The landscape of incident disease risk for the biomarker GlycA and its mortality stratification in angiography patients
Scott C. Ritchie,
Pekka J. Karhunen,
Aki S. Havulinna,
Posted 12 Mar 2018
bioRxiv DOI: 10.1101/280677 (published DOI: 10.1161/CIRCGEN.118.002234)
Posted 12 Mar 2018
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.
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