Non–High-Density Lipoprotein Cholesterol and Guidelines for Cholesterol Lowering in Recent History

Stanley S. Levinson, PhD


Lab Med. 2020;51(1):14-23. 

In This Article

Measurement of LDLC

LDLC is usually measure by calculation, most commonly using the Friedwald equation (LDLC = Total C – HDLC – triglyceride/5; all in mg/dL).[31,32] This measurement is generally made on fasting specimens because triglyceride levels greater than 400 mg per dL may cause unacceptable clinical alterations. Triglyceride-rich VLDL and chylomicrons contain a different ratio of cholesterol to triglycerides than LDL, so that as the chylomicron triglycerides increase, the division by 5 becomes increasingly inaccurate. After a meal, chylomicrons may be substantially increased.

Generally, when the triglycerides level is greater than 400 mg per dL, direct LDL (dLDL) measurement is recommended. Otherwise, calculated LDLC (cLDLC) is preferred because it comes with the routine lipid profile and is as accurate[31,32] for at least 2 reasons. First, different dLDLC commercial methods use different chemicals to inhibit the reaction of cholesterol in beta-lipoproteins other than LDL, so it is unclear that these methods all yield similar results. Second, because of overlap of fractions, separation of beta-lipoproteins from one another by chemical inhibition is very difficult, so that one might not only expect variability between methods but also from lot to lot.[32]

Besides, some of these methods measure the potentially atherogenic lipoprotein Lp(a) but others do not. Lp(a) is always included in the cLDLC concentration. Lp(a) is not affected by the standard cholesterol treatment drugs, namely, statins and ezetimibe. Very high levels of Lp(a) may be atherogenic. Therefore, in a patient with a family history of ASCVD, if a very high cLDLC level is identified that is hardly lowered by these standard drugs, it may be worthwhile to measure the Lp(a).