GlycA

Overview:

As an (1) aid in the identification and stratification of individuals at risk for future cardiovascular (CV) disease, (2) independent marker of prognosis for recurrent cardiovascular events in patients with stable coronary disease or acute coronary syndrome, (3) aid in the assessment of disease activity and risk of CV disease in adult Rheumatoid Arthritis (RA) and psoriasis patients, when used in conjunction with standard clinical assessment and for monitoring of anti-inflammatory treatment.

Measurements from EDTA plasma specimens are, on average, 3% to 5% lower than from serum samples. Measurements from NMR LipoTube specimens are, on average, 5% to 6% higher than from serum samples collected in red-top tubes.

GlycA is an indicator for a wide range of disease processes and should not be interpreted without a complete clinical history. Recent medical events resulting in tissue injury, infections, or inflammation, which may cause elevated GlycA levels, should also be considered when interpreting results.

Hemolysis may reduce GlycA concentrations more than 10%.

This test was developed, and its performance characteristics determined, by LabCorp. It has not been cleared or approved by the US Food and Drug Administration (FDA).

The GlycA test quantifies an NMR signal that appears in a region of the NMR LipoProfile® test spectrum separate from that used for lipoprotein particle analysis. Data indicate that this signal is a marker of systemic inflammation, suggesting it may have clinical utility similar or complementary to high sensitivity C-reactive protein (hsCRP), fibrinogen, and other biomarkers of inflammation.1,2

The NMR signal, named "GlycA," originates from the N-acetyl methyl groups of the N-acetylglucosamine moieties on the carbohydrate portions of circulating glycoproteins.1,3 The measured amplitude of this signal reflects the extent of plasma protein glycosylation (not to be confused with nonenzymatic glycation reflecting glucose levels). Most acute phase proteins, released from the liver during an inflammatory response, are glycosylated, and some are glycosylated differentially as a function of inflammation. Acute-phase proteins, such as α1-acid glycoprotein (also known as orosomucoid), haptoglobin, α1-antitrypsin, α1-antichymotrypsin, and transferrin circulate at high enough concentrations to make major contributions to the GlycA signal.1 Therefore, GlycA is hypothesized to be a nonspecific measure of global inflammation status.

Unlike existing biomarkers of inflammation that are discrete molecular species, such as CRP or inflammatory cytokines, GlycA is a composite biomarker that integrates the protein levels and glycosylation states of several of the most abundant acute-phase proteins in serum. This allows for a more stable measure of systemic inflammation with lower intra-individual variability for GlycA than hsCRP.1 While guidelines recommend two serial measurements be taken at least two weeks apart when using hsCRP for CV disease risk assessment, only one measurement is necessary for evaluation of a patient's CV risk using the GlycA test.

1. Otvos JD, Shalaurova I, Wolak-Dinsmore J, et al. GlycA: A Composite Nuclear Magnetic Resonance Biomarker of Systemic Inflammation. Clin Chem. 2015 May;61(5):714-723. PubMed 25779987

2. Akinkuolie AO, Buring JE, Ridker PM, Mora S. A novel protein glycan biomarker and future cardiovascular disease events. J Am Heart Assoc. 2014 Sep 23;3(5):e001221. PubMed 25249300

3. Bell JD, Sadler PJ, Macleod AF, Turner PR, La Ville A. 1H NMR studies of human blood plasma. Assignment of resonances for lipoproteins. FEBS Lett. 1987 Jul 13;219(1):239-243. PubMed 3595877

Akinkuolie AO, Glynn RJ, Ridker PM, Mora S. Protein glycan side-chains, rosuvastatin therapy, and incident vascular events; An analysis from the JUPITER trial. Circulation. 2014;130:A17731.

Bell JD, Brown JC, Nicholson JK, Sadler PJ. Assignment of resonances for 'acute phase' glycoproteins in high resolution proton NMR spectra of human blood plasma. FEBS Lett. 1987 May 11;215(2):311-315. PubMed 2438159

Chung CP, Ormseth MJ, Connelly MA, et al. GlycA, a novel marker of inflammation, is elevated in systemic lupus erythematosus. Lupus. 2016 Mar;25(3):296-300. PubMed 26637290

Dungan K, Binkley P, Osei K. GlycA is a novel marker of inflammation among non-critically ill hospitalized patients with type 2 diabetes. Inflammation. 2015;38(3):1357-1363. PubMed 25586483

Lauridsen MB, Bliddal H, Christensen R, et al. 1H NMR spectroscopy-based interventional metabolic phenotyping: a cohort study of rheumatoid arthritis patients. J Proteome Res. 2010 Sep 3;9(9):4545-4553. PubMed 20701312

Lawler P, Akinkuolie AO, Buring JE, Ridker P, Glynn R, Mora S. A novel biomarker of circulating glycoproteins and cardiovascular and all-cause mortality among 39,521 initially healthy adults. J Am Coll Cardiol. 2015;65(10):A1358.

McGarrah R, Craig D, Haynes C, Dowdy ZE, Shah S, Kraus W. High-density lipoprotein subclass measurements improve mortality risk prediction, discrimination and reclassification in a cardiac catheterization cohort. Artherosclerosis. 2016 Mar;246:229-235 PubMed 26803432

Ormseth MJ, Chung CP, Oeser AM, et al. Utility of a novel inflammatory marker, GlycA, for assessment of rheumatoid arthritis disease activity and coronary atherosclerosis. Arthritis Res Ther. 2015 May 9;17:117. PubMed 25956924