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Background. Gout is associated with increased risk of cardiovascular disease (CVD) morbidity and mortality. Therefore, an association between coronary heart disease (CHD) and gout deserves careful examination. The aim of this study was to determine the prevalence of CHD and factors associated with CHD in patients (pts) with gout. Methods. 286 male patients with gout were included; age – 51.2 [42.8; 59.4] years (ys), disease duration – 6.2 [3.8; 12.1] ys. All patients underwent standard clinical examination, screening traditional risk factors (TRF) of CVD. We estimated the adjusted odds ratio (OR) and 95% confidence interval (95% CI). Results. CHD was found in 111 out of the 286 pts (38.8%), MI had a history in 29.7%. Compared to individuals with CHD, participants without CHD were older (56.7 [52.1; 61.1] vs 46.2 [40.6; 53.4] ys), had longer duration of gout (9.3 [4.7; 15.1] vs 5.6 [3.3; 9.7] ys) (for all p

Anti-inflammatory therapy, such as colchicine (COL), has been suggested to affect the incidence of cardiovascular events in patients with calcium pyrophosphate crystal deposition disease (CPPD).Objective: to study the effect of anti-inflammatory therapy with COL, hydroxychloroquine (HC), and methotrexate (MT) on cardiovascular outcomes in patients with CPPD.Patients and methods. The study included 305 patients with CPPD, the majority (62.30%) were women. The average follow-up period was 3.9±2.7 years. Among factors influencing cardiovascular outcome were considered: gender; age; smoking; alcohol intake >20 conventional doses per week; arterial hypertension; a history of cardiovascular diseases (CVD), in particular ischemic heart disease, acute myocardial infarction, acute cerebrovascular accident, chronic heart failure >III stage according to NYHA, as well as type 2 diabetes mellitus (DM); body mass index >25 kg/m2 and >30 kg/m2; cholesterol level (CHOL) >5.1 mmol/l; glomerular filtration rate (GFR) < 60 ml/min/1.73 m2; serum uric acid level >360 μmol/l; hypercalcemia (serum calcium level >2.62 mmol/L); CRP level >2 mg/l; the presence of hyperparathyroidism (parathyroid hormone level >65 pg/ml); CPPD phenotypes (asymptomatic, osteoarthritis with calcium pyrophosphate crystals, chronic arthritis, acute arthritis); intake of COL, HC, MT, glucocorticoids and non-steroidal anti-inflammatory drugs (NSAIDs).Results and discussion. 264 patients were under dynamic observation. Any of the studied cardiovascular events were registered in 79 (29.9%) patients. During the observation period, 46 (17.4%) patients died, in 76.1% of cases the cause of death was CVD. Death from other causes was diagnosed in 11 (23.9%) patients. Non-fatal cardiovascular events were reported in 44 (16.7%) cases. The risk of cardiovascular events was higher in patients over 65 years of age (odds ratio, OR 5.97; 95% confidence interval, CI 3.33–10.71), with serum cholesterol levels ≥5.1 mmol/L (OR 1,95; 95% CI 1.04–3.65), GFR

Endothelial dysfunction associated with chronic microcrystalline inflammation plays a role in the progression of atherosclerosis in calcium pyrophosphate crystal deposition diseases (CPPD).The aim of the study was to assess the dynamics of the development of atherosclerosis based on changes in the thickness of the intima-media complex (ICIM) of the carotid arteries (CA) in patients with CPPD receiving long-term anti-inflammatory therapy (colchicine, methotrexate, hydroxychloroquine).Materials and methods. 26 patients with CPPD and 26 patients with osteoarthritis aged over 18 years old were included. Exclusion criteria: age >65 years; presence of cardiovascular diseases. The blood lipid spectrum, hs-CRP level, anthropometric parameters were determined for all, and Doppler ultrasound ultrasonography of the carotid arteries (CA) was performed. Patients were followed up for not 0.9 mm were detected in 11 of 22 (50%) patients with CPPD and in OA in 8 of 19 (42%) (p=0.39). In dynamics, patients with CPPD revealed a decrease in the number of patients with ICIM>0.9 mm from 42 to 18%. At the same time, in 8 patients with CPPD, ICIM>0.9 mm was combined with a CRP level >0.2 mg/l. Out of 22 patients with CPPD, 14 (64%) patients showed a decrease in the mean values of ICIM, in 2 (9%) patients - an increase, in 5 patients the mean values of ICIM did not change. After 6 months of therapy, out of 11 patients with CPPD with ICIM >0.9 mm, after 6 months of therapy, in 7 cases there was a decrease in the indicator less than the specified value, in 5 of them a decrease in serum CRP level

To this date there have been no studies of subclinical atherosclerosis in the patients with calcium pyrophosphate crystal deposition disease (CPPD); in osteoarthritis (OA) such works are rare.Objective: to assess the prevalence of subclinical atherosclerosis of carotid arteries (CA) in patients with CPPD and OA.Patients and methods. The case-control study included 26 patients with CPPD and OA. The diagnosis of CPPD was based on the criteria of D.J. McCarty, diagnosis of OA was based on national clinical practice guidelines. We recorded data on smoking, blood pressure level. Assessed blood lipid spectrum, serum levels of glucose, creatinine, uric acid, CRP. Obesity was diagnosed in accordance with the WHO recommendations. All patients underwent CA Doppler ultrasonography (DUS). An increase in intima-media thickness (IMT) >0.9 mm was considered a manifestation of subclinical atherosclerosis. The SCORE index was calculated for all patients.Results and discussion. The median serum CRP level was comparable in CPPD and OA. The CRP level >5 mg/L was detected in 8 patients with CPPD and in 3 patients with OA (p=0.09). Initial signs of atherosclerosis were present in 11 (42%) patients with CPPD and in 8 (31%) patients with OA (p=0.39). In CPPD, an increase in IMT was associated with a CRP level of ≥5 mg/L in 19% of cases, and in OA – in 12.5% (p=0.08). An increase in IMT >1.3 mm was not found in patients of both groups.Conclusion. In patients with CPPD and OA, subclinical atherosclerosis is often present according to the CA ultrasound. Early detection of uncomplicated subclinical atherosclerosis in CPPD and OA is necessary for timely initiation of treatment aimed to prevent the progression of atherosclerosis and the development of cardiovascular diseases.

The effect of an inhibitor of interleukin-6 (IL-6) receptors on the state of the cardiovascular system in patients with rheumatoid arthritis remains poorly understood.Objective: to study the effect of therapy with an inhibitor of IL-6 receptors, tocilizumab (TCZ), on the dynamics of modifiable risk factors, total cardiovascular risk, and structural changes in the carotid arteries in patients with rheumatoid arthritis during a 12-month follow-up period.Material and methods. The study included 40 patients with active rheumatoid arthritis (33 women and 7 men) with ineffectiveness and/or intolerance to basic anti-inflammatory drugs (DMARDs); the median age was 55 (49; 64) years, the duration of the disease – 102 (48; 162) months; DAS28 – 6.2 (5.5; 6.7) points; all patients were seropositive for rheumatoid factor, 80% – for antibodies to cyclic citrullinated peptide. Patients received TCZ 8 mg/kg therapy every 4 weeks: 52% received TCZ monotherapy, 48% received combined TCZ therapy with DMARDs. All patients underwent an assessment of traditional risk factors, the total cardiovascular risk was calculated using the mSCORE, and atherosclerotic vascular damage was assessed by the detection of atherosclerotic plaques.Results. After 12 months of TCZ therapy, a decrease in disease activity was noted: remission was observed in 25 patients (64%) with rheumatoid arthritis, low disease activity – in 12 (31%); DAS28, HAQ, CRP and ESR concentrations decreased significantly. А high frequency of traditional risk factors was found in rheumatoid arthritis patients: dyslipidemia – 67%, arterial hypertension – 65%, overweight – 55%, burdened heredity for cardiovascular diseases (CVD) – 35%, smoking – 15%. Every third patient had a combination of three or more traditional risk factors. After 12 months of TCZ therapy, the frequency of traditional risk factors did not significantly change, there was an increase in BMI by 2%, an increase in the concentration of HDL-C in serum by 27%, a decrease in the atherogenic index by 28% (p

Background. Cardiovascular diseases (CVD) is the leading cause of death for gout. Arterial hypertension is a proven CVD risk factor (CVD-RF).Objective. To assess the factors influencing on development of an arterial hypertension in patients with a gout. Subjects and methods. 286 male patients fulfilling Wallace proposed criteria for gout were included in the study: age 51.2 [42.8; 59.4] years, disease duration - 6.2 [3.8; 12.1] years, number of joints involved during disease course - 7 [4; 12], subcutaneous tophi - in 35% of patients, intraosseous tophi - in 44%, nephrolithiasis - in 69%, abdominal obesity - in 71%. All patients underwent standard clinical examination, C-reactive protein (CRP), total cholesterol, triglycerides, low and high density lipoproteins, serum uric acid, serum creatinine, smoking, family history of arterial hypertension, body mass index (BMI), diabetes mellitus was performed by standard procedure. We estimated the adjusted odds ratio (OR) and 95% confidence interval (95% CI).Results. There were two groups of patients with arterial hypertension diagnosed on clinical data: group 1 (with arterial hypertension) - 244 (85%) patients, group 2 (without arterial hypertension) - 42 (15%) patients. The group 1 patients were older (52.3 [44.5; 61.1] vs 41.9 [38.3; 50.1] years old), had longer duration of gout (6.7 [3.9; 13.7] vs 4.5 [3; 7.9]), a higher number of joints involved during disease course (8 [4; 12] vs 5 [3; 9]). The frequency of family history of arterial hypertension (68.3 vs 48.8%), abdominal obesity (55.3 vs 33.3%), nephrolithiasis (71 vs 54.7%), intraosseous tophi (48 vs 21%) was higher in group 1 as compared with group 2, р

Aim. To study the clinical manifestations and factors associated with the presence of chronic heart failure (CHF) in patients with early rheumatoid arthritis (RA) prior to anti-inflammatory therapy. Material and methods. The study included 74 patients with valid diagnosis of RA (criteria ACR/EULAR, 2010), 56 women (74%), median age – 54 [46;61] years, disease duration – 7 [4;8] months; seropositive for IgM rheumatoid factor (87%) and/or antibodies to cyclic citrullinated peptide (100%) prior to taking disease modifying anti-rheumatic drugs and glucocorticoids. CHF was verified in accordance with actual guidelines. The assessment of traditional risk factors for cardiovascular diseases, echocardiography, tissue Doppler imaging, carotid artery ultrasound, were carried out before the start of therapy in all patients with early RA. The concentration of NT-proBNP was determined by electrochemiluminescence. The normal range for NT-proBNP was less than 125 pg/ml.Results. CHF was diagnosed in 24 (33%) patients: in 23 patients – CHF with preserved ejection fraction, in 1 patient – CHF with reduced ejection fraction. 50% of patients with RA under the age of 60 were diagnosed with CHF. NYHA class I was found in 5 (21%) patients, class II – in 15 (63%), class III – in 1 (4%). Positive predictive value of clinical symptoms did not exceed 38%. All patients with early RA were divided into two groups: 1 – with CHF, 2 – without CHF. Patients with RA+CHF compared with patients without CHF were older, had higher body mass index, frequency of carotid atherosclerosis, of ischemic heart disease (IHD), hypertension, C-reactive protein (CRP) levels and intima media thickness. Independent factors associated with the presence of CHF were identified by linear regression analysis: abdominal obesity, CRP level, systolic blood pressure, dyslipidemia, carotid intima thickness, IHD. The multiple coefficient of determination was R2=57.1 (R-0.76, p

Objective: To evaluate the effect of the “treat to target” anti-rheumatic therapy on the course of chronic heart failure (CHF) in patients with early rheumatoid arthritis (RA). Materials and methods: The study included 22 patients (17, or 77% female) with CHF with valid diagnosis of RA (ACR/EULAR criteria, 2010), median (Me) age of 60 years, and median disease duration of 7 months. Ten patients (45%) were seropositive for IgM rheumatoid factor and 22 (100%) had antibodies to cyclic citrulline peptide. Their median (1st; 3rd quartiles) DAS28 was 5.6 [4.8; 6.5]. The diagnosis of CHF was confirmed in accordance with the guidelines on the diagnosis and treatment of CHF by the Russian Society of Specialists in Heart Failure (2013). NT-proBNP levels were measured by electrochemiluminescence (Elecsys proBNP II, Roche Diagnostics, Switzerland). All patients were started on subcutaneous methotrexate (MT) with rapid dose titration to 30 mg weekly. If the MT was insufficiently effective, a biological disease-modifying antirheumatic drug (bDMARD) was added to the therapy after 3 months, mainly a TNF-alpha inhibitor. After 18 months, 10 (45%) patients were in remission and had low disease activity, 6 (60%) patients underwent MT therapy in combination with bDMARDs. Results: At baseline, 21 (95%) patients were diagnosed with CHF with preserved ejection fraction and one patient had CHF with reduced ejection fraction. After 18 months there was an improvement of clinical symptoms, echocardiographic parameters (reduction of the left atrium diameter and the left atrium end-systolic volume index, IVRT, E'LV), and diastolic function of the left ventricle (LV). No episodes of acute CHF deterioration were registered. LV diastolic function normalized in 7 (32%) patients who reached the target level of blood pressure, remission (n=5) and low disease activity (n=2), mainly under the treatment with MT and bDMARDs. In patients with RA and CHF, the NT-proBNP levels decreased from 192.2 [151.4; 266.4] to 114.0 [90.4; 163.4] pg/ml (p

Patients with psoriatic arthritis (PsA) have a higher risk of cardiovascular disease (CVD) compared with the general population. Inflammation and traditional CVD risk factors (RFs), including dyslipidemia, make a significant contribution to the development of CVD and their complications in patients with PsA.Objective: to assess the time course of changes in lipid profile measures in patients with early PsA (ePsA) during adalimumab (ADA) treatment for 3-months.Subjects and methods. The investigation enrolled 16 patients (11 women, 5 men; median (Me) age, 45.5 years) with early PsA (ePsA) (disease duration, 7.7 months). ADA was administered subcutaneously at doses of 40 mg once every 2 weeks for 3 months. Before and 3 months after the start of ADA therapy, DAS, C-reactive protein levels, and traditional CVD RFs, including lipid profile measures (total cholesterol, TC, low-density lipoprotein cholesterol, LDL-C, triglycerides, TG, high-density lipoprotein cholesterol, HDL-C, and atherogenic coefficient, AC) were estimated. Ten-year risk for fatal CVD was assessed using the SCORE scale.Results and discussion. Lipid profile disorders mainly associated with elevated LDL-C levels were revealed in 11 (69%) patients; according to the SCORE scale, the total 10-year risk for fatal CVD was low and moderate in 10 (62.5%) and 6 (37.5%) patients, respectively. A correlation was found between the baseline DAS and TG (r=0.53; p0.05). Conclusion. Lipid profile changes were found in 69% of patients with ePSA and correlated with disease activity. The lower inflammatory activity during ADA therapy was accompanied by elevated TC and TG levels.

Background. Patients with psoriatic arthritis (PsA) have increased risk of cardiovascular diseases (CVD). Anti-tumor necrosis factor (TNF) therapy is an effective in PsA but its cardiovascular effects are poorly understood.Aim. To study the changes in carotid intima-media thickness (c-IMT), parameters of arterial stiffness (AS), ambulatory blood pressure monitoring (AMBP) in early PsA (EPsA) patients during the anti-TNF therapy with adalimumab (ADA).Material and methods. Patients with EPsA (n=16; 11 females, 5 males; median age 45.5 years, EPsA duration – 7.7 months) were included into the study. All patients were treated with ADA 40 mg every other week up to 3 months. At baseline and after 3 months of therapy all patients were assessed for conventional cardiovascular risk factors, DAS (Disease Activity Score) and HAQ (Health Assessment Questionnaire) indices, C-reactive protein (CRP), c-IMT, ABPM. At baseline the 4 patients had arterial hypertension, and all patients received effective antihypertensive therapy. All patients were assessed for AS parameters: carotid-femoral pulse wave velocity (PWVcf) and index of wave reflection (rigidity index; RI, %). c-IMT was measured using a high-resolution B-mode ultrasound machine. The results are presented in the form of a median – Me (25; 75 percentiles).Results. By the end of the 3rd month of therapy, a decrease in the activity of early PsA was observed as compared to baseline values: DAS decreased from 4.6 (2.9; 1.9) to 1.6 (1.3; 1.9), p=0,001; HAQ from 0.93 (0.81; 1.31) to 0.25 (0; 0.56), p=0,001; CRP from 27.2 (9.7; 33.7) to 1.8 (0.8; 3.1) mg/l, p=0.001. EPsA remission (DAS

Rheumatoid arthritis (RA) is a disease with a high cardiovascular risk. The results of works on the impact of antirheumatic therapy on carotid artery (CA) intima-media thickness (IMT) are contradictory. Objective: to assess the time course of changes in CA IMT and CA atherosclerosis (CAA) in patients with early RA during treatment to target at a 18-month follow-up. Subjects and methods. The investigation enrolled patients with early RA (disease duration of less than 12 months), who had not previously taken disease-modifying antirheumatic drugs and glucocorticoids. Duplex scanning (DS) of the CA was performed with IMT measurement at baseline and at 18 months after treatment. Vascular atherosclerotic lesion was recorded when atherosclerotic plaque (ASP) was detected. Starting methotrexate (MTX) monotherapy was prescribed to all the patients, when it showed an insufficient effect at 3 months, a biological agent (BA), such as a tumor necrosis factor-α inhibitor or abatacept, was added. RA remission was noted in 31 (42%) patients at 18 months of treatment. Results and discussion. The investigation included 74 patients with early RA; whose median (Me) age was 56 years, all the patients had moderate or high disease activity (Me DAS28-ESR, 5.4). At baseline, there was increased CA IMT in 51.4% of cases and CAA in 55.4%. At 18 months of treatment, there were no significant IMT changes. New CA ASPs were recorded in 8 (24.2%) patients who had no CAA at the time of inclusion in the investigation (p < 0.05). Nineteen (46.3%) patients were recorded to have the progression that had been identified when including CAA as a considerable increase in the number of ASPs (p < 0.05). The risk of CAA progression was correlated inversely with the mean 18-month level of high-density lipoprotein cholesterol (HDL-Cmean) and directly with the mean concentration of C-reactive protein (CRPmean). There was no significant correlation between HDL-Cmean and CRPmean. The changes of CAA were unassociated with the value of DAS28-ESR, the achievement of RA remission, and antirheumatic therapy (MTX monotherapy, MTX + BA). Conclusion. CAA shows progress in patients with early RA despite they are treated to target. DAS28-ESR remission in RA and ongoing RA treatment option had no substantial impact on the course of CAA. HDL-Cmean and CRPmean are independent risk factors for progression of CAA.

Objective: to investigate the impact of antirheumatic therapy carried out according to the treat-to-target (T2T) principle on the time course of changes in NT-proBNP levels in patients with early rheumatoid arthritis (RA) over an 18- month follow-up period.Subjects and methods. The investigation enrolled 74 patients, comprising 56 (74%) women (median age, 54 years) with a reliable diagnosis of RA (ACR/AULAR criteria (2010)) (disease duration, 7 months); who were seropositive for IgM rheumatoid factor (87%) and/or anti-cyclic citrullinated peptide antibodies (100%) and had not previously taken disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids. All the patients started therapy with subcutaneous methotrexate (MTX), with escalation of the dose to 25-30 mg/week; in the absence of any effect after 3 months, biological agents (BAs) were added in 47 (71%) patients. Following 18 months, 44% of patients achieved RA remission; 51 patients (77%) received cardioprotective therapy. NT-proBNP levels were measured in 66 patients with early RA before and 18 months after treatment. The NT-proBNP value

Cardiovascular events (CVEs) are one of the most common causes of death in patients with psoriatic arthritis (PsA). The increased risk of CVEs in PsA is due to a combination of traditional cardiovascular risk factors (TCVRFs) and common inflammatory mechanisms underlying PsA and atherosclerosis.Objective: to estimate the prevalence of TCVRFs, subclinical atherosclerosis, and coronary artery calcification in young patients with early peripheral PsA.Subjects and methods. The investigation enrolled 25 patients (13 men, 12 women) with early PsA, who had participated in the REMARCA study. Their median age was 36 [27; 46] years; the duration of PsA and psoriasis was 5 [3; 7] and 13 [9; 84] months, respectively; DAS was 3.8 [3.4; 5.4].All the patients underwent assessment of TCVRFs, Doppler ultrasound (DUS) of the carotid arteries (CA), evaluation of CA calcification (CAC) using multislice computed tomography (MSCT) and echocardiography, as well as 24-hour blood pressure monitoring.Results and discussion. The patients with early PsA were found to have the following TCVRFs: hypertension in 11 (44%), abdominal obesity in 14 (56%), smoking in 16 (64%), a family history of cardiovascular disease in 6 (24%), menopause in 5 (20%), and dyslipidemia in 14 (56%). There was one TCVRF in 7 (28%), two TCVRFs in 6 (24%), three TCVRFs in 2 (8%), four TCVRFs in 4 (16%), and five TCVRFs in 6 (24%). A combination of three or more TCVRFs was found in 12 (48%) patients.Calculation of ten-year total coronary risk scores identified low [17 (68%)], moderate [6 (24%)], high [1 (4%)], and very high [1 (4%)] risk groups among the patients with a history of acute cerebrovascular accident. Analysis of the relationship between PsA activity and total coronary risk scores revealed no significant differences. Thus, the patients with moderate PsA activity showed low, moderate, and high coronary risks in 7 (70%), 2 (20%), and 1 (10%) cases, respectively.Those with high PsA activity had low, moderate, high, and very high risks in 10 (66.7%), 4 (26.6%), and 1 (6.7%) cases, respectively. CA DUS revealed atherosclerotic plaques (ASPs) in 8 (32%) patients and increased CA intima-media thickness (IMT) values of >0.9 mm in 8 (32%). MSCT showed signs of CAC in 4 (16%) patients. There was a correlation of IMT values with low-density lipoprotein (r = 0.48; p = 0.03), total cholesterol (r = 0.53; p = 0.01), systolic blood pressure levels (r = 0.59; p = 0.02), and abdominal obesity (r = 0.64; p = 0.001) and an inverse correlation between high-density lipoproteins and C-reactive protein levels (r = -0.52; p = 0.03).Young patients with PsA with early-stage disease have a high prevalence of TCVRFs, CA atherosclerotic changes, and CAC signs with relatively low total coronary risk scores, which may indirectly suggest that chronic inflammation is involved in the development of atherosclerosis.

Metabolic syndrome (MS) is a cluster of metabolic disorders giving rise to atherosclerotic cardiovascular diseases (CVD). The combination of inflammatory activity and a high spread of traditional risk factors (RF) for CVD in patients with psoriatic arthritis (PsA) permits them to be referred to as a higher cardiovascular risk group as compared to the general population.Objective: to estimate the spread of MS and its association with inflammation and subclinical atherosclerosis in patients with PsA.Subjects and methods. This investigation enrolled 128 patients with PsA (61.7% women and 38.3% men); their median age was 43 [34; 49.5] years; the duration of PsA and psoriasis – 7 [3; 13] and 15 [6; 26] years, respectively). There was a preponderance of patients with moderate (3.7 ≥ DAS > 2.4) and high (DAS > 3.7) disease activity: 33 (25.8%) and 74 (57.8%), respectively. MS was diagnosed on the basis of the 2011 National Guidelines of the Russian Cardiology Society for Cardiovascular Prevention. All the patients underwent carotid Doppler ultrasound (CDU) for the diagnosis of subclinical atherosclerosis. Results and discussion. MS was diagnosed in 49 (38.3%) patients with PsA. The most common MS criteria were abdominal obesity in 72 (56.3%) and dyslipidemia [an elevation of low-density lipoproteins (LDL) level in 101 (78.9%), and a decrease in high-density lipoproteins (HDL) level in 65 (50.8)]. Hypertension was diagnosed in 32 (25%). 65 (50.8%) patients were found to have subclinical atherosclerosis, as evidenced by CDU.The patients with MS were older than those without this condition (46 [43; 52] and 39 [31; 46] years, respectively; p < 0.0001). These groups did not differ in PsA duration (15 [7; 29] and 15 [5.5; 25] years respectively; p = 0.47). The patients with MS had higher DAS values (4.4 [3.2; 5.6] and 3.6 [2.5; 4.7], respectively; p = 0.02); mean intima media thickness (IMT) (0.78 [0.72; 0.86] and 0.73 [0.66; 0.77] mm; p < 0.0001) and maximal IMT (0.94 [0.84; 1.03] and 0.84 [0.75; 0.94] mm; p < 0.01). They were found to have significantly more often signs of subclinical carotid atherosclerosis than those without MS (33 (67.3%) and 32 (40.5%) patients, respectively; p = 0.003).There was a statistically significant relationship between IMT and RF for CVD (MS components, such as waist circumference (R = 0.41; p

The mechanisms for lowering a cardiovascular risk (CVR) in patients with early rheumatoid arthritis (RA) when implementing the treat-to-target strategy remain inadequately investigated.Objective: to estimate the time course of changes in blood lipid parameters in patients with early RA during Treat-totarget antirheumatic therapy at an 18-month follow-up.Subjects and methods. Seventy-four patients (73% women; median age, 56 years) with early RA meeting the respective 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria and moderate or high activity (median DAS28-ESR score of 5.4) were examined within the framework of the REMARCA trial. After 6-month treatment, RA activity significantly reduced (p < 0.05). At months 6 to 18, no significant change in RA activity was recorded. After 18 months, remission was observed in 31 (42%) patients: in 17 (55%) on methotrexate (MTX) monotherapy and in 14 (45%) on combined therapy with MTX and a biological agent. Blood lipid levels were determined at inclusion in the investigation, 6 and 18 months later. The values of lipid parameters were estimated in terms of the total CVR. 67.6% of the patients were classified as at very high CVR. At 18 months of treatment, 34 (46%) patients were treated with statins (median atorvastatin and rosuvastatin doses were 10 mg/day each).Results and discussion. Only 12% of the patients had optimal baseline values of just all lipid parameters. The concentration of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) correlated negatively with C-reactive protein (CRP) levels, DAS28-ESR, DAS28-CRP, and HAQ (p < 0.05). After 6-month treatment, there were increases in TC by 7%, LDL-C by 12.5%, and HDL-C by 19.7%, and a decrease in the atherogenic index by 16% (p < 0.05). ΔCRP negatively correlated with ΔTC, ΔLDL-C, and ΔHDL-C (r = -0.3; p < 0.05). A correlation of TC and LDL-C with inflammation markers broke off in the presence of lower RA activity; the investigators began recording a relationship of these lipid parameters to traditional CVR factors. Between 6th and 18th month of treatment, there was no significant change in lipid parameters. Statin therapy resulted in no considerable change in lipid concentrations.Conclusion. The level of lipids negatively correlates with disease activity in the patients with early RA. During antirheumatic treatment, the lipid concentrations are more elevated with a more intensive decrease in CRP levels. With lowered RA activity, the level of lipids correlates with traditional CVR factors more strongly than with inflammation markers.

It is suggested that interleukin (IL)-1β inhibition may promote a reduction in the risk of cardiovascular diseases; however, the mechanism of this impact has not been adequately investigated.Objective: to evaluate the impact of canakinumab therapy on the structural and functional properties of the vascular bed and the stiffness of the vessel wall.Patients and methods. An open-labeled prospective study was conducted in 20 patients with chronic tophaceous gout at the V.A. Nasonova Research Institute of Rheumatology. Among the patients, there were 17 (85%) men and 3 (15%) women. All the patents received a single subcutaneous injection of canakinumab 150 mg. Estimation of high-sensitivity C-reactive protein (hs-CRP) and IL-6 levels, 24-hour blood pressure (BP) monitoring, duplex scanning of the carotid arteries (intimamedia thickness (IMT)), and determination of central artery stiffness (aortic pulse wave velocity (APWV), m/sec) were done before and 14 and 120 days after drug administration; the level of hs-CRP was quantitatively measured using a high-sensitivity immunoturbidimetric assay and the concentration of IL-6 was determined by xMAP technology (Human Grp I Cytokine 27-plex panel on a BioPlex-200 analyzer (Bio-Rad, USA). Antihypertensive lipidlowering therapy was not changed during the investigation. Statistical analysis was carried out using a package of applied Statistica 10.0 programs (StatSoft/Inc., USA).Results. Examination of the common carotid artery indicated that the median IMT that was 0.83 [0.71; 0.94] mm at baseline decreased to 0.74 [0.69; 0.84] mm by the end of the investigation (p = 0.022). The median APWV that was 14.12 [10; 17] m/sec at baseline dropped to 13.1 [11; 14] by the end of the investigation, but statistically insignificantly (p = 0.79). By the end of the investigation, there was a reduction in APWV as related to the baseline level in 13 (65%) patients: 7 of them had not one swollen joint and only 5 patients had a CRP level of > 5 mg/l, which was significantly less frequently than that in patients without positive changes in this index: in 6 (86%) of the 7 patients (p = 0.043). There was a direct correlation of changes in APW with those in serum CRP levels (p = 0.012 and p = 0.047, respectively) after 14 and 120 days and with those in serum IL-6 concentrations following 14 days (p = 0.003). 24-hour BP monitoring showed no significant BP change in the patients after 14 and 120 days after injection. The mean level of total cholesterol and triglycerides remained unchanged.Conclusion. The IL-6 inhibitor canakinumab can have a positive effect on IMT and arterial stiffness. The effect of the drug on the structural and functional properties of the vascular bed is due to the magnitude of its anti-inflammatory activity

Background. According to the some studies tocilizumab therapy (TCZ) in patients with rheumatoid arthritis (RA) is accompanied by deterioration of blood lipid profile. Aim. To study changes in serum lipid parameters in patients with RA treated with a combination of tocilizumab and methotrexate compared with methotrexate alone for 24 weeks of observation. Material and methods. Patients (n=72) with RA were included into the pilot non-randomized 24-week study and divided in two groups: 1) TCZ+MTX group (n=39; women 30; median age 51 [43-55] years; 6 i.v. infusions of TCZ 8 mg/kg + МТX 10-20 mg/week); 2) MTX group (n=33; women 23; mеdian age 56 [48-63] years; MTX 7.5-20 mg/week). Results. At the baseline, similar proatherogenic blood profile was observed in both groups. The patients of MTX group more frequently took statins (n=19; 57.6%) compared with the group TCZ+MTX (n=7; 18%), (p Conclusions. TCZ+MTX combined therapy as well as MTX monotherapy are associated with similar improvement in lipid parameters. Adjusted statin doses may be needed to achieve target serum lipid profile in RA patients.

Aim. To study the effect of «treat-to-target» antirheumatic therapy on diastolic dysfunction of the left (DDLV) and right (DDLV) ventricles in patients with early rheumatoid arthritis (RA) during 18 months of observation.Material and methods. The study included patients with early RA (n=66; 71% women; age - 56 [46; 61] years) with moderate/high activity (DAS28 5.3 [5.0; 6.2]), seropositive on rheumatoid factor (77%) and/or cyclic citrullinated peptide antibodies (100%), disease modifying anti-rheumatic drugs (DMARD) and glucocorticoids naive. Treatment with methotrexate (MTX) with the escalation of the dose up to 25-30 mg/week subcutaneously was initiated in all the patients. After 3 months in 47 (71%) patients biologics were added to MTX due to its inefficiency. In 18 months remission of RA was achieved in 44% of the patients. 51 (77%) patients had a cardioprotective therapy. The target blood pressure (BP) level was achieved in 38 (58%) patients. Evaluation of traditional cardiovascular risk factors, 24-hour BP monitoring and echocardiography were performed in all patients initially and in 18 months of MTX/MTX + biologics use.Results. After 18 months DDLV incidence decreased by 7% (from 49% to 42%; p>0.05) and DDRV incidence decreased by 5% (from 24% to 17%; p>0.05). A more significant decrease in DDLV incidence [from 23 (62%) to 18 (49%)] and of DDRV incidence (from 12 (32%) to 6 (16%)] (р=0.05), was found in MTX + biologics group than in MTX only group [DDLV incidence remained unchanged - 7 (28%), and DDRV incidence increased from 3(12%) to 4 (16%); p>0.05]. The normalization of left ventricle (LV) diastolic function in early RA patients depended primarily on the efficacy of antihypertensive treatment, and of right ventricle (RV) diastolic function - on the achievement of target BP level and RA remission. Reduced erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) plasma levels were associated with the improved LV diastolic function [E/A LV and ΔESR (r=-0,3; pConclusion. In early RA patients after 18 months the downward trend of DDLV incidence and a significant reduction of DDRV incidence were found, more expressed in patients treated with MTX + biologics. The achievement of RA remission and target BP level is a prerequisite for the normalization of LV and RV diastolic function and slowing the progression of heart failure.

Most patients with early rheumatoid arthritis (RA) have a high or very high cardiovascular risk (CVR) before therapy with disease-modifying antirheumatic drugs (DMARDs). Objective: to evaluate the impact of antirheumatic therapy performed in accordance with the Treat-to-Target strategy on the progression of atherosclerosis and CVR in patients with early RA. Subjects and methods. This investigation enrolled 74 patients (72% women; median age, 56 years) with early RA having moderate to high activity (median DAS28, 5.6) who had not previously received DMARDs and glucocorticoids (GCs). All patients were anticyclic citrullinated peptide antibody-positive and 87% of the patients were rheumatoid factor-positive. All patients received methotrexate (MT) subcutaneously with dose escalation up to 25–30 mg/week, in case of its inefficiency at 3 months a biological agent (BA) was added. After 6 months, 39% of the patients achieved remission; 19% had low; 35 and 7% had moderate and high disease activity, respectively. The majority (n = 20 (69%)) who achieved remission received MT monotherapy; 9 (31%) – MT + BA whereas among the patients who did not achieve remission 15 (33%) and 30 (67%) respectively. At baseline and after 6 months of treatment, traditional CVR factors were assessed in all patients, by determining the total coronary risk by the SCORE scale, including that modified by EULAR (mSCORE), carotid artery atherosclerosis (CAA) by duplex scanning data, coronary calcification (CC) by multislice spiral computed tomography and by estimating the degree of CVR.Results and discussion. The rates of hypertension, overweight, abdominal obesity, low activity, smoking, and type 2 diabetes mellitus did not change significantly after 6 months. There were increases in the levels of total cholesterol by 7% (p < 0.05), low-density lipoprotein cholesterol by 9% (p

Objective: to estimate the level of cardiovascular risk in patients with early rheumatoid arthritis (RA) before therapy with disease-modifying antirheumatic drugs (DMARDs).Subjects and methods: Seventy-three patients with early RA who had not previously taken DMARDs or glucocorticoids were examined. Disease activity was assessed by the DAS28, SDAI, and CDAI. All the patients were examined by a cardiologist. The investigators assessed traditional risk factors (RF), by determining the overall coronary risk according tothe modified SCORE scale, the degree of a risk for cardiovascular events (CVE), carried out 24-hour ECG and blood pressure monitoring, echocardiography (EchoCG), and carotid duplex scanning, identified coronary artery calcification by multislice spiral computed tomography, and, if indicated, performed stress EchoCG and coronary angiography.Results. The diagnosis of coronary heart disease was established in 13 patients. NYHA functional class I or II chronic heart failure (HF) was diagnosed in 8 patients, systolic HF in 2, HF with preserved left ventricular ejection fraction in 6 cases. There was left ventricular hypertrophy in 22 (30.1%) patients, carotid atherosclerotic plaques in 26 (35.6%), coronary artery calcification in 30 (41.1%), hypertension in 38 (52.1%), abdominal obesity in 34 (46.6%), dyslipidemia in 40 (54.8%), hypercholesterolemia in 37 (50.7%), hypoalphalipoproteinemia in 21 (28.8%), hypertriglyceridemia in 12 (16.4%), low physical activity in 30 (41.1%), and smoking in 13 (17.8%). Thirty-three of 53 women weremenopausal. Fasting hyperglycemia was found in 11 (15.1%) patients; type 2 diabetes mellitus in 4 (5.5%). Thirty-one (42.5%) patients had at least three RFs. In accordance with the current classification of the degree of cardiovascular risk, very high, high, moderate, and low risks for CVE were observed in 58, 8, 8, and 26% of the RA patients, respectively.Conclusion. Most rheumatoid factor- and anticyclic citrullinated peptide-positive patients with early RA and high disease activity have high and very high cardiovascular risks.

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

Aim. To determine risk factors for severe cardiovascular (CV) events (CVEs) in male patients with crystal-verified gout. Subjects and methods. 251 male patients with crystal-verified gout were prospectively followed up in 2003 to 2013. The mean follow-up period was 6.9±2.0 years. New severe CVE cases and deaths were recorded. Logistic regression was used to analyze the impact of traditional and other risk factors and allopurinol use on the risk for severe CVEs. Results. 32 patients died during the follow-up period. Severe CVEs were recorded in 58 (23.1%) patients; CVE deaths were notified in 22 (8.8%) patients. The risk of all severe CVEs was high for hypertension, increased serum high-sensitivity C-reactive protein (hs-CRP) level (>5 mg/l), ≥ stage III chronic kidney disease (CKD) (glomerular filtration rate, 20 g/day), coronary heart disease (CHD), and a family history of premature CHD. The risk of fatal CVEs was highest for elevated serum hs-CRP level, ≥stage III CKD, a family history of premature CHD, hypercholesterolemia, upper quartile of serum uric acid levels (>552 µmol/l), and regular intake of allopurinol. Conclusion. In addition to the traditional risk factors of CV catastrophes, the presence of chronic inflammation and the impact of high serum uric acid levels may explain the high frequency of CV catastrophes.

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

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 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.

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 III 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.