RT Journal Article SR Electronic T1 The landscape of incident disease risk for the biomarker GlycA and its mortality stratification in angiography patients JF bioRxiv FD Cold Spring Harbor Laboratory SP 280677 DO 10.1101/280677 A1 Johannes Kettunen A1 Scott Ritchie A1 Olga Anufrieva A1 Leo-Pekka Lyytikäinen A1 Jussi Hernesniemi A1 Pekka J. Karhunen A1 Pekka Kuukasjärvi A1 Jari Laurikka A1 Mika Kähönen A1 Terho Lehtimäki A1 Aki S. Havulinna A1 Veikko Salomaa A1 Satu Männistö A1 Mika Ala-Korpela A1 Markus Perola A1 Michael Inouye A1 Peter Würtz YR 2018 UL http://biorxiv.org/content/early/2018/03/12/280677.abstract AB Integration of systems-level biomolecular information with electronic health records has led to the discovery of robust blood-based biomarkers predictive of future health and disease. Of recent intense interest is the GlycA biomarker, a complex nuclear magnetic resonance (NMR) spectroscopy signal reflective of acute and chronic inflammation, which predicts long term risk of diverse outcomes including cardiovascular disease, type 2 diabetes, and all-cause mortality. To systematically explore the specificity of the disease burden indicated by GlycA we analysed the risk for 468 common incident hospitalization and mortality outcomes occurring during an 8-year follow-up of 11,861 adults from Finland. Our analyses of GlycA replicated known associations, identified associations with specific cardiovascular disease outcomes, and uncovered new associations with risk of alcoholic liver disease (meta-analysed hazard ratio 2.94 per 1-SD, P=5×10−6), chronic renal failure (HR=2.47, P=3×10−6), glomerular diseases (HR=1.95, P=1×10−6), chronic obstructive pulmonary disease (HR=1.58, P=3×10−5), inflammatory polyarthropathies (HR=1.46, P=4×10−8), and hypertension (HR=1.21, P=5×10−5). We further evaluated GlycA as a biomarker in secondary prevention of 12-year cardiovascular mortality in 900 angiography patients with suspected coronary artery disease. We observed hazard ratios of 4.87 and 5.00 for 12-year mortality in angiography patients in the fourth and fifth quintiles by GlycA levels demonstrating the prognostic potential of GlycA for identification of high mortality-risk individuals. Both GlycA and C-reactive protein had shared as well as independent contributions to mortality hazard, emphasising the importance of chronic inflammation in secondary prevention of cardiovascular disease.