Factors of Progression and Occurrence of Atherosclerosis in Rheumatoid Arthritis.

Aim      To determine in a prospective study factors of progressive atherosclerotic lesion of blood vessels in patients with rheumatoid arthritis (RA).Material and methods  This prospective study included 124 patients with RA and suspected ischemic heart disease (IHD) and 30 patients with IHD (comparison group) aged 58 [52; 63] years. On enrollment to the study and at 3 years of follow-up, all patients underwent clinical and instrumental examination according to European and Russian guidelines for diagnosis and treatment of stable IHD (2013), including coronography as indicated. For all RA patients of the comparison group, risk factors (RF) were evaluated, including arterial hypertension, smoking, excessive body weight, family history of cardiovascular diseases (CVD), diabetes mellitus, and dyslipidemia. The following laboratory data were evaluated: blood count; biochemistry, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), rheumatoid factor (RhF), cyclic citrullinated peptide antibodies, and high-sensitivity C-reactive protein (hsCRP). Proinflammatory cytokines, including interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF- α), were measured in RA patients once, at 3 years of follow-up.Results Incidence of FRs for CVD was similar in RA patients and in the comparison group. Median RA duration before inclusion into the study was 11 years, and median DAS28 index score was 3.8. Incidence of dyslipidemia due to increased TC, LDL-C, and HDL-C was higher for RA patients at baseline. The LDL-C goal (<1.8 mmol/l) was achieved only in 3 (10 %) patients of the comparison group and 10 (8 %) RA patients. RA patients had higher levels of the inflammation indexes, hsCRP (0.75 mg/dl vs. 0.16 mg/dl; p<0.05) and erythrocyte sedimentation rate (ESR) (15 mm/h vs. 11.5 mm/h; p<0.05). In the RA group at baseline, atherosclerotic plaques with carotid artery (CTA) stenosis of 20% or more were found in 94 (77 %) patients; in 3 of them, CA stenosis was >50%. Patients with RA frequently had unchanged or slightly changed coronary arteries (CA) (47% of patients), and less frequently they had hemodynamically significant multi-arterial coronary atherosclerotic lesions (7 % vs. 57 % of patients in comparison group). At 37.5 months, 21 (23 %) of 94 RA patients had progressive atherosclerosis in CA and/or CTA; 12 (13 %) RA patients had only progressive CA atherosclerosis; 7 (8 %) had only progressive CTA atherosclerosis; and 2 (2 %) had simultaneous progression of CA and CTA atherosclerosis. Two groups of RA patients were formed, with the progression of atherosclerosis (n=21) and without the progression of atherosclerosis (n=69). RFs for the development/progression of atherosclerosis in RA patients included smoking, family history of CVD, and duration of the disease. Levels of lipids did not differ. Levels of proinflammatory cytokines (IL-1ß, IL-6, TNF-α) were higher in RA patients with progressive atherosclerosis. No effects of the anti-rheumatic therapy on the progression of atherosclerosis were observed.Conclusion      Progression of atherosclerosis in RA remains in disease with low and moderate activity during the anti-rheumatic and hypolipidemic treatment. The development of atherosclerosis in RA is determined by lipid, inflammatory, and immune disorders.

Creation of a recombinant Komagataella phaffii strain, a producer of proteinase K from Tritirachium album.

The objects of the study were recombinant clones of Komagataella phaffii K51 carrying the heterologous proteinase K (PK-w) gene from Tritirachium album integrated into their genome as well as samples of recombinant proteinase K isolated from these clones. The aims of this work were i) to determine whether it is possible to create recombinant K. phaffii K51 clones overexpressing functionally active proteinase K from T. album and ii) to analyze the enzymatic activity of the resulting recombinant enzyme. The following methods were used: computational analysis of primary structure of the proteinase K gene, molecular biological methods (PCR, electrophoresis of DNA in an agarose gel, electrophoresis of proteins in an SDS polyacrylamide gel under denaturing conditions, spectrophotometry, and quantitative assays of protease activity), and genetic engineering techniques (cloning and selection of genes in bacterial cells Escherichia coli TOP10 and in the methylotrophic yeast K. phaffii K51). The gene encoding natural proteinase K (PK-w) was designed and optimized for expression in K. phaffii K51. The proteinase K gene was synthesized and cloned within the plasmid pPICZα-A vector in E. coli TOP10 cells. The proteinase K gene was inserted into pPICZα-A in such a way that - at a subsequent stage of transfection into yeast cells - it was efficiently expressed under the control of the promoter and terminator of the AOX1 gene, and the product of the exogenous gene contained the signal peptide of the Saccharomyces cerevisiae a-factor to ensure the protein's secretion into the culture medium. The resultant recombinant plasmid (pPICZα-A/PK-w) was transfected into K. phaffii K51 cells. A recombinant K. phaffii K51 clone was obtained that carried the synthetic proteinase K gene and ensured its effective expression and secretion into the culture medium. An approximate productivity of the yeast recombinant clones for recombinant proteinase K was 25 µg/ mL after 4 days of cultivation. The resulting recombinant protease has a high specific proteolytic activity: ~5000 U/mg.

[Level of N-terminal fragment of brain natriuretic peptide progenitor and atherosclerotic damage of brachocephalic arteries in patients with rheumatoid arthritis with inefficiency and/or injurability of basic anti - inflammatory treatment].

The high prognostic significance of the concentration of the N-terminal - pro-B-type natriuretic peptide (NT-proBNP) in the development of cardiovascular diseases (CVD) was identified for rheumatoid arthritis (RA) and general populations. AIM: to investigate the significance of NT-proBNP level in patients (pts) with RA with the ineffectiveness and/or intolerance of basic anti - inflammatory therapy; compare the level of NT-proBNP with atherosclerotic lesion of the brachiocephalic arteries (BCA), traditional risk factors and inflammatory markers. MATERIALS AND METHODS: The investigation enrolled 28 pts (24women/4men) with the lack of efficacy/resistance and/or intolerance of basic anti - inflammatory drugs (DMARDs); median age was 55 [46; 61] years, median disease duration 114 [60; 168] month; DAS28 6,2 [5.1; 7.0]; SDAI 35.0[23.9; 51.0], CDAI 30.0[21.0; 42.0], serum positivity for rheumatoid factor (RF) (100%)/anti - cyclic citrullinated peptide antibodies (ACCP) (86%). The study did not include RA pts with congestive heart failure. High incidence of traditional risk factors was found in RA pts: arterial hypertension - in 75%, dyslipidemia - 61%, smoking - 17%, overweight - 61%, family history of cardiovascular diseases - 36%, hypodynamia - 68%. Coronary artery disease was diagnosed in 11% RA pts. Lack of efficacy of 3 or more DMARDs was found in 46% of pts, intolerance to previous therapy with DMARDs - in 54% pts. 47% were receiving methotrexate (20 [18; 25] mg/week), 11% - leflunomide, 7% - sulfasalazine, 46% - glucocorticoids, 75% - non - steroidal anti - inflammatory drugs. The control group consisted of 20 healthy donors, comparable to pts by age and sex. Serum levels of of NT-proBNP were measured using electrochemiluminescence method Elecsys proBNP II (Roche Diagnostics, Switzerland). The determination of the intima - media thickness (IMT) BCA were assessed from duplex scanning. Atherosclerotic lesion of BCA was assessed by the presence of atherosclerotic plaque (IMT ≥1.2 mm). RESULTS: NT-proBNP concentrations in RA pts proved to be higher (78.7 [41.4; 101.3] pg/ml) than those in the control group (55.3 [36.6; 67.3] pg/ml, p100 pg/ml - 1 group (n=6) and ≤100 pg/ml - 2 group (n=22). Groups of RA pts did not differ in gender, age, activity of RA, frequency of detection of traditional risk factors. Atherosclerotic lesion of the BCA was detected in 3 (50%) pts of the 1 group and in 8 (36%) pts of the 2 group (p>0.05). In RA pts the level of NT-proBNP correlated with age (r=0.39; p.

[Cardiovascular disease in rheumatic diseases].

The representatives of immunoinflammatory diseases are rheumatic ones, such as primarily rheumatoid arthritis, juvenile idiopathic arthritis, spondyloarthritis, psoriatic arthritis, systemic lupus erythematosus, and other systemic connective diseases, which are characterized by a high risk for untimely death. The high risk of untimely death in these diseases has been found to be associated with the severity of an immunoinflammatory process that gives rise to severe irreversible damage to vital organs and systems and with the development of a wide spectrum of comorbidities (infections, interstitial lung disease, malignant tumors, osteoporotic fractures, etc.). Among them, diseases of the cardiovascular system, which are most commonly caused by the early development and.accelerated progression of atherosclerotic coronary lesions, hold a central.position. The paper gives the data available in the recent literature on the impact.of antirheumatic therapy (disease-modifying antirheumatic drugs and biological agents) on' the cardiovascular system.

[Interleukin-6 inhibition and cardiovascular disease in patients with rheumatoid arthritis].

Rheumatoid arthritis (RA) is a' disease conferring high risk for cardiovascular events (CVE). Systemic inflammation underlying RA favors development of CVE. The safety of biological agents, acting on the cardiovascular system has been inadequately investigated. On the one hand, they decrease RA activity and, on the other, may increase the risk of CVE. This review analyzes' the literature data predominantly published in recent years on the effect of an IL-6 receptor inhibitor on the cardiovascular system. Tocilizumab is shown to be a promising agent to reduce cardiovascular risk the findings need to be clinically verified. Long-term prospective investigations should be conducted to determine more exactly the impact of IL-6 receptor inhibition on. the development of CVE.

[Cardiovascular risk in patients with psoriatic arthritis].

Psoriatic arthritis (PsA) is a chronic.immune-mediated disease that is observed in 8-30% of psoriatic patients. It has been recently established that PsA and psoriasis are closely associated with the high prevalence of metabolic syndrome, hypertension; abdominal obesity, and a risk for cardiovascular diseases (CVD), including fatal myocardial infarction (Ml) and acute cerebrovascular accidents, which shortens lifespan in the patients compared to the general population. The authors state their belief that the synergic effect of traditional risk factors (RFs) for CYD and systemic inflammation underlie the development of atherosclerosis in PsA. It is pointed out that the risk of CYD may be reduced not only provided that the traditional RFs for CVD are monitored, but also systemic inflammation is validly suppressed. The cardioprotective abilities of methotrexate and tumor necrosis factor-a (TNF-a) inhibitors are considered; the data of investigations showing that the treatment of PsA patients with TNF-a inhibitors results in a reduction in carotid artery intima-media thickness are given. lt is noted that there is a need for the early monitoring of traditional RFs for CVD in patients with PsA and for the elaboration of interdisciplinary national guidelines.

[N-terminal pro-brain natriuretic peptide levels and diastolic dysfunction in patients with early rheumatoid arthritis before the administration of disease-modifying antirheumatic drugs].

AIM: To determine N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in patients with early rheumatoid arthritis (RA) before the use of disease-modifying antirheumatic drugs (DMARDs); to compare NT-proBNP values with traditional risk factors (TRF), cardiovascular diseases (CVD), inflammatory markers, and left ventricular (LV) diastolic dysfunction (DD). SUBJECTS AND METHODS: The investigation enrolled 74 patients with a valid RA diagnosis (the 2010 ACR/EULAR criteria), 56 (74%) women, median (Me) age, 54 years; disease duration, 7 months; seropositive for IgM rheumatoid factor (87%) and/or anti-cyclic citrullinated peptide antibodies (100%) with no history of the use of DMARDs and glucocorticosteroids. Duplex scanning and echographic findings were used to assess TRF for CVD and carotid artery atherosclerosis (CAA) in all the patients with early RA prior to therapy. An E/A ratio was used as a criterion for LVDD. RESULTS: NT-proBNP concentrations in patients with early RA proved to be higher than those in the control group (p<0.0001). Higher-than-normal NT-proBNP levels were seen in 36 (49%) patients. The patients with early RA and elevated NT-proBNP values were older and had a higher body mass index (BMI) than those with normal NT-proBNP levels. Those with elevated NT-proBNP concentrations were more frequently found to have CAA, coronary calcification, and coronary heart disease; their intima-media thickness was also larger and C-reactive protein (CRP) levels higher than in those with normal NT-proBNP values. There were correlations between NT-proBNP levels and erythrocyte sedimentation rate, CRP, simplified disease activity index, and clinical disease activity index. Multivariate analysis revealed that chronic heart failure (CHF), CAA, CRP and low-density lipoprotein (LDL) levels, and BMI correlated with NT-proBNP concentrations. LVDD was detected in 35 (48%) patients with early RA. The level of NT-proBNP in patients with DD was higher than in those without DD. Higher-than-normal NT-proBNP values were observed in 23 (65%) and 12 (32%) patients with and without LVDD, respectively. The optimal NT-proBNP level for CHF detection was equal to 237.4 pg/ml (86% sensitivity and 85% specificity); the area under the ROC curve was 0.879. CONCLUSION: Just at the early disease stage, the patients are noted to have a high NT-proBNP level that is influenced by higher BMI, low LDL levels, CAA, CHF, and high CRP values. In the patients with early RA, the diagnostically significant NT-proBNP concentration for CHF detection was higher (237 pg/ml) than in those without RA (125 pg/ml). The patients with early RA should undergo NT-proBNP determination, LVDD screening, correction of TRF for CVD, atherosclerosis treatment, and remission achievement.

[Cardiovascular Complications of Rheumatoid Arthritis: Prevalence and Pathogenesis].

Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with high risk of cardiovascular events. Among main causes of death in RA are: myocardial infarction, cerebrovascular accident, sudden cardiac death, which are determined by the early development and rapid progression of atherosclerotic vascular lesions. According to studies high risk of cardiovascular events is not explained by only classical risk factors. It is assumed that there are additional mechanisms of development of adverse outcomes such as systemic inflammation, increased arterial stiffness, and endothelial dysfunction. In this literature review we present various risk factors of cardiovascular events in patients with RA and their relation to RA pathogenesis.

[Left and right ventricular diastolic dysfunction in patients with early rheumatoid arthritis before prescribing disease-modifying antirheumatic therapy].

AIM: To estimate the rate of diastolic dysfunction (DD) of the left and right ventricles (LV and RV) in patients with early rheumatoid arthritis (RA) before using disease-modifying antirheumatic drugs (DMARDs) therapy and to investigate its association with traditional risk factors (TRFs) for cardiovascular diseases (CVD) and inflammatory markers. SUBJECTS AND METHODS: The investigation enrolled 74 patients with a valid diagnosis of RA, including 56 (74%) women (median age, 54 years; disease duration, 7 months); the patients who were seropositive for rheumatoid factor (RF) (87%) and/or anti-cyclic citrullinated peptide (anti-CCP) antibodies (100%) who had not been on DMARDs or glucocorticosteroids. TRFs for CVD and carotid artery atherosclerosis were assessed from duplex scanning data and echocardiography was performed in all the patients with early RA before starting the therapy. The ratio of the maximum blood flow velocity during early diastolic filling (E) to that during atrial systole (A) was used as a criterion for LVDD and RVDD. There were 3 types of impaired ventricular filling: 1) E/A <1; 2) E/A = 1-2; 3) E/A > 2. RESULTS: LVDD and RVDD were detected in 35 (48%) and 17 (23%) patients, respectively. RVDD was recorded only in conjunction with LVDD. Among LVDD and RVDD, the former was prevalent. All the patients with early RA were divided into 3 groups: 1) patients with LVDD and RVDD; 2) those with LVDD; 3) those without ventricular DD. All the three groups were matched for the level of DAS28, anti-CCP antibodies, and RF. The incidence of arterial hypertension, dyslipidemia, and abdominal obesity was higher in the patients of Groups 1 and 2 than in those of Group 3. There was a progressive decrease in high-density lipoprotein (HDL) cholesterol concentrations and increases in triglyceride (TG) levels and atherogenic index from Group 3 to Group 1, with the concentrations of total cholesterol and low-density lipoprotein cholesterol being similar in the 3 groups. Coronary heart disease was recorded more frequently in Group 2 than in Group 3. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) proved to be also significantly higher in the patients with DD than in those without DD. Correlations were found between LV E/A and ESR, CRP, HDL cholesterol, TG, RV E/A and ESR, DAS28, TG. CONCLUSION: The patients with early-stage RA were found to have high incidence rates of LVDD and RVDD, which is related to the high prevalence of CVD, the high spread of TRF for CVD, and the high activity of an inflammatory process.

[Clinical and hemodynamic characteristics and possibilities for therapy in patients with severe (functional class IV) pulmonary arterial hypertension associated with diffuse connective tissue diseases].

AIM: To study the clinical and hemodynamic characteristics of a group of patients with Functional Class (FC) IV pulmonary arterial hypertension (PAH) developing in the presence of diffuse connective tissue diseases (DCTD) and to evaluate the efficacy of intravenous iloprost. SUBJECTS AND METHODS: The study enrolled 59 patients with PAN-DCTD, including 7 who had FC IV and 8 who developed this condition during a follow-up. The diagnosis of PAH was based on pulmonary artery catheterization findings. FC IV was diagnosed using the conventional New York Heart Association classification. All the patients received PAH-specific therapy (bosentan, sildenafil); the patients with FC IV had combined therapy; 4 patients were treated with intravenous iloprost calculated with reference to 0.5-2.5 ng/kg/min for 15 days. In addition to the patients with FC IV, 3 patients with unstable FC Ill were given iloprost. Besides targeted therapy, all the patients received standard treatment, including diuretics, and ionotropic therapy. RESULTS: Evaluation of hemodynamics in patients with different FCs revealed the most important differences in right atrial pressure, cardiac output, cardiac index, and pulmonary vascular resistance. A linear relationship was seen between the level of this indicator and FC, the closest correlation being for hemodynamic parameters characterizing right ventricular systolic function. There were no changes in mean pulmonary artery pressure; only the patients with FC IV were found to have its slight elevation (from 52 ± 15 to 55 ± 11 mm Hg). Pulmonary artery wedge pressure remained unchanged regardless of FC. Intravenous iloprost was noted to have an obvious positive effect on both clinical and hemodynamic parameters. Catheterization verified improvement in 6 out of the 7 patients; no hemodynamic changes were found in 1 patient during 15-day therapy. CONCLUSION: The patients with FC IV PAH-DCTD have clinical and hemodynamic features responsible for a fatal prognosis. The results of using intravenous iloprost in patients with decompensated PAH associated with scleroderma systematica convince to use its PAH-specific tablets in cases of verified clinical deterioration when taking its dosage form.

AMP-activated protein kinase: structure, function, and role in pathological processes.

Recently, AMP-activated protein kinase (AMPK) has emerged as a key regulator of energy balance at cellular and whole-body levels. Due to the involvement in multiple signaling pathways, AMPK efficiently controls ATP-consuming/ATP-generating processes to maintain energy homeostasis under stress conditions. Loss of the kinase activity or attenuation of its expression leads to a variety of metabolic disorders and increases cancer risk. In this review, we discuss recent findings on the structure of AMPK, its activation mechanisms, as well as the consequences of its targets in regulation of metabolism. Particular attention is given to low-molecular-weight compounds that activate or inhibit AMPK; the perspective of therapeutic use of such modulators in treatment of several common diseases is discussed.

[Cardiovascular diseases in patients with rheumatoid arthritis during long-term methotrexate therapy].

AIM: To compare the prevalence of risk factors, clinical and subclinical manifestations of cardiovascular diseases (CVD) and their complications in methotrexate (MT)-treated and untreated patients with rheumatoid arthritis. SUBJECTS AND METHODS: The investigation enrolled 193 patients (168 women and 25 men) less than 60 years of age (mean age 49 [44; 53] years) with RA. The patients were divided into 2 groups: 1) 69 patients who received MT in a dose of 15.1 [10.2; 21] mg/week for at least 12 months (mean disease duration 25 [18; 48] months); 2) 124 patients who did not take MT. The patient groups were matched for age, gender, disease duration, RA activity, and the rate of rheumatoid factor (RF) seropositivity and extraarticular manifestations. RESULTS: Dyslipidemia was significantly less frequently identified in MT-treated patients (35/69 or 51%) than in MT-untreated ones (85/124 or 69%; p = 0.01). The serum from the patients treated with MT exhibited higher high-density lipoprotein cholesterol concentrations ((1.8 [0.9; 2.0] mmol/l) than in those untreated with MT (1.2 [1.0; 1.6] mmol/l; p = 0,047). In Group 1, hypertension (49%) and diabetes mellitus (3%) were slightly rare than in Group 2 (62 and 13%, respectively; p > 0.05). Carotid atherosclerotic plaques were found in 19 and 16% and intima-media thickness (IMT) enlargement was seen in 53 and 56% of the patients in Groups 1 and 2, respectively. Silent myocardial ischemia was diagnosed in every 10 patients; heart disease (exertional angina, myocardial infarction) was in every 5 patients in both groups. Aortocoronary bypass surgery was performed in 2 (3%) patients from those who received MT and had experienced MI and in one (1.6%) patient from the MT-untreated group. CONCLUSION: Long-term MT therapy was associated with the lower rate of dyslipidemia, but it failed to affect the incidence of CVD in patients with RA.

[Cognitive impairment and anxiety-depressive disorders in patients with rheumatoid arthritis].

Data on the prevalence and features of cognitive impairment in patients with rheumatoid arthritis (RA) are presented. Cognitive impairment was noted in 66% of patients, it did not reach the threshold of dementia and met the diagnostic criteria for moderate cognitive impairment. Anxiety-depressive spectrum disorders were found in 94% patients. Cognitive impairment was associated with apathic affect and anxiety-depressive spectrum disorders (depressive episodes, dysthymia, and elevated anxiety). The impairment of thinking was correlated with the high to moderate inflammatory activity including non-joint RA symptoms, higher levels of proinflammatory cytokines and low doses of glucocorticoids. Cognitive impairment was not associated with the duration and character of standard treatment of RA and concomitant cardiovascular diseases.

[Ten-year risk of cardiovascular complications in patients with rheumatoid arthritis].

AIM: To compare 10-year risk of cardiovascular complications (CVC) assessed by Adult Treatment Panel III (ATP III) and Reynolds Risk Score (RRS); to specify contribution of C-reactive protein (CRP) to development of CVC in patients with rheumatoid arthritis (RA). MATERIAL AND METHODS: The trial included 116 RA patients (100 females and 16 males) and 85 healthy subjects (63 females and 22 males) under 55 years of age free of clinical symptoms of cardiovascular diseases. RA duration and activity were the same in men and women. The patients and controls were matched by age, incidence of standard risk factors (RF). The 10-year risk of CVC development was estimated by two scales--ATP III and RRS. Total cholesterin, HDLP cholesterin were measured with standard enzyme tests, concentration of CRP was assessed by highly sensitive immune nephelometry. RESULTS: The 10-year risk of CVC was higher in RA patients both by ATP III (1.8 - 1;10%) and RRS (2.6 - 2; 7)% compared to the controls (1 - 1;3)% and (1.2 - 1;4)% (p < 0.05). In male RA patients RRS is higher than in females - 7 (3.5; 12)% and 2 (1;2)%, respectively (p < 0.001). Re-calculation from the scale ATP III to RRS has changed the risk in 17 (17%) females and 7 (44%) males with RA. As a result, the number of RA patients with a low CVC risk decreased, with a moderate risk rose 2 times, with a high risk was the same. RRS dependence on the disease duration, RA activity (DAS28) was not registered. RA patients showed a positive correlation of RRS with thickness of the intima-media complex of the carotid arteries (r = 0.44; p < 0.001). CONCLUSION: Introduction of a new prognostic scale RRS allows isolation of groups of patients with moderate and high CVC risk and timely medication of such patients.

[Current knowledge about pathogenesis and treatment of arterial hypertension in rheumatoid arthritis].

Rheumatoid arthritis (RA) is a chronic autoimmune disease with a proved high risk of cardiovascular diseases (CVD). An increase of this risk is mainly due to accumulation of conventional factors of CVD development (arterial hypertension - AH), dislipidemia, et cet). Causes of high prevalence of AH in RA, the role of chronic inflammation, effects of antirheumatic drugs with potentially hypertensive effects are outlined and recommendations on AH prevention and treatment in RA patients are given.

[Prospects for the assessment of cardiac rhythm variability in patients with rheumatoid arthritis and systemic lupus erythematosus].

Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are chronic autoimmune diseases associated with confirmed high risk of cardiovascular pathology. Most low-risk patients develop cardiovascular complications (CVC) with the involvement of traditional factors of limited diagnostic value which requires introduction of new efficacious methods for CVC prognostication. Reduced cardiac rhythm variability (CRV) along with increased levels of inflammation markers is an independent predictor of unfavourable outcome in patients with coronary heart disease, chronic cardiac insufficiency, diabetes mellitus, arterial hypertension, and metabolic syndrome; it may be a consequence of joint contribution of sympatic activation and inflammation to the development of atherothrombotic complications. This review is focused on the methods of CRV evaluation, possible mechanisms of mutual potentiation of autonomous nervous system disturbances and inflammatory process, factors responsible for cardiac autonomous dysfunction in RA and SLE. Much attention is given to the possibilities of correction of vegetative dysregulation of cardiac activity in patients with autoimmune diseases.

[Prevalence of mental disorders in SLE patients: correlations with the disease activity and comorbid chronic conditions].

AIM: To study effects of the disease activity and comorbid chronic conditions on the incidence of mental disorders in patients with systemic lupus erythematosus (SLE) treated in the State Institute of Rheumatology, RAMS. MATERIAL AND METHODS: A total of 115 patients with documented SLE (age 24-45 years, median 34 years, SLE duration 4-17, median 8 years) participated in the study. SLE activity was evaluated by SLEDAI scale, atherosclerosis--by ultrasonic arterial dopplerography, mental disorders--by psychological and psychic scales according to IDC-10. RESULTS: Mental disorders were detected in 76 of 115 (66%) patients: anxiety and depression (83%), depression episodes (40%), maladaptation (24%), generalized anxiety (10%), dysthymia (9%). Manifest cognitive disorders were seen in 7% of examinees. SLE patients with and without mental disorders did not differ by age, gender, SLE duration and activity, cumulative doses of glucocorticoids and cytotoxic drugs, but differed by diagnosed atherosclerosis (23 and 8%, respectively). All SLE patients with the history of myocardial infarction had mental disorders. SLE patients with antiphospholipid syndrome had mental disorders in 85%, while controls--in 49%. CONCLUSION: Mental disorders are found frequently in SLE patients (66%). 83% of these disorders are anxiodepressive. Incidence of mental disorders in SLE patients do not correlate with age, gender, SLE duration and activity, doses of glucocorticoids and cytotoxic drugs, but correlate with comorbid diseases (atherosclerosis, myocardial infarction, acute cerebral attacks, antiphospholipid syndrome and Sjogren's syndrome.

[Clinical implication of assessment of heart rate variability in patients with psoriatic arthritis].

AIM: To evaluate clinical significance of heart rate variability (HRV) in patients with psoriatic arthritis (PsA). MATERIAL AND METHODS: HRV was investigated by means of time-domain analysis of 24 h ECG ambulatory recording in 113 PsA (70 female) patients < 55-years-old and 65 age-matched healthy subjects. We assessed the presence of standard cardiovascular risk factors, performed carotid and femoral ultrasound with measurement of intima-medial thickness (IMT) in PsA patients. Inflammatory markers (CRP, fibrinogen) were detected in all the patients. RESULTS: Significantly lower values of HRV parameters adjusted by Mean NN (SDNNn%, SDNNIN%) were detected in PsA men and women when compared to the control group. There was a significant negative correlation between HRV and disease duration, PsA activity (DAS4, Ritchi index), swollen and tender joint counts, femoral IMT, CRP in PsA males (p < 0.05). SDNNin% was lower in PsA male smokers than in non-smokers (p = 0.03). There was a significant negative correlation between HRV and age, systolic blood pressure, dyslipidemia, body mass index, carotid IMT, CRP, fibrinogen in PsA women. CONCLUSION: Reduced HRV reflects sympatho-vagal imbalance in PsA patients associated with the disease duration and activity, smoking, femoral IMT, markers of inflammation (CRP) in males; with standard cardiovascular risk factors, fibrinogen, CRP, carotid IMT in women, and may be identified as a risk factor for cardiovascular morbidity and mortality in further studies.

[Prevention of cardiovascular diseases in rheumatoid arthritis].

One of the key causes of lethality in rheumatoid arthritis (RA) are cardiovascular catastrophes (myocardial infarction, stroke, sudden cardiac death) resultant from early development and rapid progression of atherosclerotic vascular lesion. The article presents current approaches to prevention of cardiovascular diseases in RA including assessment of overall cardiovascular risk for design of optimal strategy of correction of modification factors increasing probability of cardiovascular complications, strong control over inflammation and adequate use of drugs which may be harmful (glucocorticosteroids, nonsteroid anti-inflammatory drugs). Much attention is paid to perspectives of ACE inhibitors, angiotensin II receptor blockers, statins, TNFalpha inhibitors in prevention of cardiovascular complication in RA

[Clinical significance of the assessment of cardiac rhythm variability in patients with rheumatoid arthritis].

The study included 128 patients below 55 years of age with confirmed diagnosis of rheumatoid arthritis (RA) and 30 age and sex-matched healthy volunteer comprising the control group. They were examined for clinical manifestations and severity of RA, cardiovascular risk factors (smoking, body mass index (BMI), blood lipid level), and serum inflammation markers. Intima-media thickness (IMT) was measured in common carotid arteries by duplex scanning. 24 hour ECG monitoring was performed using a three-channel Astrokard monitor, Meditex, with HRV analysis. HRV values in RA patients proved significantly lower than in healthy subjects. The patients showed inverse correlation of HRV with RA duration and severity, HAQ index, X-ray stage, articular dysfunction, and maximum dose of corticosteroids. Also, HRV values negatively correlated with traditional risk factors (age, systolic and diastolic AP, smoking, and IMT. HRV was reduced in AR patients with high and low BMI compared with patients with normal weight. HRV negatively correlated with inflammation markers (leukocytes, ESR, C-reactive protein). It is concluded that concomitant measurement of HRV and inflammation markers in RA patients taking into account severity of the disease and traditional risk factors may be useful for prognosis of cardiovascular death among patients with RA.