Lipid management: Which test is best for which patient?

Douglas Dawley, M.D.Douglas Dawley, M.D.
Cardiologist, Providence Heart and Vascular Institute

Published February 2013

Management of dyslipidemia, particularly with statins, has significantly reduced major cardiovascular events. Yet half of heart attacks occur in patients with “normal” cholesterol, and more than 30 percent of patients treated with statins in secondary prevention trials have recurrent events within five years.

Why the residual risk? The number of LDL particles (LDL-P), each with Apo B lipoprotein, and not simply the amount of cholesterol in LDL particles (LDL-C), plays a central role in atherosclerosis. LDL particles move into the arterial intima by a gradient-driven process. With increased LDL-P, there is more passive diffusion of these particles into the intima. Once inside the intima, the particles bind to proteoglycans, become oxidized, and are then taken up by monocytes and macrophages to form foam cells and the atherosclerotic plaque.

Cholesterol molecules are mere passengers in the LDL particle, or “car.” By analogy, we know that traffic jams and crowded on-ramps are caused by too many cars on the road, not by the number of passengers in the car. (Humans don’t have HOV lanes!)

Apo B and LDL-P more accurately predict cardiac risk than does LDL-C. For example, when frozen blood samples were analyzed from the Framingham Heart Study, patients in the lowest quartile of LDL-C had 37 percent more cardiovascular events than those in the lowest quartile for LDL-P.

Clinical trials such as VAHIT (Veterans Affairs HDL Intervention Trial) and the Women’s Health Study showed LDL-P to be a better predictor of cardiovascular events than LDL-C. In the recently published MESA trial (Multi-Ethnic Study of Atherosclerosis), LDL-P was predictive of preclinical atherosclerosis, based on carotid intimal-medial thickening, even in subjects with an LDL-C under 100.

Apo B and LDL-P are both measures of LDL particle number. Since they involve different proprietary assays, the decision to measure Apo B or LDL-P is based on factors such as the availability or cost of the test, and clinician preference. My preference is to measure LDL-P by the NMR particle test by LipoScience, which is about $100 and very easy to interpret.

So when do I perform advanced lipid testing? First, I order Lp(a) for patients with premature coronary artery disease, patients who have had heart attacks but no risk factors, or those with a strong family history of coronary artery disease. Lp(a) is a genetically regulated lipoprotein that is elevated in about 10 percent of the population and promotes atherosclerosis. It is not measured by a standard lipid panel, and can be treated with statins and niacin.

Second, in patients at high risk based on the presence of documented vascular disease, diabetes or a strong family history, I initiate therapy based on the standard lipid panel with intended goals of: non-HDL-C under 100, LDL under 70, HDL over 40 and triglycerides under 150.

In about three months I check LDL-P to assess for residual risk and determine if additional therapy is needed. LDL-P treatment goals are set to be equivalent to LDL-C in terms of population percentiles:

LDL-C

Non-HDL

LDL-P

<70

<100      

<700

<100

<130

<1000

<130

<160

<1300


Unrecognized LDL-P elevations are common in patients with “acceptable” LDL-C levels on treatment, and contribute significantly to their residual risk. Statins – HMG Co-A reductase inhibitors that block cholesterol synthesis in the liver – appear to slow LDL-C more than LDL-P. In patients with diabetes and LDL-C under 100, studies have shown that 24 percent still had high LDL-P levels, and 38 percent had borderline-high LDL-P levels.

Methods for lowering LDL-P levels include more aggressive lifestyle changes (diet, exercise and weight loss), niacin, fibrates and fish oil. U.S. Food and Drug Administration-approved fish oils (Lovaza or Vascepa, a new EPA fish oil) at 4 grams per day lower LDL-P by about 10 percent. Higher doses lower LDL-P in a linear manner.

A third group that could benefit from LDL-P as part of their initial evaluation are intermediate-risk patients not on lipid therapy. Often these are women with high LDL-C levels, high HDLs and perhaps other cardiac risk factors. An elevated LDL-P (more than 1100) usually will sway me toward recommending a statin.

Advanced lipid testing to measure LDL-P is helpful in most intermediate- and high-risk patients, but should not routinely be used in low-risk patients. In high-risk patients with diabetes or vascular disease, LDL-P helps to sort out whether their lipid management is adequate or if they have residual risk that might be helped by additional therapy.

LDL-P assessment is inexpensive, does not require fasting and often leads to treatment changes that I believe lower cardiac risk.

Clinical articles by Doug Dawley, M.D.