 10 years, showed that the ApoB/ApoA1 ratio was a strong predictor of stroke in addition to other cardiovascular events. Due to the evidence presented in studies like these, the National Academy of Clinical Biochemistry (NACB) has recommended that the ApoB/ApoA1 ratio be used as an alternative to the usual total cholesterol (TC)/HDL cholesterol ratio when determining lipoprotein-related risk for cardiovascular disease. Some believe that ApoB/ApoA1 testing will eventually replace traditional LDL-C and HDL-C measurements.

Lipoprotein (a) is a modified version of LDL containing a unique protein, apolipoprotein (a). It was discovered in 1963 and is well-associated with vascular disease. Do not confuse apolipoprotein (a) with apolipoprotein A that is found on high density lipoprotein particles. Lipoprotein (a) is abbreviated as Lp(a). Lp(a) is an LDL particle whose ApoB molecule has formed a disulfide bond with another protein called Apo(a), see figure. Apo(a) is a protein very similar in structure to plasminogen. Numerous retrospective case control studies and prospective studies have shown Lp(a) to be an independent risk factor for vascular disease. This means that Lp(a) levels alone (not in conjunction with LDL, or patient risk factors) can predict cardiovascular risk. Lp(a) has been called the most atherogenic lipoprotein. Serum concentrations of Lp(a) are related to genetic factors; drugs and diet changes do not typically lower Lp(a) as they do LDL.