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

Area of Science:

• Cardiovascular Medicine
• Rheumatology
• Genetics
• Biomarkers

Background:

• An age- and sex-specific gene expression score (ASGES) was previously validated for detecting obstructive coronary artery disease (CAD).
• The study aimed to evaluate the ASGES in patients with rheumatoid arthritis (RA), a condition known to affect cardiovascular health.

Purpose of the Study:

• To assess the utility of a validated age- and sex-specific gene expression score (ASGES) for detecting obstructive coronary artery disease (CAD) in patients with rheumatoid arthritis (RA).
• To investigate the impact of RA on the ASGES and identify specific gene expression alterations associated with both conditions.

Main Methods:

• Evaluated 20 pairs of nondiabetic coronary patients with and without RA, matched for age, sex, race, BMI, tobacco use, and number of diseased coronary vessels.
• Measured peripheral blood gene expression of 23 CAD-associated genes and computed the Corus CAD risk score.
• Employed linear regression to analyze the effects of CAD and RA on the ASGES.

Main Results:

• The ASGES was not associated with CAD in patients with RA.
• The ASGES was significantly elevated in patients with RA compared to matched controls (P<.04).
• RA was associated with significantly altered expression of 6 out of 23 CAD-associated genes (P<.05), including S100A12, IL18RAP, CASP5, S100A8, AQP9, and CD79B.

Conclusions:

• Rheumatoid arthritis is associated with altered expression of CAD-associated genes, impacting the reliability of the ASGES for CAD detection in this population.
• Two genes, S100A8 and S100A12, implicated in neutrophil activation, show altered expression in RA and are potential therapeutic targets for both RA and CAD.
• The findings support the exclusion of RA patients from ASGES-based CAD likelihood evaluations and suggest common pathogenic mechanisms between RA and CAD.