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Non HDL Cholesterol

Laboratories are adding a new parameter, non-HDL cholesterol (nonHDL-C), to their lipid profiles. Non-HDL-C offers several advantages over LDL cholesterol (LDL-C). A practical advantage is that measurement of non-HDL-C does not require collection of a fasting sample. Laboratories use the Friedewald equation to calculate LDL-C:

LDLC = TotalC − HDLC − Triglycerides/5

This formula increasingly underestimates the true LDL-C value as triglyceride levels increase. This is why the laboratory does not report LDL levels when triglycerides are above 400 mg/dL. But the calculation is affected to some extent at all triglyceride levels above 100 mg/dL. A falsely low LDL-C level may give a patient and their physician a false sense of reassurance.

Patients with diabetic dyslipidemia and related conditions, such as the metabolic syndrome, often have elevated triglycerides, low HDL, and relatively normal calculated LDL values. Sustained hypertriglyceridemia eventuates in elevated levels of very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and small dense atherogenic LDL particles. Non-HDL cholesterol provides a single index of all these apolipoprotein B-containing lipoproteins, essentially acting as a surrogate for direct apolipoprotein B determinations. The bottom line is that the measurement of LDL-C alone is not an adequate measure of atherogenic risk in hypertriglyceridemic patients.

Stated otherwise, non-HDL cholesterol is a stronger predictor of coronary risk than LDL or triglycerides in certain patient populations, since it reflects the sum of serum cholesterol carried by all of the potentially atherogenic lipoproteins including LDL, VLDL, IDL, and other remnant lipoproteins. Moreover, since it is calculated from total cholesterol and HDL cholesterol, both of which are measured directly, it is not affected by the triglyceride level and does not require a fasting specimen.

A recent meta-analysis, which encompassed more than 300,000 patients and 10,000 major adverse events found that calculated LDL cholesterol is no more effective than using the non-HDL cholesterol level to predict the risk of vascular disease (Di Angel­antonio E, et al. JAMA. 2009;302:1993–2000).

NCEP ATP III guidelines recommend lowering non-HDL cholesterol as a secondary goal when triglycerides are > 200 mg/dl. As can be seen in the following table, the target goal for non-HDL is always 30 mg/dl higher than the LDL target for each NCEP Risk Category.

Risk Category

LDL Goal

Non-HDL Goal

CHD & CHD Risk Equivalent

<100 mg/dL

<130 mg/dL

Multiple (2+) Risk Factors

<130 mg/dL

<160 mg/dL

0 – 1 Risk Factor

<160 mg/dL

<190 mg/dL

The concept of good and bad cholesterol is still correct. However, non-HDL cholesterol is becoming the new bad cholesterol.

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