The landscape of incident disease risk for the biomarker GlycA and its mortality stratification in angiography patients

Kettunen, J.; Ritchie, S.; Anufrieva, O.; Lyytikainen, L.-P.; Hernesniemi, J.; Karhunen, P. J.; Kuukasjarvi, P.; Laurikka, J.; Kahonen, M.; Lehtimaki, T.; Havulinna, A. S.; Salomaa, V.; Mannisto, S.; Ala-Korpela, M.; Perola, M.; Inouye, M.; Wyrtz, P.

doi:10.1101/280677

bioRxiv · 10.1101/280677

The landscape of incident disease risk for the biomarker GlycA and its mortality stratification in angiography patients

Kettunen, J.·Ritchie, S.·Anufrieva, O.·Lyytikainen, L.-P.·Hernesniemi, J.·Karhunen, P. J.·Kuukasjarvi, P.·Laurikka, J.·Kahonen, M.·Lehtimaki, T.·Havulinna, A. S.·Salomaa, V.·Mannisto, S.·Ala-Korpela, M.·Perola, M.·Inouye, M.·Wyrtz, P.

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Abstract

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=5x10-6), chronic renal failure (HR=2.47, P=3x10-6), glomerular diseases (HR=1.95, P=1x10-6), chronic obstructive pulmonary disease (HR=1.58, P=3x10-5), inflammatory polyarthropathies (HR=1.46, P=4x10-8), and hypertension (HR=1.21, P=5x10-5). 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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Kettunen, J., Ritchie, S., Anufrieva, O., Lyytikainen, L.-P., Hernesniemi, J., Karhunen, P. J., Kuukasjarvi, P., Laurikka, J., Kahonen, M., Lehtimaki, T., Havulinna, A. S., Salomaa, V., Mannisto, S., Ala-Korpela, M., Perola, M., Inouye, M., Wyrtz, P.. 2018-03-12. The landscape of incident disease risk for the biomarker GlycA and its mortality stratification in angiography patients. https://doi.org/10.1101/280677

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