Comparison of the Predictive Value of GlycA and Other Biomarkers of Inflammation for Total Death, Incident Cardiovascular Events, Noncardiovascular and Noncancer Inflammatory-Related Events, and Total Cancer Events.

BACKGROUND GlycA is a biomarker that reflects integrated concentrations and glycosylation states of several acute-phase proteins. We studied the association of GlycA and inflammatory biomarkers with future death and disease. METHODS A total of 6523 men and women in the Multi-Ethnic Study of Atherosclerosis who were free of overt cardiovascular disease (CVD) and in generally good health had a baseline blood sample taken. We assayed high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and d-dimer. A spectral deconvolution algorithm was used to quantify GlycA signal amplitudes from automated nuclear magnetic resonance (NMR) LipoProfile® test spectra. Median follow-up was 12.1 years. Among 4 primary outcomes, CVD events were adjudicated, death was by death certificate, and chronic inflammatory-related severe hospitalization and death (ChrIRD) and total cancer were classified using International Classification of Diseases (ICD) codes. We used Poisson regression to study baseline GlycA, hsCRP, IL-6, and d-dimer in relation to total death, CVD, ChrIRD, and total cancer. RESULTS Relative risk per SD of GlycA, IL-6, and d-dimer for total death (n = 915); for total CVD (n = 922); and for ChrIRD (n = 1324) ranged from 1.05 to 1.20, independently of covariates. In contrast, prediction from hsCRP was statistically explained by adjustment for other inflammatory variables. Only GlycA was predictive for total cancer (n = 663). Women had 7% higher values of all inflammatory biomarkers than men and had a significantly lower GlycA prediction coefficient than men in predicting total cancer. CONCLUSIONS The composite biomarker GlycA derived from NMR is associated with risk for total death, CVD, ChrIRD, and total cancer after adjustment for hsCRP, IL-6, and d-dimer. IL-6 and d-dimer contribute information independently of GlycA.

[1]  M. Connelly,et al.  GlycA, a novel marker of inflammation, is elevated in systemic lupus erythematosus , 2016, Lupus.

[2]  Liam G. Fearnley,et al.  The Biomarker GlycA Is Associated with Chronic Inflammation and Predicts Long-Term Risk of Severe Infection. , 2015, Cell systems.

[3]  M. Connelly,et al.  GlycA, a Pro-Inflammatory Glycoprotein Biomarker, and Incident Cardiovascular Disease: Relationship with C-Reactive Protein and Renal Function , 2015, PloS one.

[4]  D. Jacobs,et al.  High-Density Lipoprotein Subclasses and Noncardiovascular, Noncancer Chronic Inflammatory-Related Events Versus Cardiovascular Events: The Multi-Ethnic Study of Atherosclerosis , 2015, Journal of the American Heart Association.

[5]  S. Pinho,et al.  Glycosylation in cancer: mechanisms and clinical implications , 2015, Nature Reviews Cancer.

[6]  R. Mägi,et al.  Cohort Profile Cohort Profile : Estonian Biobank of the Estonian Genome Center , University of Tartu , 2015 .

[7]  D. Greenwood,et al.  Circulating C-Reactive Protein and Breast Cancer Risk—Systematic Literature Review and Meta-analysis of Prospective Cohort Studies , 2015, Cancer Epidemiology, Biomarkers & Prevention.

[8]  P. Ridker,et al.  Novel Protein Glycan Side-Chain Biomarker and Risk of Incident Type 2 Diabetes Mellitus , 2015, Arteriosclerosis, thrombosis, and vascular biology.

[9]  M. Connelly,et al.  Utility of a novel inflammatory marker, GlycA, for assessment of rheumatoid arthritis disease activity and coronary atherosclerosis , 2015, Arthritis Research & Therapy.

[10]  M. Connelly,et al.  GlycA: A Composite Nuclear Magnetic Resonance Biomarker of Systemic Inflammation. , 2015, Clinical chemistry.

[11]  P. Ridker,et al.  A Novel Protein Glycan Biomarker and Future Cardiovascular Disease Events , 2014, Journal of the American Heart Association.

[12]  G. Chrousos,et al.  Circadian rhythmicity, variability and correlation of interleukin-6 levels in plasma and cerebrospinal fluid of healthy men , 2014, Psychoneuroendocrinology.

[13]  D. Duprez,et al.  Severity of Cardiovascular Disease Outcomes Among Patients With HIV Is Related to Markers of Inflammation and Coagulation , 2014, Journal of the American Heart Association.

[14]  Toomas Haller,et al.  Biomarker Profiling by Nuclear Magnetic Resonance Spectroscopy for the Prediction of All-Cause Mortality: An Observational Study of 17,345 Persons , 2014, PLoS medicine.

[15]  Hisashi Adachi,et al.  Inflammation, atherosclerosis, and coronary artery disease. , 2005, The New England journal of medicine.

[16]  J. Gallacher,et al.  C-reactive protein, fibrinogen, and cardiovascular disease prediction. , 2012, The New England journal of medicine.

[17]  L. Newby,et al.  Consultant or Advisory Role: None declared. Stock Ownership: None declared. , 2012 .

[18]  J. Danesh,et al.  Association between C reactive protein and coronary heart disease: mendelian randomisation analysis based on individual participant data , 2011, BMJ : British Medical Journal.

[19]  Markus Perola,et al.  Metabonomic, transcriptomic, and genomic variation of a population cohort , 2010, Molecular systems biology.

[20]  Pauline M Rudd,et al.  A systematic approach to protein glycosylation analysis: a path through the maze. , 2010, Nature chemical biology.

[21]  Veikko Salomaa,et al.  Thirty-five-year trends in cardiovascular risk factors in Finland. , 2010, International journal of epidemiology.

[22]  J. Danesh,et al.  C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis , 2010, The Lancet.

[23]  B. Gersh C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis , 2010 .

[24]  Risto Telama,et al.  Cohort profile: the cardiovascular risk in Young Finns Study. , 2008, International journal of epidemiology.

[25]  Lewis H Kuller,et al.  Inflammatory and Coagulation Biomarkers and Mortality in Patients with HIV Infection , 2008, PLoS medicine.

[26]  C. Delcourt,et al.  Biomarkers of Inflammation and Malnutrition Associated with Early Death in Healthy Elderly People , 2008, Journal of the American Geriatrics Society.

[27]  Vilmundur Gudnason,et al.  Long-Term Interleukin-6 Levels and Subsequent Risk of Coronary Heart Disease: Two New Prospective Studies and a Systematic Review , 2008, PLoS medicine.

[28]  W. Cromwell,et al.  Lipoprotein particle analysis by nuclear magnetic resonance spectroscopy. , 2006, Clinics in laboratory medicine.

[29]  P. Ridker,et al.  High-sensitivity C-reactive protein: clinical importance. , 2004, Current problems in cardiology.

[30]  J. Blacher,et al.  Alpha 1-acid glycoprotein is an independent predictor of in-hospital death in the elderly. , 2003, Age and ageing.

[31]  R. Kronmal,et al.  Multi-Ethnic Study of Atherosclerosis: objectives and design. , 2002, American journal of epidemiology.

[32]  P. Ridker,et al.  C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. , 2000, The New England journal of medicine.

[33]  H. Cohen,et al.  Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly. , 1999, The American journal of medicine.

[34]  A. Levey,et al.  A More Accurate Method To Estimate Glomerular Filtration Rate from Serum Creatinine: A New Prediction Equation , 1999, Annals of Internal Medicine.

[35]  Jimmy D Bell,et al.  Assignment of resonances for ‘acute‐phase’ glycoproteins in high resolution proton NMR spectra of human blood plasma , 1987, FEBS letters.