[Efficacy and safety of intravenous methylprednisolone in the treatment of patients with active ankylosing spondylitis: results of a 12-week, prospective, open-label, pilot (METALL) study].

AIM: To evaluate the efficacy and safety of intravenous methylprednisolone (MP) 500 mg in patients with active ankylosing spondylitis (AS) and the inefficiency, intolerability of or contraindications to treatment with 2 or more non-steroidal anti-inflammatory drugs (NSAIDs). SUBJECTS AND METHODS: The investigation enrolled 20 patients (age, 35.35 ± 8.19 years) with a 10.2 ± 9.2 year history of AS who met the modified New York criteria) and had its activity defined as the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4 scores and an inadequate response to and intolerance of ≥ 2 NSAIDs; there were 13 (65%) men. MP was given in a single intravenous dose of 500 mg. The main efficiency criterion (primary study endpoint) was considered to be the number of patients who had achieved an ASAS20 response at week 2. Additional rating criteria (secondary endpoints) (improved BASDAI/ASDAS; decreased erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels; the number of patients achieving ASAS20/40/5/6 responses and ASAS partial remission, and improved ASDAS) were calculated 2, 4, and 12 weeks after MP administration. Safety was monitored estimating the frequency of adverse events (AEs) and controlling vital functions and laboratory indicators. RESULTS: Nine (45%) patients achieved an ASAS40 response at week 2. ASDAS was 3.48 at baseline and 2.21 at week 2 (p < 0.0001). ASDAS clinical improvement was established in 11 (55%) patients at week 2. There were decreases in BASDAI from 6.6 to 3.7 at week 2, to 3.5 at week 4, and to 3.2 at week 12 (p < 0.001). CRP levels declined from 6.1 to 3.15 mg/l at week 2 (p < 0.05), to 2.85 mg/l at week 4 (p < 0.001), and to 4.6 mg/l at week 12 (p < 0.05). ESR was 6.5 mm/h at baseline, 5.5 mm/h at week 2 (p < 0.05), 6.0 mm/h at week 4, and 7.0 mm/h at week 12 (p > 0.05). A total of 13 AEs were recorded and no serious AEs were noted. CONCLUSION: Pulse therapy with MP 500 mg is safe and effective in the short-term treatment of patients with active AS who have achieved no benefits of NSAIDs.

[Heart rate variability in patients with ankylosing spondilitis (Bekhterev's disease)].

AIM: To study autonomous regulation of cardiac activity in patients with alkylosing spondylitis (AS) according to heart rate variability. MATERIAL AND METHODS: A total of 51 male patients aged 35.4 +/- 7.3 years with verified AS participated in the trial. Patients with manifest cardiovascular pathology, disturbances of cardiac rhythm or conduction were not included. All the patients were screened for basic cardiovascular risk factors. AS activity was studied with a clinical index BASDAI and acute phase indices. HRV was analysed by 5-min at rest ECG fragments. The control group consisted of 23 healthy males at the age 35.7 +/- 11.5 years matched by basic cardiovascular risk factors with AS patients. RESULTS: Basic time and frequency HRV parameters were much lower in AS patients than in healthy controls. A significant negative correlation was found between HRV parameters and acute phase parameters (ESR, C-reactive protein, fibrinogen) evidencing for a significant impact of persistent systemic inflammation on autonomic regulation of cardiac activity consisting in regress of parasympathic and/or enhancement of sympathetic activity and leading to reduction of HRV in AS patients. CONCLUSION: AS patients have abnormal autonomic regulation of cardiac activity manifesting with subnormal HRV. This is closely related with the activity of systemic inflammation. Reduced HRV may be one of the factors of a high cardiovascular risk in AS patients.

[Pulmonary hypertension in patients with ankylosing spondilitis: main factors of development].

AIM: To detect factors associated with onset of pulmonary hypertension (PH) in patients with ankylosing spondilitis (AS). MATERIAL AND METHODS: 102 patients aged 38.1 +/- 8.9 years (18-58 years) with a documented diagnosis of AS were examined with estimation of clinical idices, smoking status, spinal motility, chest excurtion, AS activity, severity of functional impairment. External respiration function was assessed at spirography, systolic pressure in the pulmonary artery (SPPA) was studied with echocardiography. PH was stated at SPPA > or = 36 mm Hg. Endothelial function was assessed by dopplerography of the brachial artery in the test with reactive hyperemia (endothelium-dependent vasodilation -EDVD) and nitroglycerin (non-endothelium-dependent vasodilation - NEDVD). As a marker of endothelial affection we used the level of circulating endothelial cells (CEC). RESULTS: PH patients were characterized by older age, body mass index, longer smoking history, AS duration, more severe functional impairment by BASFI, worse spinal motility. Both subgroups had moderate reduction of respiratory volumes. PH patients had much lower EDVD while CEC was higher. CONCLUSION: Some factors were revealed which are associated with PH onset in AS patients irrespective of ERF disorders. Endothelial dysfunction is a pathogenetic link mediating effects of these factors, first of all hypoxia, smoking and persistent systemic inflammation, on blood pressure in the system of pulmonary circulation in AS patients.

[Endothelial dysfunction in patients with Bechterew's disease (ankylosing spondylitis)].

The aim of the study was to assess signs of endothelial dysfunction and lesion in patients with ankylosing spondylitis (AS) of different degrees of activity. Forty-four male patients aged 20 to 45 (mean age 34.2 +/- 6.6 years) with a valid diagnosis of AS and no manifest cardiovascular pathology were examined. According to the degree of disease activity, the patients were divided into two groups: group one included 19 patients with low or moderate disease activity, and group two consisted of 25 patients with a high degree of disease activity. Conventional cardiovascular risk factors were screened, and total coronary risk (TCR) and the risk of fatal cardiovascular events were determined. The functional condition of endothelium was assessed by Doppler examination of the brachial artery in re-reactive hyperemia tests (endothelium-dependent vasodilation--EDVD), and in nytroglycerine test (endothelium-independent vasodilation--EIVD). The level of circulating endothelial cells (CEC) was measured as a marker of endothelial lesion. No significant differences were observed between the groups in terms of most conventional cardiovascular risk factors, TCR, and the risk of fatal cardiovascular events. EDVD was significantly less in patients with a high AS activity vs. patients with low or moderate activity and controls. EIVD after nytroglycerine intake was significantly stronger in both groups not only by comparison with that in controls, but also by comparison with the degree of EDVD, which can also be judged as a manifestation of endothelial dysfunction. The level of CEC in high-activity patients was significantly higher than that in the low to moderate activity group and controls. Thus, patients suffering from AS display signs of endothelial dysfunction and lesion, which are most prominent in high activity of the disease and manifest by a decrease in EDVD with a simultaneous increase in EIVD and CEC level elevation. This shows that patients with high activity of AS are at a higher risk of developing cardiovascular pathology than those with a low level of disease activity and age- and sex-comparable healthy individuals.

[Routine and new risk factors for cardiovascular diseases in patients with ankylosing spondylitis (Bechterev's disease)].

AIM: Analysis of standard and new risk factors (RF) to develop cardiovascular diseases (CVD) in patients with ankylosing spondylitis (AS). MATERIAL AND METHODS: Examination of 96 patients with a documented diagnosis of AS has detected symptoms of CVD (arterial hypertension--AH, ischemic heart disease -IHD) and conventional CVD RF (smoking, hyper- and dyslipidemia, overweight, hereditary predisposition, diabetes mellitus). The SCORE scale assessed the risk of CVD complications within 10 years of ischemic heart disease. The following RF were also studied: the levels of C-reactive protein, fibrinogen, platelets, von Willebrand factor activity, total fibrinolytic plasma activity, left ventricular hypertrophy (LVH) according to echocardiography, intima-media complex thickness of the common carotid artery by USI. RESULTS: Prevalence of AH in the examinees (34.4%), IHD (4.2%) was within population values. Total risk for IHD calculated with consideration of conventional RF in AS patients (6.3 +/- 5.0%) did not differ much from mean populational (6.8 +/- 4.4%) while in the absence of hypertension it was lower (4.1 +/- 2.5 and 5.4 +/- 3.5%, respectively, p < 0.05). The risk for lethal CVD complications proved not high (1.46 +/- 1.34%). However, AS patients have high risk for thrombosis due to elevated levels of prothrombogenic factors (fibrinogen, von Willebrand factor, platelets) and subnormal fibrinolytic blood activity. AS patients also demonstrate frequent LVH (overall 51% and 42.9% in normotensive AS patients). CONCLUSION: Higher risk of CVD death in AS patients than in general population may be caused by additional RF missed at conventional stratification.

[Russian versions of disease activity and functional condition evaluation scale in patients with Bekhterev's disease].

The aim of the study was Russianization and evaluation of the main psychometric properties (reliability, validity, and sensitivity) of the questionnaires BASDAI, BASFI, and DFI After the translation and preliminary approbation of the questionnaires, 65 patients (64 men and 1 woman) with a valid, in accordance with modified New York criteria, diagnosis of ankylosing spondylitis (AS), were included in the study. The reliability of BASDAI, BASFI, and DFI scales was evaluated using test-retest method; the validity and sensitivity of the scales were evaluated as well. Test-retest analysis did not reveal significant differences between the primary and subsequent values of all the questionnaires. Cronbach a internal consistency coefficient was 0.891 for BASDAI, 0.976 for BASFI, and 0.978for DFI, which testified that the results were highly reproducible and reliable. For BASDAI questionnaire there were no significant cor- relations with laboratory indices of AS activity (ESR, C-reactive protein level etc.), but there were significant correlations with BASF values (r = 0.73, p < 0.001) and DFI (r = 0.67, p < 0.001). The values of BASFl significantly correlated with signs of spine flexibility (tests of Schober, Ott, Thomayer, and Forestier), chest wall excursions, the duration of the disease, and the presence of hip joint involvement. DFI values correlated only with some of the listed indices (Schober and Thomayer tests; chest wall excursions). When the sensitivity was tested, only changes in BASDAI values (improvement by 16.1%, p < 0.05) were statistically significant. For BASFI and DFI changes in the values were not significant, but they were more prominent for BASFI (6.4% vs. 1. 7%, respectively). In conclusion, BASDAI questionnaire is a highly reliable and sensitive tool, but it only takes into account clinical signs of the activity of the disease. BASFI and DFI scales possess equal reliability, but the validity and sensitivity of BASFI scale are higher.