THE DIRECT-MEASURED LIPID PANEL

THE DIRECT-MEASURED LIPID PANEL

Various guidelines recommend a comprehensive approach to identify patients at risk for cardio-metabolic risk stratification.^5,20,21 Unlike the traditional cholesterol panel, the vertical auto profile (VAP) test is a direct-measured lipid panel. VAP tests are used for comprehensive lipid analysis and simultaneous determination of cholesterol concentration for all five lipoprotein classes and subclasses. The VAP test directly measures LDL. It is also accurate in non-fasting individuals, unlike calculated LDL, which could be low in patients who do not fast as directed prior to testing. Furthermore, the VAP test provides measurements of various lipid components including HDL, TC (VLDL), non-HDL, apolipoprotein B100 (apoB100), Lp(a), IDL, LDL-R, LDL-R subclasses, and remnant lipoproteins such as VLDL3, HDL2 and HDL3.

The VAP test uses single vertical spin, inverted rate zonal, and density gradient ultracentrifugation simultaneously to measure concentrations of cholesterol for all five lipoproteins LDL, VLDL, IDL, HDL, Lp(a), and subclasses. The VAP procedure takes less than one hour to perform and involves the following steps: ultracentrifugation, enzymatic treatment, and software analysis. Ultracentrifugation involves a two-layer density gradient with the bottom layer having a 1:40 serum dilution, followed by centrifugation at 65,000 rpm, which is followed by cholesterol analysis using a continuous flow VAP cholesterol analyzer.

In 1985, the National Cholesterol Education Program (NCEP) was launched by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health. NCEP has put together guidelines for the benefits of lowering cholesterol levels for the prevention of CAD. The NCEP ATP (III) guidelines include the following: 1) measurement of direct LDL; 2) non-HDL and metabolic syndrome (secondary targets of therapy); and 3) emerging risk factors such as Lp(a), small LDL pattern, HDL subclasses, lipoprotein remnants, and apoB. The VAP test complies with NCEP, ATP(III) guidelines.

One advantage of the VAP test is that it measures additional classes of lipoproteins such as Lp(a), IDL, and also subclasses of LDL, HDL (HDL2 and HDL3) and VLDL subclasses (VLDL1,VLDL2,VLDL3). The routine and standard lipid panel testing consists of ordering total cholesterol, LDL, HDL, and triglycerides. By measuring additional lipid parameters, the VAP test can identify patients who are at high risk for CAD and who otherwise would not be identified through routine and standard lipid panel testing.

Various risk assessment tools or models have been developed for cardiovascular disease prevention. Examples of these models include U.S. Framingham risk score (FRS) and the European Systematic Coronary Risk Evaluation (SCORE). Age, gender, total cholesterol, LDL, HDL, smoking, systolic blood pressure, and diabetes are among the factors in the ATP(III) FRS. ATP(III) FRS, however, underestimates the total atherosclerotic vascular disease.

VAP Test:

VAP stands for vertical auto profile, and it tests cholesterol measurements more specifically than previous cholesterol tests. Jere Segrest, a scientist at the University of Alabama in Birmingham, developed the VAP test. In 1999, a company called Atherotech, also located in Birmingham, was formed. Atherotech patented the test and is currently the only company with rights to produce it.

Previous blood cholesterol tests examined the levels of high density lipoproteins (HDL), also called “good cholesterol.” These tests also examined and counted the presence of low density lipoproteins (LDL), or bad cholesterol. These earlier tests were roughly 40% accurate in predicting risk for heart attack.

What scientists discovered while developing the VAP test is that HDL and LDL could be broken down further into subtypes by reclassifying density. These subtypes could further define cholesterol levels and risk of heart attack. High levels of LDL are considered to increase risk for heart attack and necessitate treatment. The VAP test expands on this knowledge. It examines a subtype of LDL called Lp(a), which, when it is the predominant form of LDL, can increase the risk of heart attack up to 25 times.

High levels of HDL were once considered to mean a reduced risk of heart attack. However, HDL is further classed into subtypes, HDL1 and HDL2. While either type of HDL reduces risk, the VAP test measurement separates the two types of HDL. HDL2 is far superior to HDL1, providing more protection for the heart.

The scientists at Atherotech believe that understanding these subtypes can more than double the ability to predict heart attack. Their material has been supported by data from clinical trials at both the University of Alabama and Richmond Medical College. In fact, one aspect of the study at Richmond Medical College, using the VAP test for diagnostics, showed that people with low levels of HDL2 were at a greatly increased risk for abnormally young heart attack.

Most insurance companies recognize studies supporting the VAP test. Virtually all health insurance companies and Medicare pay for it. However, since the test is relatively new, a patient may have to request the VAP instead of the standard cholesterol test.

When a person is uninsured, or has insurance that does not cover the VAP test, it can be ordered online. With shipping and handling, it costs about 100 US dollars (USD). A lab or doctor’s office must administer the test, but it is a simple blood test, much like the previous test for cholesterol. Most labs already have the VAP test on hand, or Atherotech’s website can guide you to a site or doctor that administers the test.

COMPARISON: Standard Lipid profile vs VAP Cholesterol panel

Standard Lipid Profile

*Measures total cholesterol

*Measures HDL

*Calculates LDL using the Friedewald formula (LDL = TC – HDL – TRIG/5)

*Measures triglycerides

*Requires fasting

The VAP Cholesterol Test

*Directly measures total cholesterol

*Directly measures HDL and separates into HDL2 and HDL3 (HDL2 is the “best” cholesterol and when low, is a risk factor for CAD, HDL3 is the least protective HDL)

*Directly measures LDL and separates into 3 components: LDL-R; Lp(a); and IDL (Total LDL may be normal, but one of the 3 components of LDL may be elevated and indicate a risk for CAD. Lp(a) is a genetic risk factor that, when elevated, could indicate a higher risk for heart disease. IDL is also a genetic risk factor.)

*Measures LDL pattern density. (Pattern A indicates large, buoyant LDL particles. Pattern B indicates small, dense LDL particles and is most atherogenic).

*Directly measures triglycerides.

*Directly measures triglyceride-rich lipids: VLDL (1,2,3 and total) (VLDL 3 is small, dense and most dangerous).

*Fasting not required. ATPIII requires expanded lipid test when triglycerides > 400mg/dL and suggests direct measured LDL in non-fasting state.

The following definitions will help you read your VAP Cholesterol Test and understand your lipids and their measurements.

LDL-Cholesterol-Direct a direct measure of your Low Density Lipoprotein cholesterol. LDL is considered to be

your “bad” or “heart disease” cholesterol.

Total HDL-Cholesterol-Direct a direct measure of your High Density Lipoprotein cholesterol. HDL is considered to be the “good” or “protective” type of cholesterol.

Total VLDL-Cholesterol-Direct a direct measure of your Very Low Density Lipoprotein cholesterol, a major carrier of energy rich molecules called “triglycerides;” excess VLDL increases risk for heart disease and diabetes.

SUM Total Cholesterol the sum of your HDL + LDL + VLDL. As a sum total of three diff erent cholesterol measurements, SUM Total Cholesterol alone should not be used to predict the risk of heart disease or stroke.

Triglycerides-Direct a direct measure of energy rich Triglyceride molecules used by the body. Elevated triglycerides are a risk factor which can lead to the formation of “heart disease” lipoproteins.

Total Non-HDL Cholesterol the sum of your LDL + VLDL; the higher the number, the greater the risk of heart disease.

Total apoB100 a measurement of apolipoprotein B100, which helps form, carry and deliver “bad” cholesterol particles to cells. Knowing your apoB100 value greatly increases the VAP’s risk predictive value.

Lp(a) Cholesterol a measurement of “lipoprotein a” cholesterol in your body. A highly inherited risk factor for heart disease, Lp(a) does not respond to traditional LDL-lowering drugs.

IDL Cholesterol a measurement of your Intermediate Density Lipoprotein cholesterol. A strongly inherited risk factor for heart disease, it is elevated in patients with a family history of diabetes.

LDL-R (Real)-C the “Real” cholesterol circulating in your body; it is a component of Total LDL Cholesterol.

Sum Total LDL-C a the sum of Lp(a) + IDL + Real LDL.

Real-LDL Size Pattern refers to LDL cholesterol’s density. A description of type rather than amount of cholesterol, Real-LDL Size Pattern can be A, A/B or B. Pattern A is the safest density, as the human body can rid itself more easily of excess Pattern A LDL. Pattern B LDL carries the highest threat; it is much more susceptible to oxidation (a primary cause of atherosclerosis) and remains in the bloodstream longer than Pattern A LDL. The longer you are exposed to bad cholesterol groups, the greater your risk for disease. Treatments for Pattern B LDL and elevated LDL cholesterol are diff erent, so both measurements must be known for effective treatment. Pattern A/B patients have a mix of both patterns and should work toward a Pattern A LDL value.

Metabolic Syndrome Consider Insulin Resistance/Metabolic Syndrome: If this value is marked as being a risk factor, it is because your profi le indicates the combined presence of Pattern B LDL, low HDL/HDL2 and elevated triglycerides, creating an elevated risk for diabetes due to insulin resistance.

HDL-2 the protective portion of HDL. Low HDL2 is a risk factor for Coronary Artery Disease (CAD), even in patients with normal cholesterol.

HDL-3 important but does not play as great a protective role in protecting against CAD as does HDL-2.

VLDL-3 a triglyceride-rich lipid which can represent an independent risk factor for heart disease.

Lipid testing into the future

Lipid testing has come a long way and continues to evolve further. Analytical methods that are able to test various lipoprotein fractions and subfractions are essential for the detection of various lipid disorders. Measurement with a comprehensive lipid profile that includes specific and sensitive tests helps detect dyslipidemia and associated disorders earlier and more accurately, leading to better management of various cardiovascular disorders. Proper testing is a major factor for stopping the progression of CAD and lowering the burden of disease. Clinical laboratories should consider adding the lipoprotein subfractions discussed here to their future lipid test menu. Physicians should begin ordering such tests and evaluating these parameters.