page header image containg i-plaq logo, Doctor image and the words Physician Information

Lp-PLA2 as a predictor of ASCVD Events

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.

Reference: ENDOCRINE PRACTICE Vol 23 (Suppl 2) April 2017

A vascular inflammation marker for rupture-prone plaque

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.

What is the i-plaq Test?

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.

What do the results of the i-plaq Test for Lp-PLA2 mean?

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.

  • The i-plaq Test may be used as a management tool in patients with intermediate to high risk for coronary heart disease or ischemic stroke events. The test results can help to set treatment goals and determine how aggressively the physician should treat risk factors.

  • Tracking the reduction in Lp-PLA2 and LDL-C together in response to therapy is a better indicator of future CVD events than the reduction of LDL-C alone.
    (White HD, et al. J Am heart Assoc. 2013;2:e000360.)

What is Rupture-prone plaque?

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.

illustration showing two artery cross sections - one with stable plaq the other wirth rupture-prone plaque

What is the role of Lp-PLA2 in the plaque rupture process?

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.

Expected values for the i-plaq Test:

i-plaq Test Value Graphic

Proposed guidance values for the i-plaq test.

What can I do to reduce elevated Lp-PLA2 in my patients?

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:

  • Lifestyle changes, more exercise, healthier diet and stop smoking
  • Reduce the intake of added sugar in processed food and losing weight
  • Medication: Lipid lowering medications like statins lower the risk for CVD events lower also Lp-PLA2 and the level of Lp-PLA2 can be used together with LDL-C to monitor the risk of your patients for CVD events.

Lipid Lowering Medications Shown to reduce CV Events, Lower Lp-PLA2 Activity

Bar chart showing lipid- lowering medication shown to reduce CV Events, lower Lp-PLA<sub>2</sub> activity

Tracking the reduction in LDL-C &Lp-PLA2 in response to therapy is a better indicator of furure CDV events than the reduction of LDL-C levels alone (6)

  1. Saougos VG ATVB 2007 Oct;27 (10): 2236-43.
  2. Filipatos TD. Atherosclerosis 2007 Aug;193(2): 248-37
  3. O'Donoghue M. Circulation 2006 Apr 11;113 (14): 17445-52.
  4. Ryu SK. Circulation 20112 Feb;125 (6): 757-66.
  5. Agouridis, AP. Exp. Opin. Pharm. 2011 Dec;12 (17): 2605-11.
  6. White HD, et al. J Am heart Assoc. 2013;2:e000360.

How does the patient prepare for the i-plaq Test?

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)

Who should be tested for CVD risk including i-plaq Test for Lp-PLA2?

Patients with the following risk factors should be tested with a comprehensive CVD risk panel including i-plaq Test for Lp-PLA2:

  • Patients with One or More of the following risks:
    • History of CVD events, including heart attack, bypass, angioplasty or stroke
    • Diabetes (Glucose levels >125 mg/dL or >7.0 mmol/L
    • Chronic Kidney Disease (GFR 60 ml/min/1.73 m2
    • LDL-C ≥ 190 mg/dL or ≥ 4.9 mmol/L
    • Evidence of plaque and or positive CAC Score
    • ≥ 7.5% 10-Year CVD Risk on AHA/ACC Risk Calculator

  • Patients with Three or More of the following risks:
    • Age (Male ≥ 45 years, Female ≥ 55 years)
    • High Total Cholesterol (>240 mg/dL or >6.2 mmol/L)
    • LDL-C between 160-189 mg/dL or 4.1-4.8 mmol/L
    • Low HDL-C (Male < 40 mg/dL or <1.0 mmol/L, Female < 50 mg/dL or <1.3 mmol/L)
    • Cigarette Smoking
    • High Blood Pressure ( ≥ 140/ ≥ 90 Hg)
    • Prescribed Blood Pressure Medication
    • Prediabetes (Glucose 100-125 mg/dL or 5.6 – 6.9 mmol/L)
    • Physical Inactivity
    • Obesity or overweight

Cholesterol tests alone are not enough to determine your patient’s risk for CVD events!

50% Of all heart attacks occur in individuals with normal cholesterol (LDL) levels.

Add the i-plaq Test to your CVD Risk Assessment strategy.

(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.)