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In serum, cholesterol is carried primarily on three different lipoproteins—the VLDL, LDL, and HDL molecules. Total cholesterol equals the sum of these three components:
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Most clinical laboratories measure the total cholesterol, the total triglycerides, and the amount of cholesterol found in the HDL fraction, which is easily precipitated from serum. Most triglyceride is found in VLDL particles. Historically, it was estimated that VLDL contained five times as much triglyceride by weight as cholesterol. The amount of cholesterol found in the VLDL fraction could thus be estimated by dividing the triglycerides by 5. Because the triglyceride level is used as a proxy for the amount of VLDL, this estimation formula only applies when the triglyceride level is less than 400 mg/dL (4.52 mmol/L).
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Using these assumptions, the Friedewald equation states that LDL cholesterol can be estimated as:
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When using SI units, the formula becomes
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Modern research has questioned several of the assumptions underlying the Friedewald equation, particularly the assumption that VLDL is always best estimated as triglycerides/5, which is inaccurate when triglycerides are above 150 mg/dL and when LDL cholesterol is less than 70 mg/dL. Therefore, many commercial laboratories have switched to the Martin-Hopkins equation, which uses a flexible factor for deriving VLDL from triglycerides (as opposed to always using 5). The Martin-Hopkins equation reduces the systematic underestimation of LDL cholesterol when triglycerides are greater than 150 mg/dL and LDL is less than 70 mg/dL and is more accurate in estimating LDL from nonfasting blood specimens. There is now also an equation for LDL estimation published by authors affiliated with the National Institutes of Health.
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Understanding the relationships of the different lipid fractions leads to a more accurate understanding of a patient’s lipid-related coronary risk than the total cholesterol. Two persons with the same total cholesterol of 275 mg/dL (7.11 mmol/L) may have very different lipid profiles. One may have an HDL cholesterol of 110 mg/dL (2.84 mmol/L) with a triglyceride of 150 mg/dL (1.69 mmol/L), giving an estimated LDL cholesterol of 135 mg/dL (3.49 mmol/L); the other may have an HDL cholesterol of 25 mg/dL (0.65 mmol/L) with a triglyceride of 200 mg/dL (2.26 mmol/L) and an LDL cholesterol of 210 mg/dL (5.43 mmol/L). The second patient would have more apoprotein B–containing lipoprotein particles, and thus would have much higher CHD risk than the first, assuming no differences in other factors. Thus, evaluation of the lipid fractions is essential before therapy is initiated.
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Non-HDL cholesterol is increasingly recognized as an important measure of the total quantity of apolipoprotein B–containing atherogenic lipid particles. Non-HDL cholesterol is calculated as: total cholesterol – HDL cholesterol. Advantages of calculating non-HDL cholesterol are that it is directly measured, requires no additional cost, is less sensitive to fasting status, and is a better predictor of cardiovascular risk compared to LDL cholesterol.
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Lipoprotein(a), a subfraction of LDL ...