Lp-PLA2, similar to hsCRP, may also be helpful in predicting ASCVD risk. Moreover, Lp-PLA2 may act synergistically with CRP, further increasing risk when both are elevated. Measurement of Lp-PLA2, which appears to be more specific than hsCRP, may be helpful when it is necessary to further stratify an individual’s risk for ASCVD, especially in the presence of systemic CRP elevations.
Knowing that there is active disease, rather than just risk, may create a greater sense of urgency in patients to become more compliant with treatment recommendations.
The i-plaq Test for Lp-PLA2 is a simple blood test that measures the enzymatic activity of Lp-PLA2 (lipoprotein-associated phospholipase A2), a vascular specific inflammatory marker critical in the formation of rupture-prone plaque.
People with high levels of Lp-PLA2 have active inflammatory disease in the wall of their arteries and increased risk for CVD events independent from other CVD risk factors.
Atherosclerosis causes clinical disease through luminal narrowing or by precipitating thrombi that obstruct blood flow to the heart (coronary heart disease), brain (ischemic stroke), or lower extremities (peripheral vascular disease). The most common of these manifestations is coronary heart disease, including stable angina pectoris and the acute coronary syndromes. Atherosclerosis is a lipoprotein-driven disease that leads to plaque formation at specific sites of the arterial tree through intimal inflammation, necrosis, fibrosis, and calcification.
After decades of indolent progression, such plaques may suddenly cause life-threatening coronary thrombosis presenting as an acute coronary syndrome. Most often, the culprit morphology is plaque rupture with exposure of highly thrombogenic, red cell–rich necrotic core material. The permissive structural requirement for this to occur is an extremely thin fibrous cap, and thus, ruptures occur mainly among lesions defined as thin-cap fibroatheromas. See pictures below.
Lp-PLA2 is produced primarily by macrophages and foam cells in atherosclerotic plaques, it is highly specific for vascular inflammation and not falsely elevated by infections or arthritis, in contrast to hepatic or white blood cell produced inflammatory markers, like hs-CRP.
Once it leaks into the bloodstream it binds to lipoproteins. About 1 in 500 LDL particles have an associated Lp-PLA2 enzyme. When LDL, especially small dense LDL particles, enters the vascular intima, they may oxidize and Lp-PLA2 is the sole enzyme responsible for hydrolyzing the oxidized phospholipids (oxPL).
The products of this hydrolysis, oxidized free fatty acids and lysophosphatidylcholine (lysoPC) trigger an inflammation cascade of adhesion molecule and cytokine expression. This leads to recruitment of more leukocytes to the lesion and a vicious cycle of inflammation. Lp-PLA2 appears to lie in the direct causal pathway of plaque inflammation.
Proposed guidance values for the i-plaq test.
Patients with elevated levels of the i-plaq Test for Lp-PLA2 have active cardiovascular inflammatory disease in their arteries. The Cardiovascular Risk can be reduced with:
No specific preparation is required - no fasting is necessary and patient can be on medication. I-plaq Test results are highly specific for vascular inflammation associated with atherosclerosis and or not likely to be falsely elevated from infections, rheumatology disorders or obesity. Independent from traditional risk factors for CVD like LDL-C and HDL-C and Total Cholesterol
(Source: The Lp-PLA2 Study Collaboration. Lipoprotein-associated phospholipase A2 and risk for coronary disease, stroke, and mortality: collaborative analyses of 32 prospective studies. Lancet. 2010;375:1536-1544)
Patients with the following risk factors should be tested with a comprehensive CVD risk panel including i-plaq Test for Lp-PLA2:
(Source: 1 Sachdeva A, Cannon CP, Deedwania PC et al: for the GTW Steering Committee and Hospitals. Lipid levels in patients hospitalized with coronary artery disease: an analyses of 136,905 hospitalizations in Get With The Guidelines. Am Heart J. 2009;157(1):111-117.e2.)