Inflammatory spectroscopy: Hearty biomarkers
- Published: Apr 15, 2014
- Author: David Bradley
- Channels: NMR Knowledge Base
A research team in the USA has discovered that elevated levels, as identified by nuclear magnetic resonance spectroscopy, of two recently identified proteins in the body can act as markers for inflammation and thus indicators of the presence of cardiovascular disease.
Brent Muhlestein, Jeffrey Anderson and Heidi May at the Intermountain Medical Center Heart Institute in Murray, Utah, have demonstrated that raised concentrations of the proteins GlycA and GlycB act as indicators of inflammation in the body and are correlated with cardiovascular disease. These biomarkers could be used not only in diagnostics and prognosis of heart failure, stroke or premature death but also in biomedical research pointing to new clues about the inflammatory origins of heart disease.
Inflammation is one of the body's standard responses to tissue damage, irritation, or infection, it is intended as part of the natural healing process but pain and discomfort are common side effects. A sprained ankle, a strep throat and auto-immune diseases such as rheumatoid arthritis, are all characterized by inflammation and associated pain, hence the common use of anti-inflammatory agents to mute the symptoms. However, chronic inflammation is also now known to be an important risk factor for heart disease.
NMR spectroscopy can determine levels of GlycA and GlycB in blood samples as part of testing for lipid particles associated with different cholesterol parameters. The spectra reflecting the binding of glucose molecules to a variety of circulating inflammatory proteins, in particular fibrinogen, α1-antichymotrypsin, haptoglobin-1, α1-antitrypsin, complement C3 and α1-acid glycoprotein. Like C-reactive protein, one of the most well-known and studied inflammatory markers shown to be associated with cardiovascular disease, GlycA and GlycB are acute phase proteins with plasma concentrations that increase or decrease in response to changes in the levels of inflammation throughout the body.
"There are at least two benefits evident from this study,” explains Muhlestein, who is lead researcher on the project and co-director of cardiovascular research at the Institute. "First, a new marker of heart attack or stroke may help us to more effectively identify which patients are at risk. Second, now that we know GlycA and GlycB are important predictors of heart disease, we'll seek to understand more about the physiology of these proteins - what causes them to increase and how we can we treat elevated levels."
The new research is among the first to find a connection between cardiovascular disease and raised GlycA and GlycB and was based on a study of almost 3000 patients who had undergone heart catheterization for the assessment of coronary artery disease with a minimum five-year follow-up. Almost half the heart patients had died, suffered a heart attack, stroke, or heart failure during follow-up. Of those the vast majority had significantly higher baseline concentrations of blood plasma GlycA and GlycB. Specifically, the team reports, those with levels in the top 25 percent were more than 30 percent as likely to have had an adverse cardiovascular event when compared to those with levels in the lower 25 percent, even after other risk factors were taken into account.
"The next step will be to determine how GlycA and GlycB correlate with, or are independent of, other common inflammatory markers like C-reactive protein (CRP)," says Muhlestein. "The discovery was not entirely a surprise, given the known involvement of inflammation in atherothrombotic disease, but there are several inflammatory pathways, with different specificities for various diseases, so until we made the connection with GlycA and -B, we were not sure of the connection," he told SpectroscopyNOW. "And, although we already know about the connection with CRP, that connection is non-specific, so CRP elevation can be caused by many other conditions and is quite variable over time. Given that, we are hopeful that GlycA/B will prove to provide incremental prognostic value over CRP and be more specific to vascular disease and, potentially, also a target for treatment."
J Am Coll Cardiol, 2014, 63(12S): "GlycA and GlycB, Novel NMR Biomarkers of Inflammation, Strongly Predict Future Cardiovascular Events, But Not the Presence of Coronary Artery Disease (CAD), Among Patients Undergoing Coronary Angiography: The Intermountain Heart Collaborative Study "
Article by David Bradley
The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.