Background The very early steps in atherosclerosis comprise adhesion of monocytes to the endothelium and monocyte transmigration through the endothelial barrier into the intima. These processes are effectuated by adhesion molecules and monocyte chemoattractant protein-1 (MCP-1), a molecule that plays a unique and crucial role in early atherosclerosis1,2.
Objectives We examined the impact of cardiovascular risk factors on endothelial activation in patients with rheumatoid arthritis (RA).
Methods We measured circulating soluble E-selectin, vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) concentrations in 217 (black, n=112; white, n=105) patients with RA. Associations were determined in comprehensively adjusted mixed regression models.
Results MCP-1 and ICAM-1 concentrations were lower (390.0±2 versus 487.2±1.7 pg/ml (p=0.02) and 236.5±1.5 versus 308.2±1.4 ng/ml (p=0.0001)) and E-selectin concentrations higher (42.2±19.8 versus 35.5±16.5 ng/ml (p=0.04)) in black compared to white African patients with RA. In all patients, ever smoking, waist circumference, hypertension, diastolic blood pressure, estimated glomerular filtration rate, the number of deformed joints, erythrocyte sedimentation rate, interleukin-6 concentrations and prednisone use were each associated (p=0.05 to <0.01) with endothelial activation (partial R=0.137, -0.166, 0.169, 0.145, -0.205, 0.174, 0.204, 0.168 to 0.423 and 0.165, respectively). Population origin impacted on the low-density lipoprotein cholesterol (LDL-C)- and disease duration-endothelial activation relationships (interaction p<0.05). LDL-C concentrations were associated with ICAM-1 concentrations (partial R=-0.211) in black patients and disease duration with MCP-1 concentrations (partial R=0.278) and an SD (z) score of endothelial activation marker concentrations (partial R=0.243) in white patients. Interleukin-6 concentrations independently explained 18% of the variation in the endothelial activation score.
Conclusions Conventional and non-conventional cardiovascular risk factors consistently impact on atherogenesis in RA. Paradoxically inverse relationships of adiposity and LDL-C concentrations with endothelial activation, as found in this study, are congruent with previous studies in RA in which cardiovascular mortality and events and atherosclerosis were the evaluated outcome measures3-5. The role of interleukin-6 concentrations in optimizing cardiovascular risk stratification in RA deserves further investigation. Atherogenic mechanisms differ by population origin in RA whereas overall cardiovascular risk factor-endothelial activation relationships are mostly similar in black and white Africans with RA.
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Acknowledgements This study was supported by a South African Medical Research Council grant and the National Research Foundation.
Disclosure of Interest None Declared