Iwona Brzosko

Cardiac Arrhythmias and Conduction Disturbances in Patients With Ankylosing Spondylitis

Conduction disturbances, aortic incompetence, and myocardial fibrosis are known complications in adult patients with ankylosing spondylitis (AS). Its incidence has been reported to be 10% to 30%; however, less attention has been paid to all cardiac arrhythmias. The aim of this study was to evaluate arrhythmias and conduction disturbances in patients with AS using electrocardiograms and Holter monitoring (including heart rate variability analysis) and to estimate its relationships with age, gender, clinical features, and duration of AS. Thirty-one patients with AS (20 to 69 years old, mean 50 ± 14) and 22 healthy volunteers (26 to 69 years old, mean 49 ± 13) underwent rheumatologic and cardiologic evaluations. Ventricular extrasystoles were present in 55% of AS patients and in 28% of controls. Supraventricular extrasystoles were present in 94% of AS patients and 100% of controls. The frequency of ventricular extrasystoles was found to be higher in the AS patients than in the control subjects. Significant differences were found in heart rate variability analyses: ultra low-frequency power and root mean square recessive difference (r-MSSD) were lower in the AS group. When the AS group was divided into subgroups (stages 3 and 4), significant differences were found between control subjects and stage 3 patients in PR interval, heart rate (HR), T-wave duration, ultra low frequency, and r-MSSD and between controls and stage 4 patients in HR, T-wave duration, and r-MSSD. QTc and QTd were not significantly different in groups and subgroups and were not correlated with any other clinical or electrocardiographic parameter. Cardiac arrhythmias were more frequent in patients with AS than in the healthy population. Simple electrocardiograms and Holter parameters do not correlate with the incidence of VESs, age, gender, clinical features, and duration of AS.

Therapy with infliximab decreases the CD4+CD28- T cell compartment in peripheral blood in patients with rheumatoid arthritis

Chronic inflammatory syndromes such as rheumatoid arthritis (RA) are associated with high frequencies of CD4+CD28− T cells. The number of these cells is genetically determined and may also be a consequence of chronic exposure to tumor necrosis factor-alpha (TNFα). The aim of this study was to examine whether the reported efficacy of anti-TNFα therapy in RA involves a resurgence of T cell populations that re-express CD28. After 36-week therapy with infliximab, a significant decrease in CD4+CD28− T cells in RA patients was observed in comparison with baseline. The results suggest that TNFα-neutralizing therapy may restore T cell homeostasis and reduce expansion of the CD28− T cells, which are cytotoxic and may contribute to organ manifestations in RA.

The urinary excretion of pyridinoline and deoxypyridinoline during rheumatoid arthritis therapy with infliximab

Rheumatoid arthritis is a systemic disease that causes inflammation and joint destruction. As a result of pathological destruction in bone and cartilage, crosslinks in collagen are resorbed more rapidly. This causes a rise in circulating collagen crosslink levels and their urinary excretion. In RA, apart from the crosslink resorption at the site of inflamed joints, there may be increased resorption due to general bone loss associated with disease activity. The aim of this study was to evaluate the influence of therapy with infliximab on urinary excretion of pyridinoline (PYD) and deoxypyridinoline (DPYR) as a markers of collagen degradation and its correlation with clinical and biochemical parameters of disease activity. Seventeen patients with active rheumatoid arthritis treated with infliximab were recruited into the study. The therapy resulted in the reduction in the symptoms of RA and urinary excretion of PYD and DPYR. The urinary excretion of PYD correlated with a number of swollen joints, morning stiffness, CRP and ESR. The urinary excretion of DPYR correlated during infliximab therapy with the number of swollen and tender joints and morning stiffness. The measurement of urinary excretion of PYR and DPYR may give insight into bone metabolism and help us to better understand the actual changes in bone and cartilage caused by RA and its treatment.

Coronary stenosis treated by percutaneous angioplasty in a patient with dermatomyositis.

A female patient suffering from dermatomyositis in whom symptoms of heart failure without angina is described. An impairment of left ventricular function and significant coronary lesions were diagnosed using noninvasive and invasive procedures. Coronary angioplasty with stent implantation was successfully applied to improve the quality of life and clinical symptoms.

03.03 Serum interleukin 23 in polish patients with systemic lupus erythematosus – association with obesity and peripheral vascular disease

Background Cytokine-mediated immunity plays a crucial role in the pathogenesis of various autoimmune diseases including systemic lupus erythematosus (SLE). The aim of this study was to evaluate association between serum levels of IL-23 and vascular involvement in SLE patients. Materials and methods Study was performed in 94 SLE patients (82 women and 12 men) aged 19–73 years and in 27 age and gender matched controls. Serum IL-23 was measured with ELISA method using R and D Systems tests. Carotid intima-media thickness and the presence of atherosclerotic plaques in carotid and lower extremities arteries were analysed with B-mode ultrasound. Ankle-brachial and high resistance indexes were measured with Doppler ultrasonography. We took into account classical cardiovascular risk factors (hypertension, dyslipidemia, hyperglycemia, overweight/obesity, smoking, oral contraceptives, positive family history of cardiovascular disease), selected clinical manifestations (cardiovascular, cerebrovascular, lupus nephritis, Raynaud’s phenomenon, livedo reticularis, vasculitis, other thromboembolic complications), profile of autoantibodies (antinuclear, antiphospholipid, anti-neutrophil cytoplasmic, anti-endothelial cell). Statistical analysis was performed with: chi 2Yates, chi 2Pearson, rank Spearman correlations tests, logistic regression analysis and multivariate stepwise analysis. Results Concentrations of IL-23 significantly differed between SLE patients and the controls (p=0.0005). Patients with high levels of IL-23 more frequently developed atherosclerosis showed as the presence of plaques in right common femoral artery (OR=10.1; 95% CI:1.2–85.1) and lupus nephritis (OR=3.2; 95% CI:1.1–9.6). Among classical atherosclerotic risk factors only obesity was significantly associated with IL-23 (OR=3.8; 95% CI:1.2–12.3). Immunological characteristics significantly related to IL-23 were anti-phosphatidylethanolamine antibodies (OR=12.7; 95% CI:1.5–108.1) and anti-SS-B antibodies (OR=11.8; 95% CI:1.5–94.8). Association with anti-cardiolipin and anti-prothrombin antibodies was on the border of statistical significance (OR=2.3; 95% CI:0.9–5.7 and OR=8.4; 95% CI:1.0–71.1 respectively). Conclusions IL-23 may be involved in lupus nephritis pathogenesis. 2. IL-23 through its significant association with obesity and antiphospholipid antibodies may promote hypercoagulable state contributing to atherothrombosis development in SLE patients.

A5.07 The role of immunologic and inflammatory factors in the risk of microvascular and macrovascular impairment development in systemic lupus erythematosus – preliminary data

Background and objectives Vascular disorders are a well recognised clinical problem in systemic lupus erythematosus (SLE). This preliminary study was designed to evaluate the association between cerebral circulation changes, carotid arteries involvement as well as nailfold capillaroscopy (NC) abnormalities and immunologic/inflammatory markers, classical atherosclerosis risk factors and organ involvement in SLEpatients. Materials and methods The study was performed in 30 SLE patients. Bilateral transcranial doppler (TCD) monitoring over the middle cerebral arteries according to the criteria of the International Consensus Group on Microembolus Detection was performed using two 2-MHz probes of the pulsed Doppler system MultiDop-T Digital (DWL Compumedics). MRI scans of the brain were carried out using a 1.5-T scanner GE Discovery 450 (GE Healthcare). Detection of carotid stenosis was performed using 3D contrast-enhanced MR angiography. Carotid intima-media thickness (cIMT) was measured with B-mode ultrasound. NC was done using Zeiss device. More than 100 variables were taken into account including cytokines, inflammatory markers, autoantibodies, classical risk factors for atherosclerosis and selected organ manifestations. Statistical analysis was performed with chi2 Yates, chi2 Pearson, rank Spearman correlations tests and logistic regression analysis. Results Factors which significantly correlated with analysed vascular changes including microemboli in TCD, ischaemic changes in MRI and NC abnormalities, were thrombocytopenia (r = 0.47, p = 0.01), C-reactive protein (CRP) (r = 0.51, p = 0.0039) and antiphospholipid antibodies (aPLs) (r = 0.55, p = 0.0015). There was significant association between vascular endothelial growth factor (VEGF) and IL-6 and high cIMT (r = 0.36, p = 0.0492, r = 0.41, p = 0.0239, respectively) as well as NC abnormalities, especially megacapillaries presence (r = 0.38, p = 0.0415, r = 0.42, p = 0.0226, respectively). Additionally, patients with changes in NC significantly more frequently were dyslipidemic (r = 0.56, p = 0.0015), hypertensive (r = 0.41, p = 0.0252) and unveiled high titers of anti-dsDNA (r = 0.37, p = 0.0492) and cardiac involvement (r = 0.38, p = 0.0441). There was also important positive correlation between cIMT and NC abnormalities (r = 0.40, p = 0.0300) as well as microemboli in TCD (r = 0.44, p = 0.0211). Finally, microemboli in TCD were associated with MRI ischaemic changes (r = 0.45, p = 0.0177). Conclusions NC and cIMT provide the optimal protocol to screen SLE patients for cardiovascular risk. CRP, VEGF, IL-6, aPLs and anti-dsDNA seem to be crucial pathogenic factors in micro- and macrovascular impairment development in SLE. Patients with higher cIMT and aPLs should undergo TCD for cerebrovascular risk assessment.

A6.25 Serum concentrations of vascular endothelial growth factor in systemic lupus erythematosus – association with autoantibody profile and cardiovascular involvement

Background and objectives Angiogenesis plays a significant role in the pathogenesis of systemic lupus erythematosus (SLE). Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis as well as vasculogenesis. The study was designed to evaluate the association between VEGF concentrations and immunological parameters, inflammatory markers, classical atherosclerosis risk factors and vascular disorders in SLE patients. Materials and methods The study was performed in 83 patients with SLE and 20 age and gender matched controls. The concentrations of VEGF was determined with ELISA method using R&D Systems tests. The presence of inflammatory markers (ESR, CRP and fibrinogen) and selected autoantibodies - anti-endothelial (AECA), anti-nuclear, anti-phospholipid (aPL) and anti-neutrophil cytoplasmic was evaluated. Classical risk factors for atherosclerosis as well as selected organ manifestations (cardiovascular and central nervous system, lupus nephritis, thromboembolic disorders and vasculitis) were taken into account. Carotid intima-media thickness and atherosclerotic plaques were measured with B-mode ultrasound method. Statistical analysis was performed with chi2Yates, chi2Pearson, rank Spearman correlations tests, logistic regression analysis and multivariate stepwise analysis. Results VEGF levels did not differ significantly between SLE patients and the controls (p > 0.1). The cut-off value of VEGF concentrations was established at 382.4 pg/ml (75- percentile). VEGF levels > 382.4 pg/ml were significantly associated with the elongation of activated partial thromboplastin time (OR = 22.8; 95% CI: 2.3–230.6) and the presence of aPL: anti-prothrombin (aPT) IgA class (OR = 10.7; 95% CI: 2.1–53.4), anti- β2-GPI IgA class (OR = 3.5; 95% CI: 1.1–10.8) and anti-oxidised low density lipoprotein antibodies (OR = 4.8; 95% CI: 1.0–22.8). Myocardial relaxation disorders were significantly more frequent in patients with high concentration of VEGF (OR = 8.0; 95% CI: 1.6–39.5). The low concentration of VEGF significantly decreased the risk of the existence of selected autoantibodies: aPT IgA (OR = 0.18; 95% CI: 0.0–0.72), aβ2-GPI IgA (OR = 0.17; 95% CI: 0.04–0.71), anti-double stranded DNA (OR = 0.31; 95% CI: 0,11–0.91) and AECA (OR = 0.30; 95% CI: 0,11–0.85). Furthermore, they were associated with reduction of the risk of atherosclerotic lesions in iliac arteries (OR = 0.24; 95% CI: 0.0–0.99) and vasculitis development (OR = 0.17; 95% CI = 0.03–0.91). Conclusions 1. High VEGF levels may increase the prothrombotic risk in SLE patients because of the significant association with the presence of antiphospholipid antibodies. 2. The lower concentrations of VEGF significantly decrease the risk of persistence of selected autoantibodies and atherosclerotic lesions as well as vasculitis development in SLE patients.

A3.13 The high resistance index values are decreased in systemic lupus erythematosus patients – risk factors and clinical association

Background High resistance index (HRI), evaluated on the basis of Doppler spectrum of popliteal arteries, enables detection of subclinical changes in small vessels in systemic lupus erythematosus (SLE) patients. Objective To evaluate the association between decreased values of HRI in SLE patients and selected immunological parameters, the presence of markers of inflammation and classical risk factors for atherosclerosis and also selected clinical manifestations. Methods The investigation was performed in 76 patients with SLE (age 20-73 years). The mean course of the disease was 8.7 years. The coexistence of APS was confirmed in 17 patients (22.4%). The control group consisted of 30 healthy people. All the duplex Doppler examinations of popliteal arteries were performed with HDI 3500 (ATL) using 5- 12 MHz linear transducer under standardised conditions. We evaluated the presence of anti-endothelial antibodies (AECA) and profiles of anti-nuclear antibodies, anti-phospholipid antibodies (aPL) and anti-neutrophil cytoplasmic antibodies. We also analysed markers of inflammation (C-reactive protein, erythrocyte sedimentation rate and fibrinogen), classical risk factors for atherosclerosis (hypertension, hyperglycaemia, hyperlipidaemia, smoking and positive family history for cardiovascular disease) and clinical complications including cardiovascular and central nervous system manifestations, lupus nephritis, thromboembolic disorders and vasculitis. Statistical analysis was performed with chi2Yates, chi2Pearson, rank Spearman correlations tests. Logistic regression analysis and multivariate stepwise analysis were also done. All statistical analyses were performed with STATA 11. Results We found that HRI values in patients with SLE were significantly lower in comparison with the control group (p< 0.0001). We also showed that the coexistence of APS significantly increased risk of lower values of HRI presence (OR = 11.40; 95% CI:1.69-77.03), and from among aPL the most significant were aCL IgG (OR = 7.43; 95% CI:1.82-30.36), aCL IgM (OR = 7.83; 95% CI:1.08-56.53) and anti- β2-GPI antibodies (OR = 5.76; 95% CI:1.17-28.26). Other serological markers, which significantly influenced decreased values of HRI were AECA (OR = 14.84; 95% CI:2.76-79.66). Furthermore, we found significant negative correlation between HRI values and the presence of thromboembolic disorders (R = -0.25; p = 0.0299) and the duration of SLE (R = -0.23; p = 0.0427). We have found no associations between decreased HRI values and the rest of analysed variables. Conclusions 1. HRI values are significantly decreased in SLE patients. 2. The coexistence of APS and the presence of aPL and AECA are risk factors for decreased HRI values in SLE patients. 3. There is a significant reverse relationship between HRI values and the duration of the disease and the presence of thromboembolic changes in SLE patients.