In Case You Missed It: Lp-PLA2 Activity Testing Discussion at AACC
On Wednesday, July 29, more than 100 AACC attendees attended a Breakfast Workshop panel discussion of the emerging science and clinical laboratory testing options related to lipoprotein-associated phospholipase (LP-PLA2) activity.
The discussion was moderated by past president of AACC, Rob Christenson, Ph.D., of the University of Maryland Medical Center, with expert panelists Peter McCullough, M.D., Baylor Health Care System and Baylor University Medical Center, Leslie J. Donato, Ph.D., Mayo Clinic, and Kenneth Blick, Ph.D., The University of Oklahoma College of Medicine.
The first presenter was Dr. McCullough, who began his presentation by setting the stage of where health care is heading and the role of high-quality laboratory testing.
“Personalization of medicine will be the next big leap forward in medicine that will help us customize the care of our patients through better understanding an individual,” said Dr. McCullough. “This personalization will include more use of the laboratory.”
Dr. McCullough provided an overview of the current medical literature including a definition of Lp-PLA2 (PLAC), the clinical application of laboratory testing, and the drugs that lower PLAC.
Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an inflammatory protein produced in the vascular intima and is highly upregulated in atherosclerotic plaques, especially within the necrotic core and macrophages surrounding vulnerable plaques. It circulates bound to low-density lipoproteins and, to a lesser extent, high-density lipoproteins. Patients with higher plaque burden have higher circulating Lp-PLA2.
Individuals with increased Lp-PLA2 (PLAC) activity are at higher risk of coronary heart disease events and stroke. In one population-based study using the REGARDS cohort, individuals with ≥ 225 nmol/min/mL were at increased risk of coronary heart disease (CHD) events.
Recently, elevated Lp-PLA2 activity was found to associate with faster stenosis progression in patients with mild aortic stenosis.
Assessing patient risk of CHD events remains a challenge in primary prevention. In fact, patients with low to moderate CHD risk still have a significant risk of events over 10 years. When assessing CHD risk, cholesterol testing alone is not always enough.
The Benefits of Activity Testing
There are two different approach to testing, measuring the amount of protein or the activity of the enzyme. The bulk of Dr. Donato’s presentation compared the two approaches and outlined why Mayo Clinic choose to implement activity testing.
“The concentration assay utilizing ELISA is a very labor intensive test that cannot be easily offered in house, says Dr. Donato. “In contrast, the activity test leverages an automated chemistry platform that enables you to run it in-house on existing chemistry platforms.”
Dr. Donato referenced a large body of research that showed the benefits and drawbacks of both approaches. In summary, most of these studies show that activity testing is more predictive of future events, while concentration testing was not as predictive.
In addition to the clinical and practical benefits of the activity assay, specimen stability issues associated with the concentration assay raised concerns. Mayo Clinic studies found that concentration samples that were not tested immediately tested could experience 50% falsely elevated levels.
“Our studies found that samples that were tested 3 or 4 days after the sample was drawn, showed up to 50% falsely elevated levels,” says Dr. Donato. “These falsely elevated results can impact the interpretation of the test results and ultimately the treatment approach a physician may take with a patient.”
On the other hand, the Mayo Clinic studies showed that refrigerate and frozen samples are significantly more stable than ambient specimens.
When Should You Order the Test
The new test has been adopted by Mayo Clinic and will soon be part of the standard order set for cardiovascular risk evaluation.
According to Mayo Clinic’s Cardiovascular Laboratory Medicine Group, clinicians should utilize the new activity testing to:
- Identify persons at increased risk for CHD events
- Predict novel risk of CHD in patients with no prior history of cardiovascular events
- Obtain a prognostic value independent of standard lipid profile testing
- For use in conjunction with clinical evaluation and patient risk assessment