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LE Magazine November 2008
Reports

Detect Your Risk of Sudden Heart Attack and Stroke

By Laurie Barclay, MD

Advantages of the PLAC® Test

Lp-PLA2 is not influenced by acute illness such as colds and bacterial infections (as occurs with C-reactive protein), and thus serves as a clinically useful biomarker for risk of an acute cardiovascular event. False-positive PLAC® test results may occur in people with high-density lipoprotein (HDL) levels greater than 110 mg/dL, which ordinarily reflects lower cardiovascular risk. This may be attributed to possible genetic differences in individuals with HDL in this range.24

Advantages of the PLAC® Test

Lp-PLA2 has a valuable predictive value—only 5% of even high-risk patients seem to have a recurrent cardiovascular event in the next four to six years when Lp-PLA2 are in the lower ranges. Physicians can thus monitor Lp-PLA2 levels in high-risk patients to figure out when arterial plaque has been stabilized.

A recent study confirms that low levels of Lp-PLA2, in conjunction with other less conventional markers of cardiovascular risk, indicate a very low risk of acute coronary syndrome.25 It should be noted that Lp-PLA2 in an untreated person may rise in time, so a low Lp-PLA2 in apparently healthy people should not be used to assure someone that their lifetime risk is low. Regular monitoring remains important for life-long cardiovascular event prevention.

Although LDL is widely used as a marker of cardiovascular risk, it is far less predictive than Lp-PLA2,26,27 which does not rise until plaque is inflamed and advanced. Only 1 in 500 LDL particles may be associated with Lp-PLA2, and LDL may be elevated for decades before Lp-PLA2 rises, signaling a change from chronic atherosclerosis to acute risk for plaque rupture.

Lipids levels alone provide little information on the status of artery wall health, whereas Lp-PLA2 is a direct measure of it. Rick Lanman, MD, chief medical officer and executive vice president of diaDexus, manufacturer of the PLAC® test, notes, “You can have a patient with coronary-artery bypass graft surgery who has low Lp-PLA2 because they are on a statin and their plaque has become stable.”

What Additional Research is Needed?

Additional answers regarding the value of lowering Lp-PLA2 will be forthcoming when results are announced from the IBIS-2 trial. This large study is looking at the effects of a specific inhibitor of Lp-PLA2 in patients with coronary atherosclerosis. Presently, it is unknown if lowering Lp-PLA2 levels reduces the risk of acute ischemic events.

Investigators from the Mayo Clinic note that Lp-PLA2 levels are independently associated with cardiovascular risk among different populations and across different levels of cholesterol. They argue that this supports the theory that Lp-PLA2 is not just a passive marker of risk, but that it is actively involved in causing atherosclerotic plaque leading to acute heart attack or stroke.6,11

Studies in different populations and careful statistical analysis are needed before concluding that the PLAC® test is useful to predict risk of an acute event in specific individuals. Some studies have suggested that levels of Lp-PLA2 may vary based on gender and race,29,30 suggesting that specific values of risk associated with different levels of Lp-PLA2 may need to be determined for men and women of different races.

A very useful study would look at reductions in cardiovascular events in a group of patients receiving the PLAC® test in addition to traditional evaluation and management of cardiovascular risk, compared with a group of patients managed only with traditional Framingham-based risk assessment.

More studies are needed to know how often the PLAC® test has to be done; how much value needs to be given to this test when used as a marker of the presence and progression of atherosclerosis; and how useful the test is in those who receive various treatments and interventions such as medicines for type 2 diabetes, hypertension and coronary heart disease, and surgery for coronary heart disease.

The consensus panel on the use of Lp-PLA2 testing recommends future studies of the benefits of a drug that inhibits the Lp-PLA2 enzyme; further evaluation of Lp-PLA2 plus other cardiovascular risk markers to better reclassify moderate-risk persons; additional study of Lp-PLA2 in combination with non-invasive imaging tests for better detection of patients at high and low risk; and cost-effectiveness studies.7

PLAC® Test: Sensitive, Reliable, and Non-Invasive

Currently, the PLAC® Test is the only blood test cleared by the US Food and Drug Administration (FDA) to aid in assessing risk for both coronary heart disease and ischemic stroke associated with atherosclerosis. The FDA’s 2005 approval of the Lp-PLA2 blood test16 is based on results from the National Heart Lung and Blood Institute’s Atherosclerosis Risk in Communities (ARIC) study, which involved more than 1,300 patients.28 The groundbreaking ARIC study showed that individuals with high levels of Lp-PLA2 have twice the risk of atherosclerotic stroke over the next six to eight years compared with individuals with normal Lp-PLA2 levels. The study also found that individuals with high levels of both C-reactive protein and Lp-PLA2 had the highest risk for future coronary events and stroke, after adjusting for traditional risk factors.28

Imaging tests typically cost much more than the PLAC® test. Other drawbacks of most imaging tests are that they are time consuming and involve radiation exposure. All that is needed for the PLAC® test is a blood sample. Additionally, the PLAC® test is covered by Medicare and many major commercial insurers. No fasting is needed for the PLAC® test, and the patient can be tested while taking commonly used medications such as aspirin, Tylenol®, Benadryl®, and Pravachol®.

Interpreting PLAC® Test Results

Although the units measuring Lp-PLA2 levels are different from those used to measure total cholesterol, the ranges associated with different levels of risk are similar. Predictive Lp-PLA2 levels for acute cardiovascular events are:

  • Low risk: <200 ng/mL

  • Borderline risk: 200-235 ng/mL

  • High risk: >235 ng/mL.

Levels over 200 or 220 ng/mL are very highly correlated with endothelial dysfunction, which in turn is highly correlated with cardiovascular events and predisposition to atherosclerosis. In practical terms, the PLAC® test can help physicians determine whether someone is at the high end of the low-risk group or at moderate risk. If they have a low Lp-PLA2, less aggressive management strategies may be indicated, while those with a higher level of Lp-PLA2 would more likely need intensive treatment.

Conclusion

Cardiovascular disease prevention is essential for maintaining a long and healthy life span. Yet monitoring risk factors like cholesterol levels and blood pressure has not been enough to predict which individuals are likely to suffer from acute ischemic events.

The PLAC® test offers a reliable, inexpensive, and non-invasive means of determining which individuals are at high risk of suffering from potentially deadly cardiovascular events such as heart attack and stroke. The valuable information garnered from this revolutionary technology can help paint a more accurate picture of an individual’s true risk of succumbing to an ischemic event—allowing physicians and patients to implement aggressive risk management strategies to help avert the tragedy of premature cardiovascular death and disability.

If you have any questions on the scientific content of this article, please call a Life Extension Health Advisor at 1-800-226-2370.

References

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