Left ventricular function in treatment-naive early rheumatoid arthritis

The role of inflammation and anti-cyclic citrullinated peptide antibodies (anti-CCP) in the pathogenesis of cardiovascular disease in early rheumatoid arthritis (RA) remains unclear. Previous studies have suggested that both disease activity and disease duration are associated with atherosclerosis and a higher mortality rate caused primarily by coronary artery disease.

We investigated how disease activity, anti-CCP status and coronary calcium score in treatment-naive early RA impacts left ventricular (LV) systolic function.

Fifty-tree patients (30 women) with mean age 58.3±1.3 years and steroid- and disease-modifying antirheumatic drug (DMARD)-naive early RA were included. Disease activity was scored by the use of the Danish national DANBIO registry (number of swollen joints (NSJ (28)), number of tender joints (NTJ (28)), C-reactive protein (CRP) and Health Assessment Questionnaire (HAQ)). Pain, fatigue, patient and physician global assessment and a composite disease activity score (DAS28-CRP) were assessed by visual analog scales (VAS) 0-100. IgM rheumafactor (IgM-RF) and anti-CCP titers were evaluated by standardized techniques. Coronary calcium score was estimated by computed tomography by calculating the Agaston score. One experienced senior rheumatologist and one experienced cardiologist performed all the clinical assessments as well as all the transthoracic echocardiography (TTE) and coronary CT analysis.

Disease activity scores before treatment at baseline were: NSJ (28) 7.1±2.7, NTJ (28) 8.5±3.5, CRP 11.7±12.9 mmol/l, HAQ 0.71±0.6, pain VAS 51.1±23.7, fatigue VAS 49.3±24.9, physician global assessment 54.2±15.0 and DAS28-CRP 4.8±0.7. Twenty-three (43%) patients were IgM-RF positive and 33 (62%) were anti-CCP positive. We found LV systolic function by conventional ejection fraction (EF) to be 54.1±9.2% and to be non-significant correlated to disease activity (CRP: r=0.07, p=0.64; baseline NSJ: r=-0.13, p=0.33; NTJ: r=-0.08, p=0.58; HAQ: r=0.23, p=0.1; pain VAS: r=-0.05, p=0.74; fatigue VAS: r=0.03, p=0,83; physician global assessment: r=-0.09, p=0.54 and DAS28: r=-0.03, p=0.84). However, using a more sensitive measurement of the LV function by global longitudinal systolic strain (GLS), we found a significant correlation: HAQ (r=0.29; p=0.037), patient global assessment by VAS (r=0.35; p=0.011), patient fatigue assessment by VAS (r=0.3; p=0.03) and DAS28-CRP (r=0.28; p=0.043); all corrected for relevant confounders (age, gender, pulse and blood pressure). Furthermore, anti-CCP was highly significantly correlated with GLS (r=-0.44; p=0.001) in univariate analysis. In multivariate analysis, it still remained significantly correlated (p=0.018), after correction for age, gender, pulse, and blood pressure. Using strain analysis of LV function, we found a significant difference in GLS in patients with high values of anti-CCP (titers ≥340) compared to patients with anti-CCP (titers <340); (-19.9±2.1% vs. -16.4±2.8%; p=0.0001). For patients with high IgM-RF, results were non-significant.

We observed a significant correlation between increased disease activity and cardiac function in treatment-naive early RA.