Rheumatoid arthritis complicates noninvasive whole blood gene expression testing for coronary artery disease

Abstract

Our objective was to evaluate an age- and sex-specific gene expression score (ASGES) previously validated to detect obstructive coronary artery disease (CAD) in patients with rheumatoid arthritis (RA). We evaluated 20 pairs of nondiabetic coronary patients with and without RA, selected by matching on age, sex, race, body mass index, tobacco use, and number of diseased coronary vessels. Peripheral blood gene expression levels of 23 CAD-associated genes were measured, and a previously validated CAD risk score including age, sex, and gene expression levels (Corus CAD) was computed. Linear regression was used to determine effects of both CAD and RA on the ASGES. Among patients with RA, the ASGES was not associated with CAD. The ASGES was elevated in patients with RA (P<.04) when compared with matched controls. The presence of RA was associated with significantly altered expression for 6 of the 23 genes (P<.05 for all, not adjusted for multiple comparisons): S100 calcium binding protein A12, interleukin-18 receptor accessory protein, caspase 5, S100 calcium binding protein A8, aquaporin 9, and cluster of differentiation 79b. Across a range of coronary artery disease severity, RA was associated with altered expression of CAD-associated genes. Notably, 2 of these genes, S100 calcium binding protein A8 and A12, are associated with neutrophil activation and are under investigation as therapeutic targets for both RA and CAD. These findings highlight common pathogenic mechanisms for RA and CAD and validate the prior exclusion of RA patients from ASGES-based evaluation of CAD likelihood.