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The Future of Cholesterol Testing?

Content provided by the Faculty of the Harvard Medical School
Excerpted from a Harvard Special Health Report

National Cholesterol Education Program (NCEP) guidelines call for a fasting cholesterol test that measures total cholesterol, HDL cholesterol, LDL cholesterol, and triglyceride levels. If you have metabolic syndrome as well as low to moderate LDL cholesterol, the American Diabetes Association and the American College of Cardiology recommend calculating your non-HDL cholesterol; doing so adds no additional difficulty or expense to a lipid profile.

The fasting lipid profile remains the gold standard test. But as knowledge about cholesterol changes, so do the tests and biomarkers used to measure cardiac risk. For example, testing apolipoproteins (see "Risk factors under investigation") may provide an additional measure of heart disease risk. In the INTERHEART study, researchers found that a test that determined nonfasting apoB/apoA1 ratio was better than any of the standard cholesterol ratios for estimating the risk of heart attack.

Risk factors under investigation

Cholesterol is by no means a perfect indicator of cardiovascular disease risk; in fact, many heart attack victims have normal cholesterol levels, while some people with worrisome lipid test results never suffer heart problems. To better identify who's most at risk, researchers are constantly on the lookout for markers that may provide clues. The following factors are among the most promising candidates for risk factors that tomorrow's doctors may be testing and treating.

Markers of oxidative stress. Oxidants, also known as free radicals, are unstable oxygen molecules that damage cell membranes, proteins, and DNA. This damage is known as oxidative stress. Since 1999, evidence has suggested that biomarkers of oxidative stress may indicate the presence of cardiovascular disease. One example is myeloperoxidase (MPO), an enzyme present in substantial quantities in inflammatory cells such as macrophages. These cells release MPO into the bloodstream in response to inflammation or infection. In addition, several other biomarkers of oxidative stress have been approved for clinical application, and tests have been developed to help clinicians use them to assess cardiovascular risk.

Lipoprotein(a), abbreviated as Lp(a), is a molecule of LDL cholesterol with an extra protein attached. High levels of Lp(a) in the blood have been found to predict cardiovascular disease. Testing Lp(a) is not yet a conventional method of predicting risk of heart disease because no studies have shown that lowering Lp(a) levels—which can be done with niacin—actually reduces the risk of heart disease. New medications in development can also reduce Lp(a) levels, and it is possible that one of these newer drugs may someday be shown to be of therapeutic value. Lp(a) levels vary among different ethnic groups, and standardization of the blood test used to measure the biomarker is needed.

Apolipoprotein B (apoB). This substance is found in many lipid-carrying particles in the blood, including chylomicrons, VLDL, IDL, LDL, and Lp(a). Since each of these particles contains a single apoB molecule, measurements of apoB reflect the total number of such particles. Some studies indicate that the apoB level is a better predictor of death from heart disease than LDL or non-HDL levels. ApoB measurements do not require a fasting blood sample, and the test has been standardized. This test is not widely used in the United States, but some experts are arguing for apoB testing to be done more frequently.

Apolipoprotein M (apoM). This is a protein found mainly in HDL particles. Although its function has yet to be defined, experiments in mice suggest that apoM helps protect against the formation of plaques in the arteries. A study in humans indicated that testing for apoM levels could help identify risk for heart disease. However, more research is needed to verify this finding.

PCSK9. This gene helps control the number of receptors for LDL in the liver. People with an overactive PCSK9 gene have fewer LDL receptors, meaning that the liver doesn't take up as much LDL from the blood. Eliminating the gene increases the liver's LDL receptors, which in turn reduces blood LDL levels. A drug is currently in development that works to block PCSK9, though it is too early to say whether it will make it to the market.

Medical companies are producing and advertising a growing list of patented tests in addition to the standard lipid profile. Such tests are generally more expensive than the standard lipid profile and, as yet, there is not much evidence that they are superior to the standard test in assessing heart disease risk. Still, they may be covered by private insurance and Medicare in some cases.

Last Annual Review Date: 2012-04-01 Copyright: Harvard Health Publications

Reference: Cholesterol section on Better Medicine


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An HDL level less than 40 mg/dL is low and is considered a major risk factor because it increases your risk for developing heart disease.