Etiology of acute ischaemic cerebrovascular disease associated with rheumatoid arthritis: changes with progression of anti-inflammatory therapy

BACKGROUND AND PURPOSE: In patients with rheumatoid arthritis (RA), the serum C-reactive protein (CRP) level is associated with ischaemic cerebrovascular disease (iCVD). Acute iCVD patients with RA were investigated, assessing changes of clinical characteristics and CRP with progress in RA treatment. METHODS: Patients hospitalized for acute iCVD from August 2002 to February 2018 were divided into two groups at February 2010. Patients with RA were retrospectively identified. The incidence of RA, the occurrence of acute exacerbation of inflammation due to causes other than synovitis preceding iCVD (non-synovitis AEI) and serum CRP were compared. RESULTS: In the first and second periods, 23/1203 patients (1.9%) and 22/1094 patients (2.0%) respectively had acute iCVD with RA. Non-synovitis AEI was significantly less frequent in the second period (5%, n = 1) than in the first period (35%, n = 8) (P < 0.05). CRP was significantly lower at iCVD onset in the second period [median and interquartile range 2.72 (0.89-4.5) mg/dl vs. 0.34 (0.12-1.19) mg/dl, P < 0.01]. Excluding nine patients with non-synovitis AEI, CRP was still lower in the second period [1.21 (0.47-2.72) mg/dl vs. 0.33 (0.11-0.98) mg/dl, P < 0.01]. CRP levels before both iCVD and non-synovitis AEI tended to be lower in the second period [1.53 (0.3-2.78) mg/dl vs. 0.69 (0.06-1.28) mg/dl, P = 0.059]. Two patients using tocilizumab developed iCVD despite persistently low CRP levels. CONCLUSIONS: With progress in treatment, RA-related inflammation was better suppressed and CRP decreased, but the prevalence of RA amongst acute iCVD patients was unchanged. Strategies for tighter control of inflammation are needed, and a new biomarker may be required in patients using tocilizumab.