Relationship between pro-inflammatory cytokines and subclinical myocardial dysfunction in patients with rheumatoid arthritis

Objective: to investigate the association of pro-inflammatory cytokines, including interleukin (IL)-6, tumor necrosis factor α (TNFα), IL-1 receptor antagonist (IL-1Ra), with subclinical left ventricular (LV) dysfunction in patients with rheumatoid arthritis (RA).

Material and methods. The study included 61 patients with RA who met the 2010 ACR/EULAR (American College of Rheumatology / European Alliance of Associations for Rheumatology) criteria. In this group, 80% were women, mean age was 47.8±10.1 years, and the median disease duration before initiation of biologics was 120 [54; 165] months. All patients underwent determination of serum N-terminal pro-brain natriuretic peptide (NT-proBNP), IL-6, TNFα, IL-1Ra levels, and echocardiography with assessment of global longitudinal myocardial deformation (GLSLV) of the LV using speckle-tracking.

Results and discussion. In patients with RA, IL-6 and TNFα levels were significantly higher than in controls. In RA patients with subclinical myocardial dysfunction, IL-6 levels were significantly higher than in patients with preserved myocardial function (median 14.7 [0.76; 38.5] and 7.8 [0.11; 17.5] pg/ml, respectively; p<0.05). TNFα and IL-1Ra levels did not differ significantly between these groups. RA patients were divided into four groups. Group 1 included patients with elevation of all three cytokines (n=9), group 2 – of two cytokines (n=19), group 3 – of one cytokine (n=23), and group 4 (n=10) had normal cytokine levels. ESR, DAS28 (Disease Activity Score 28), and CRP levels in groups 1–3 were higher than in group 4. All groups differed significantly in ejection fraction (EF) and LV lateral mitral annular velocity (E’). GLSLV was significantly lower in group 1 than in group 4. IL-6 level correlated with GLSLV (r=-0.4); IL-1Ra level– with EF (r=-0.5), LV E’ (r=-0.4), and the ratio of early transmitral flow velocity (E)/E’ (r=0.3); TNFα level – with LV E’ (r=-0.3), p<0.05 for all comparisons.

Conclusion. In RA patients with myocardial dysfunction, IL-6 levels are significantly elevated. Simultaneous elevation of IL-6, IL-1Ra, and TNFα leads to more pronounced impairment of systolic and diastolic myocardial function. Inflammation in RA contributes to the deterioration of cardiac myocardial function.

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