CLINICAL SIGNIFICANCE OF N-TERMINAL FRAGMENT OF NATRIURETIC PEPTIDE IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS WHO DO NOT RECEIVE PATHOGENETIC THERAPY

Abstract

Objective: to determine the level of the N-terminal fragment of brain natriuretic peptide progenitor (NT-proBNP) in patients with systemic lupus erythematous (SLE) prior to immunosuppressive therapy and its possible association with inflammatory markers, traditional risk factors (TRFs) for cardiovascular diseases (CVD), and transthoracic echocardiographic (EchoCG) parameters.Subjects and methods. The investigation enrolled 28 SLE patients fulfilled the 1997 ACR criteria, including 23 (82%) women (median age, 28.5 [25.0; 32.0] years), who had no clinical signs of CVD and received no immunosuppressive therapy. A control group consisted of 27 age-and sex-matched healthy donors. Disease activity was assessed by SLEDAI-2K; irreversible damages were measured using SLICC. The median duration of SLE was 21.0 [5.0; 60.0] months, the scores of SLEDAI-2K and SLICC/DI were 11 [8; 19] and 0 [0; 0], respectively. The investigators estimated the concentration of Creactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), carried out EchoCG, and assessed TRFs. The serum concentration of NT-proBNP was determined by electrochemiluminescence (Roche Diagnostics, Switzerland). The normal range for NT-proBNP was ≤125.0 pg/ml. Results and discussion. The patients with SLE had elevated levels of NT-proBNP compared with the controls: 160.7 [88.6; 335.4] and 55.2 [36.6; 70.3] pg/ml, respectively (p < 0.001). The patients were divided into two groups: 1) 18 (64%) patients had a NT-proBNP concentration of > 125.0 pg/ml; 2) 10 (36%) patients had no more than this level. As compared with Group 2, Group 1 had the elevated values of IgG anti-cardiolipin (aCL) antibodies (p < 0.01), creatinine (p < 0.05), left ventricular (LV) end-systolic dimension (ESD) (p < 0.05) and decreases in LV ejection fraction (EF) (p < 0.01), glomerular filtration rate (GFR) (p < 0.05), and concentration of anti-Ro antibodies (p < 0.05). In all the patients (n = 5 (18%)) with LV diastolic dysfunction (DD), the NT-proBNP level was much higher than normal; its median was 799.2 [276.6; 1777.0] pg/ml, but no statistically significant differences were found in the frequency of LV DD between the groups (p = 0.066). In the patients with SLE, the NT-proBNP level correlated positively with that of creatinine (r = 0.480; p < 0.01), uric acid (r = 0.427; p < 0.05), IgG aCL (r = 0.710; p < 0.001), anti-double-stranded DNA (anti-dsDNA) antibodies (r = 0.395; p < 0.05), antinuclear antibodies (ANA) (r = 0.256; p < 0.05), LV ESD (r = 0.442; p < 0.05), pulmonary artery systolic pressure (r = 0.486; p < 0.05) and negatively with hemoglobin level (r = -0.493; p < 0.01), C4 complement component (r = -0.475; p < 0.05), GFR (r = -0.58; p < 0.01), and EF (r = -0.505; p < 0.01). The level of NT-proBNP was ascertained to be unassociated with the clinical manifestations of SLE (skin, mucosae, kidneys, nervous system damage, as well as arthritis, serositis, and hematological disorders) and markers of inflammation (CRP, IL-6, TNF-α).Conclusion. The NT-proBNP concentration in the patients with SLE was significantly higher than in the control group (p < 0.001), more than 60% of the untreated SLE patients had elevated NT-proBNP values (>125.0 pg/ml). The higher level of NT-proBNP is associated with the immunological parameters of SLE activity (elevated values of IgG aCL, anti-dsDNA, and ANA as well as C4 hypocomplementemia) and with the markers that reflect deterioration in renal and myocardial functions. There was no relationship of NT-proBNP levels to the clinical manifestations of SLE and the markers of inflammation (CRP, IL-6, and TNF-α) and TRFs.