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Rachel H. Mackey [ email@example.com]
We propose to use stored baseline serum to measure two novel inflammatory biomarkers representing bulk glycosylation of proteins, GlycA, GlycB, LDL and HDL particle concentrations and subclasses, and hsCRP and serum amyloid A (SAA), both acute-phase proteins linked to RA severity, among women with anti-CCP+ RA in WHI-BAA20 who died during follow-up, n=162, and matched anti-CCP+ controls who were alive at follow-up in 2009. We also propose to use NMR metabolomics to obtain, at no additional cost or amount of stored serum, metabolites including TMAO, which has recently been linked to incident CVD and is gut-microbiota-dependent, branched-chain amino acids (BCAA), glutamine/glutamate, and others, to relate to total mortality and to baseline risk factors. Differences in NMR-measured metabolite profile in RA have been reported.1 The women in the proposed study already have measures of anti-CCP, RF, ANA, and a battery of plasma cytokines including IL-6. Deaths will be matched to controls on disease-modifying anti-rheumatic drug (DMARD) use and joint pain severity reported at baseline, since joint pain is independently related to mortality.
Evaluate NMR-spectroscopy measured inflammatory
biomarkers GlycA and GlycB, lipoproteins and lipoprotein subclasses (with a
focus on HDL particles), hsCRP and serum amyloid A (SAA) in relation to death