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1.
Semin Arthritis Rheum ; 42(4): 333-45, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22920235

ABSTRACT

OBJECTIVE: We assessed whether a serum soluble receptor for advanced glycation end product (sRAGE) levels were associated with a progression of carotid atherosclerosis and arterial stiffness indexes in a cohort of early rheumatoid arthritis (RA) patients. METHODS: RA patients with symptoms onset <2 years were recruited. Vascular assessments and serum sRAGE levels were measured at baseline and 1 year later. Arterial stiffness was determined by pulse wave velocity and aortic augmentation index (AIx). Carotid intima-media thickness was measured using high-resolution ultrasound. RESULTS: Ninety-four patients completed the 1-year study. Fifty-three (56.4%) achieved disease remission [28-joint disease activity score (DAS28 < 2.6)] at 12 months. Improvement in arterial stiffness was observed as reflected by the significant reductions in AIx and pulse wave velocity. At 12 months, the sRAGE levels increased significantly compared with baseline (939.8 ± 517.7 pg/ml to 1272.1 ± 567.3 pg/ml, P < 0.001). Changes in sRAGE levels were significantly higher in men compared to women (768 ± 510 pg/ml versus 271 ± 490 pg/ml, P < 0.05) and was negatively associated with the change in AIx (r = -0.259, P = 0.023). Changes in sRAGE level were not associated with other demographic, clinical, cardiovascular risk factors or treatment. Using multivariate analysis, the change in sRAGE levels and baseline high-density lipoprotein were independent predictors associated with the change in AIx. CONCLUSIONS: Arterial stiffness improved significantly in patients with early RA after effective control of inflammation. Increase in sRAGE level was associated with a decrease in AIx, suggesting that sRAGE may play an important role in the ligand-soluble receptor for advanced glycation end product interaction propagated inflammation and vascular stiffness in these patients.


Subject(s)
Arthritis, Rheumatoid/blood , Atherosclerosis/blood , Carotid Artery Diseases/blood , Receptors, Immunologic/blood , Vascular Stiffness/physiology , Adult , Aged , Antibodies, Monoclonal/therapeutic use , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/drug therapy , Atherosclerosis/complications , Carotid Artery Diseases/complications , Carotid Intima-Media Thickness , Disease Progression , Drug Therapy, Combination , Female , Humans , Infliximab , Male , Methotrexate/therapeutic use , Middle Aged , Prospective Studies , Pulse Wave Analysis , Receptor for Advanced Glycation End Products , Treatment Outcome
2.
J Rheumatol ; 39(12): 2267-75, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22984272

ABSTRACT

OBJECTIVE: To determine the efficacy of methotrexate (MTX) with infliximab (IFX) compared with MTX alone in the prevention of atherosclerosis and arterial stiffness in patients with early rheumatoid arthritis (RA). METHODS: A randomized, open-label study in which early RA patients with active disease were treated with MTX alone (n = 20) and MTX plus IFX (n = 20) for 6 months. Patients were assessed every 3 months. Patients from the MTX-alone group who failed to achieve 28-joint Disease Activity Score remission (DAS28 ≤ 2.6) at 6 months were permitted to escape to open-label IFX. Intima-media thickness (IMT), pulse wave velocity (PWV), and augmentation index (AIx) were measured at baseline, 6 months, and 12 months. RESULTS: At 6 months, there was a significantly greater reduction in PWV in the MTX-alone group (0.18 ± 1.59 m/s) compared with the MTX plus IFX group (-0.78 ± 1.13 m/s; p = 0.044), accompanied by significantly greater reduction in patient's global assessment, number of swollen joints, C-reactive protein, and DAS28 in the MTX plus IFX group compared to the MTX-alone group. The changes in IMT and AIx were similar between the 2 groups. At 12 months, there was a trend favoring early combination treatment with regard to the reduction in PWV (p = 0.06). CONCLUSION: MTX plus IFX causes a more significant reduction in PWV than MTX alone in patients with early RA after 6-month treatment, and further improvement may be achieved in patients who continued on longterm tumor necrosis factor-α blockers, suggesting that early, effective suppression of inflammation may prevent progression of atherosclerosis by improving vascular function.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Atherosclerosis/prevention & control , Methotrexate/therapeutic use , Vascular Stiffness/drug effects , Adult , Arthritis, Rheumatoid/complications , Arthritis, Rheumatoid/physiopathology , Atherosclerosis/diagnosis , Blood Flow Velocity/drug effects , Carotid Intima-Media Thickness , Drug Substitution , Drug Therapy, Combination , Female , Health Status , Humans , Infliximab , Joints/drug effects , Joints/pathology , Joints/physiopathology , Male , Middle Aged , Pulse Wave Analysis , Severity of Illness Index , Treatment Failure , Vascular Stiffness/physiology
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