Circulating Concentrations of the Novel Adipokine Chemerin Are Associated with Cardiovascular Disease Risk in Rheumatoid Arthritis

Abstract

Objective.Depending on physiological context, the adipokine chemerin can reduce or enhance cardiovascular risk. We investigated whether chemerin concentrations represent cardiovascular disease risk in rheumatoid arthritis (RA).Methods.We assessed ELISA-determined chemerin concentrations and those of 4 early endothelial activation molecules as well as angiopoietin 2, which mediates angiogenesis and thereby contributes to advanced atherosclerosis, the common carotid artery intima-media thickness (cIMT), and carotid artery plaque by ultrasound in 236 patients (114 black and 122 white) with RA. Relationships were identified in potential confounder and mediator-adjusted mixed regression models.Results.Mean (SD) chemerin and median (interquartile range) angiopoietin 2 concentrations were 114 (35) ng/ml and 2560 (2044–3341) pg/ml, respectively; the mean (SD) cIMT was 0.708 (0.110) mm, and 40.3% of patients had plaque. Chemerin concentrations were not related to those of early endothelial activation molecules, but associated with those of angiopoietin 2 [β SE = 0.002 (0.0004), p < 0.0001] and plaque [OR 1.006 (95% CI 1.00–1.013), p = 0.05] in all patients. The presence of major conventional cardiovascular risk factors, generalized and abdominal obesity, and RA severity markers modified the independent chemerin-cardiovascular risk relations (interaction p < 0.05). Consequently, chemerin concentrations were associated with cIMT in those with but not without overweight or generalized obesity and abdominal obesity [β SE = 0.001 (0.0003), p = 0.005 and 0.001 (0.0001), p = 0.001 vs −0.001 (0.0004), p = 0.2 and −0.0002 (0.0004), p = 0.6, respectively], and with plaque in those without but not with generalized obesity [OR 1.008 (95% CI) 1.000–1.016, p = 0.03 vs 1.003 (0.990–1.017), p = 0.6, respectively]. The β (SE) for the chemerin-intima-media thickness relations in patients with overweight or generalized obesity and abdominal obesity were larger than in those without these characteristics (p < 0.0001 and = 0.04, respectively).Conclusion.Chemerin is associated with endothelial activation and atherosclerosis in RA. Adiposity influences the chemerin-atherosclerotic phenotype relations in RA.