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Clinical Evidence Supporting the Role of Lp-PLA2 in CHD Risk Assessment |
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Lp-PLA2 (lipoprotein-associated phospholipase A2) is an enzyme specific to the vascular inflammatory process that leads to the formation of vulnerable rupture-prone plaque. Lp-PLA2 breaks down oxidized LDL-C particles, generating two pro-inflammatory and pro-atherogenic byproducts that cause the recruitment of inflammatory cells to the vascular bed.
Recent studies have demonstrated a major role for inflammation in the pathophysiology of vulnerable plaque, and, consequently, of cardiovascular events. Circulating markers of inflammation have attracted considerable interest as predictors of coronary heart disease risk. One such emerging marker is Lp-PLA2, a macrophage-derived enzyme that has been shown to be an independent predictor of coronary events.
Clinical data obtained from recent epidemiological studies suggest that the determination of Lp-PLA2 levels may aid in the identification of individuals at high risk for coronary heart disease (CHD). The PLAC® test is an enzyme immunoassay developed for the quantitative determination of Lp-PLA2 in human serum and plasma, for use in conjunction with clinical evaluation and patient risk assessment in predicting risk for CHD.
The West of Scotland Coronary Prevention Study (WOSCOPS) was a five-year primary prevention trial designed to evaluate the use of pravastatin in 6,595 men with high cholesterol. A total of 580 men who went on to have a myocardial infarction or revascularization (cases) were compared to 1,160 age and smoking matched men who did not have an event (controls). Four inflammatory markers were evaluated as predictors of coronary events. Lp-PLA2 was shown to be the most powerful predictor of the biomarkers that were evaluated. The results showed that those with the highest levels of Lp-PLA2 had twice the risk of an event compared to those individuals with the lowest levels, even after adjustment for traditional risk factors and markers of systemic inflammation. 1
Findings from the Atherosclerosis Risk in Communities (ARIC) Study support the hypothesis that Lp-PLA2 is independently associated with CHD. The ARIC study was a prospective, case-cohort study designed to evaluate atherosclerosis over a period of approximately six years in 12,819 apparently healthy middle-aged men and women. Coronary events were experienced by 608 patients. Mean levels of Lp-PLA2 were higher in patients who had experienced a CHD event compared with those who had not. The results showed that elevated levels of Lp-PLA2 are higher in incident coronary heart disease cases. In individuals with non-elevated LDL levels (<130 mg/dL), elevated Lp-PLA2 levels doubled the risk of a coronary event, even after adjustment for traditional risk factors and C-reactive protein (CRP). 2
The Monitoring Trends and Determinants in Cardiovascular Diseases (MONICA) study had the objective of measuring over 10 years, and in many different populations, the trends in, and determinants of, cardiovascular disease. A subpopulation of the study evaluated the relationship between Lp-PLA2 levels and risk of coronary events. A total of 934 apparently healthy men were followed for 14 years, with 97 men experiencing a coronary event. The study revealed that elevated levels of Lp-PLA2 were predictive of future coronary events in apparently healthy middle-aged men with only moderately elevated total cholesterol. Elevated Lp-PLA2 levels did not correlate with CRP, and were shown to be additive in their ability to predict risk of coronary heart disease. 3
The Mayo Heart Study included 504 patients undergoing clinically indicated coronary angiography by researchers at the Mayo Clinic, and they were followed up for major adverse events. During the four-year follow-up period, 72 major adverse events occurred in 61 of 466 (13%) contacted patients (20 deaths, 14 myocardial infarctions, 28 coronary revascularizations, and 10 strokes). The study evaluated the association of Lp-PLA2 with coronary artery disease (CAD) risk factors and the incidence of major adverse events. The researchers found that higher Lp-PLA2 levels were associated with a significantly greater risk of death, MI, revascularization, or stroke, while nearly 95% of patients with Lp-PLA2 <200 ng/mL were event-free throughout the study.4
In July 2003, The PLAC® test for Lp-PLA2 was cleared by the FDA as an aid in the prediction of CHD risk. The PLAC test is a simple blood test that provides accurate, reliable results to identify patients who are at an elevated risk for a coronary event. Individuals identified at risk by the PLAC test may benefit from more aggressive treatment programs to prevent future cardiac events. The PLAC test is currently available through clinical laboratories nationwide. For more information, please visit www.plactest.com or call 1-877-PLACTEST.
References
1. Packard CJ, O'Reilly DS, Caslake MJ, et al. Lipoprotein-associated phospholipase A2 as an independent predictor of coronary heart disease. West of Scotland Coronary Prevention Study Group. N Engl J Med. 2000;343:1148-1155.
2. Ballantyne CM, Hoogeveen RC, Bang H, et al. Lipoprotein-Associated Phospholipase A2 , High-Sensitivity C-Reactive Protein, and Risk for Incident Coronary Heart Disease in Middle-Aged Men and Women in the Atherosclerosis Risk in Communities (ARIC) Study. Circulation. 2004;109:837-842.
3. Koenig W, Khuseyinova N, Löwel H, Trischler G, Meisinger C. Lipoprotein-Associated Phospholipase A2 Adds to Risk Prediction of Incident Coronary Events by C-Reactive Protein in Apparently Healthy Middle-Aged Men From the General Population: Results From the 14-Year Follow-Up of a Large Cohort From Southern Germany. Circulation. 2004;110:1903-1908.
4. Brilakis ES, McConnell JP, Lennon RJ, Elesber AA, Meyer JG, Perger PB. Association of lipoprotein-associated phospholipase A2 levels with coronary artery disease risk factors, angiographic coronary artery disease, and major adverse events at follow-up. European Heart Journal. 2005;26:137-144.
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