Objective
Coronary artery disease (CAD) is the leading cause of excess deaths in RA. However, identification of features denoting those with CAD risk is lacking. The composition of circulating mononuclear cell (PBMC) subsets in RA cases differs markedly from healthy controls in extent of T-cell activation with clonal expansion and differentiation to memory effector status and presence of inflammatory monocytes. We sought to evaluate whether elevations in these subpopulations in RA denote those with increased risk for subclinical CAD, as measured by coronary artery calcium (CAC).
Methods
72 RA patients underwent cardiac computed tomography to assess CAC. PBMC subsets were determined by multiparameter flow cytometry. Multivariable logistic regression was used to determine the associations between PBMC subpopulations and presence of CAC.
Results
33% had CAC and exhibited significant increases of circulating CD4 T cell subsets denoting activation and differentiation to memory effector phenotypes. Analogous increases in CD8 T cell subsets, and intermediate CD14hiCD16+monocytes, were also present compared to those without CAC. The CD4 and CD8 T cell subset increases were highly intercorrelated, while increases in CD14hiCD16+monocytes were independent of the elevated CD4 subsets. After adjustment for relevant confounders, levels of CD4+CD56+CD57+ T cells and CD14hiCD16+monocytes remained associated with the presence of CAC.
Conclusions
These PBMC subsets are markers for CAC and suggest mechanisms of atherogenesis in RA may operate in part through their increases, raising further questions about the mechanisms underlying the presence of these subset alterations in RA and the potential for shared etiologic pathways between RA and CVD.