December, 2011

VOL 1 ISSUE 4

CHRONICLES IN CHOLESTEROL
An Insiders Guide to State of The Art Cardiovascular Prevention Laboratory Testing Available From Everest Clinical Laboratories
You may have noticed a new parameter on lipid profile reports lately: non-HDL cholesterol. This calculated result (total cholesterol minus HDL cholesterol) is added in order to draw attention to NCEP recommendations that clinicians aim to reduce levels of non-HDL cholesterol as a secondary lipid-lowering target in patients with elevated serum triglycerides ( 200 mg/dl). Patients with diabetic dyslipidemia and related conditions (metabolic syndrome, central obesity) often have elevated triglycerides, low HDL, and relatively normal calculated LDL values. Relying on LDL targets alone can be misleading in such patients, since they produce highly atherogenic VLDL and IDL lipoproteins as well as small dense atherogenic LDL particles, in spite of the normal LDL values. Consider the following lipid profile in a patient with a recent diagnosis of type 2 diabetes Total cholesterol: 205 mg/dl Triglycerides: 360 mg/dl HDL cholesterol: 35 mg/dl LDL cholesterol: 98 mg/dl. Because this patients LDL level was already at the goal for diabetic patients, continued lifestyle changes were recommended but he was not offered statin therapy. Several years later he sustained an MI, necessitating CABG. Consider what his non-HDL cholesterol level was at the time of the original profile: 170 mg/dl. NCEP ATP III guidelines recommend lowering non-HDL cholesterol as a secondary goal when triglycerides are > 200 mg/dl. The target goals recommended for non-HDL cholesterol are 30 mg/dl above the LDL target for each NCEP Risk Category . In this patient,the LDL goal was < 100 mg/dl, so the secondary target for non-HDL cholesterol was < 130 mg/dl, considerably below his actual non-HDL value of 170 mg/dl. Two factors account for the phenomenon just described. First, the formula for calculating LDL levels increasingly underestimates the true LDL value as triglyceride levels increase. This is why we do 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.

In This Issue: Non-HDL Cholesterol

Non-HDL Cholesterol is a surrogate marker for all the major atherogenic lipoproteins

November, 2011

VOL 1 ISSUE 4

Non-HDL Cholesterol Non-HDL cholesterol may be 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 LDL, VLDL, IDL, and other remnant lipoproteins. 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. LDL can be very misleading when the triglycerides are in the 200-400 mg/dl range.

Sustained hyperglyceridemia leads to elevated levels of VLDL, IDL, and abnormal highly atherogenic LDL particles. Non-HDL cholesterol provides a single index of all these apolipoprotein B-containing lipoproteins, essentially acting as a surrogate for direct apo B determinations. The bottom line is that the measurement of LDL cholesterol alone is not an adequate measure of atherogenic risk in hypertriglyceridemic patients. The cornerstone in the management of non-HDL cholesterol always begins with lifestyle therapy because of the robust reductions in TG levels that may be achieved when combining dietary modification with an exercise regimen. In addition to lifestyle therapy, successful reduction of elevated non-HDL cholesterol may ultimately consist of combination therapy. This would include the use of a statin to serve as the foundation for LDL cholesterol lowering followed by a second therapy to bring non-HDL cholesterol to within the target range. The 3 categories of pharmaceuticals that would fall into this group include omega-3 fatty acid preparations, fibrates, and niacin. Reducing levels of non-HDL cholesterol is becoming an increasingly important target as the incidence of visceral obesity, diabetes mellitus, and the metabolic syndrome continues to escalate in the United States.

By Spencer Kroll MD PhD National Lipid Association Board Certified Board of Directors, Northeast Lipid Association