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.

[Atrial fibrillation and prolonged nocturnal cardiac arrests in a patient with obstructive sleep apnea syndrome. Successful correction of disorders by CPAP therapy]. / Fibrillyatsiya predserdii i dlitel'nye nochnye «ostanovki¼ serdtsa u bol'nogo s sindromom obstruktivnogo apnoe vo sne. Uspeshnaya korrektsiya narushenii pri primenenii SIPAP-terapii.

The case history of a 46-year-old patient with obstructive sleep apnea syndrome was analyzed. The examination revealed fourth-degree obesity, prior myocardial infarction, persistent atrial fibrillation with nocturnal asystoles lasting as long as 14.3 sec. During selected drug therapy and regular application of secondary ventilation (continuous positive airway pressure (CPAP) therapy) used to correct breathing problems, there was a reduction in the signs of circulatory deficiency, cessation of cardiac pauses, and recovery of sinus rhythm. The therapeutic effect persisted during a 24-month follow-up.

[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.

[Single-photon emission computed tomography in the diagnosis of myocardial perfusion abnormalities in patients with rheumatoid arthritis: preliminary data].

Increased cardiovascular morbidity and mortality in patients with rheumatoid arthritis (RA) may be attributed to the fact that a systemic inflammation existing in this disease may trigger the development of atherosclerosis. 99mTC-MIBI (4,2-methoxyisobutyl isonitrile) is a compound that permits myocardial perfusion to be visualized and has been proposed for the evaluation of the latter in patients with RA. Analysis of the results of the studies revealed transient myocardial ischemia areas in patients who did not take methotrexate while those who used it were found to have diminished perfusion areas that were, however, clinical insignificant.

[Influence of valsartan, fluvastatin extended release and their combination on arterial pressure, parameters of lipid metabolism, and endothelial function in patients with hypertensive disease].

BACKGROUND: Search of new optimal treatment strategies, allowing to decrease the risk of atherosclerosis development and cardiovascular events is determined by high prevalence of hyperlipidemia in hypertensive patients. AIM: To study the vasoprotective effects and security of Valsartan (V) or Fluvastatin extended release (XL) (F) and their combination in stage 1 and 2 essential hypertension (EH) with moderate hyperlipidemia. METHODS: 32 patients with EH after 14 days of wash-out period were randomized to receive either V (160 mg o.d.) or F (80 mg o.d.). After 8 weeks of monotherapy combination of V+F was administered to each patient for the next 8 weeks. At baseline, after 8 weeks of monotherapy, and at the end of the study sitting BP, lipids, NOs level and endothelial function were assessed. Endothelial function was measured as flow-mediated vasodilation (FMD) by high resolution ultrasound. Valsartan (Diovan) and Fluvastatin (Lescol XL) were provided by Novartis Pharma AG (Basel, Switzerland). RESULTS: Combination of F (80 mg o.d) with initial therapy by V (160 mg o.d.) led to more significant decrement of BP and significant improvement of FMD.

Angiotensin II receptor blocker telmisartan: effect on blood pressure profile and left ventricular hypertrophy in patients with arterial hypertension.

In this open-label, non-comparative study, the anti-hypertensive efficacy and effect on left ventricular hypertrophy (LVH) of 24 weeks' treatment with once-daily telmisartan 40-80 mg was evaluated in 24 patients with mild-to-moderate hypertension and LVH. Patients were titrated to the higher dose of study drug at week 4 if they did not achieve blood pressure normalization (i.e. systolic blood pressure [SBP]/diastolic blood pressure [DBP] remained > or = 140/90 mmHg). The anti-hypertensive action of telmisartan was assessed using clinic cuff measurements and 24-h ambulatory blood pressure monitoring, and left ventricular mass index (LVMI) was determined by two-dimensional echocardiography at baseline and after 24 weeks of therapy. Telmisartan significantly reduced mean 24-h, daytime and night-time SBP and DBP compared with baseline after 12 and 24 weeks of therapy. Target blood pressure levels, defined as SBP/DBP < 140/90 mm Hg, were achieved in 16 (69.6%) patients at the end of the treatment period. After 24 weeks of telmisartan treatment, LVMI decreased from 151.6 +/- 5.4 to 135.1 +/- 5.9 g/m2. In conclusion, anti-hypertensive treatment with telmisartan for 24 weeks produced significant reductions in blood pressure and regression of LVH, as assessed by LVMI, in patients with hypertension and LVH.

[Cardiological aspects of the antiphospholipid syndrome. Part I. Valvular lesions in the primary and secondary antiphospholipid syndrome and systemic lupus erythematosus]. / Kardiologicheskie aspekty antifosfolipidnogo sindroma. Chast' I. Klapannye porazheniia serdtsa pri pervichnom i vtorichnom antifosfolipidnom sindrome i sistemnoi krasnoi volchanke.

AIM: To assess prevalence of cardiac valvular lesions in patients with primary (P) antiphospholipid syndrome (APLS) and systemic lupus erythematosus (SLE) with and without secondary APLS. MATERIAL AND METHODS: Patients with PAPLS (n=56, 15 men and 41 women), SLE and APLS (n=88, 23 men, 65 women) and SLE without APLS (n=51, 19 men, 32 women) were followed up for 9 years. Serological markers of APLS were anticardiolipin antibodies and lupus anticoagulant. RESULTS: Prevalence of various heart defects was the highest in PAPLS (43%) compared with SLE with APLS (c2=5.6, p=0.001) and SLE without APLS (c2=9.3, p=0.0002). In secondary APLS prevalence of valvular involvement was 27% what was substantially more than in SLE without APLS (4%) (c2=7.2, p=0.0007). Changes of mitral valve cusps and mitral regurgitation were found in 33, 41 and 50% of patients with SLE, SLE with APLS and PAPLS, respectively. Pronounced mitral regurgitation and valve defects were significantly more frequent in patients with any APLS compared with those with SLE without APLS. Thickening of aortic cusps was significantly more frequent in patients with PAPLS compared with patients with SLE (with and without APLS). Changes of tricuspid valve were significantly more frequent in patients with any APLS. Progression of valvular pathology was observed in 2 patients with SLE and APLS after 4 and 5 years of follow up. During 9 years thrombotic complications developed in 8 patients with APLS and valvular lesions (6 strokes, 2 retinal thromboses). CONCLUSION: An association exists between presence of APLS and various cardiac valvular lesions. Lesions of aortic valve are associated with PAPLS: Development of valvular pathology in patients with SLE and PAPLS during follow up dictates the necessity to monitor echocardiographical parameters and titers of anticardiolipin antibodies.

[Angiotensin II receptor blocker telmisartan: effect on 24-hour blood pressure profile and left ventricular hypertrophy in patients with hypertension]. / Blokator retseptorov angiotenzina II telmisartan: vliianie na sutochnyi profil' arterial'nogo davleniia i gipertrofiiu miokarda levogo zheludochka u bol'nykh arterial'noi gipertoniei

AIM: To study antihypertensive efficacy of monotherapy with telmisartan and its action on left ventricular myocardium remodeling in patients with hypertension. MATERIAL AND METHODS: Telmisartan (40-80 mg/day) was given for 24 weeks to 24 patients aged 37-69 years with I-II degree of blood pressure (BP) elevation and hypertrophy of left ventricular myocardium. Antihypertensive action of telmisartan was assessed by 24-hour BP monitoring. Left ventricular myocardial mass was estimated by echocardiography before and after 24 weeks of therapy. RESULTS: Telmisartan equally decreased both diurnal and nocturnal systolic and diastolic BP (by10.4-11.7%), lowered maximal BP during morning hours, and restored initially disturbed 24-hour BP rhythm. Target BP levels were achieved in 16 patients (70%). Therapy with telmisartan was associated with significant 10.9% reduction of left ventricular myocardial mass index (from 151.6-/+5.4 to 135.1-/+5.9 g/m2, p=0,02) at the account of decreased thickness of left ventricular wall. CONCLUSION: These results give reason for the use of telmisartan for the treatment of patients with hypertensive disease and left ventricular hypertrophy.

[Myocardial microcirculation in patients with systemic lupus erythematosus]. / Sostoianie mikrotsirkuliatsii miokarda u bol'nykh sistemnoi krasnoi volchankoi.

AIM: To examine myocardial microcirculation in patients with SLE. MATERIAL AND METHODS: Examination of 21 SLE patients consisted of perfusion tomoscintigraphy of the myocardium with Tl-201 at rest and in combination with bicycle exercise. Various protocols were used. RESULTS: The majority of SLE patients had resting disorders of myocardial perfusion: 5 had macrofocal scar lesion of the myocardium, 12 had disorders typical for small-focal myocardial fibrosis. Normal distribution of the perfusion occurred in 4 cases. Tomoscintigraphy performed in combination with exercise test revealed in 11 of 15 patients transient perfusion disturbances reflecting transient myocardial ischemia. One third of the patients had changes characteristic of myocardial ischemia due to coronary atherosclerosis. CONCLUSION: SLE patients have disorders of myocardial perfusion including those characteristic of scar lesion, small-focal cardiofibrosis and transient myocardial ischemia of different genesis: due to disorders in microcirculation and atherosclerotic lesion of major coronary arteries.

[Arterial hypertension and the antiphospholipid syndrome]. / Arterial'naia gipertoniia i antifosfolipidnyi sindrom.

Antiphospholipid syndrome (APLS) is defined as a symptom complex characterized by arterial and venous thromboses, obstetric abnormalities, thrombocytopenia and hyperproduction of antiphospholipid antibodies. APLS may be primary and secondary developing in the presence of autoimmune disorders, SLE in particular. At examination of 28 patients with primary and secondary APLS 14 patients proved hypertensive. Renal pathology was absent. Arterial hypertension appeared often in combination with microthrombi of the skin and affections of peripheral vessels. Arterial hypertension as a cardiological sign of APLS occurs more frequently than other symptoms.

[Involvement of cardiac valves in antiphospholipid syndrome]. / Osobennosti porazheniia klapanov serdtsa pri antifosfolipidnom sindrome.

Antiphospholipid syndrome (APLS) is a clinicolaboratory symptom complex characterized by development of venous and/or arterial thromboses, thrombocytopenia, obstetric pathology arising in the presence of hyperproduction of antiphospholipid antibodies (APAB). APLS may occur not only in patients with systemic lupus erythematosus (SLE) or other autoimmune diseases as secondary APLS, but in those without the above diseases as the primary APLS. The authors have examined 34 patients with APLS versus 10 patients with a verified SLE free of APLS manifestations. Affection of the valves was found in 30 patients with APLS (88%). More frequent were additional structures on mitral and aortic valve cusps, thickening of mitral valve cusps in APLS patients. Evident valvular disease was seen only in APLS patients with high positive levels of APAB. Valvular lesions were similar in patients with primary and secondary APLS. The study has revealed a relationship between the presence of antibodies to phospholipids and valvular abnormalities in APLS patients.

[The manifestations of IHD and the status of the coronary arteries in patients with the antiphospholipid syndrome]. / Proiavleniia IBS i sostoianie koronarnykh aterii u bol'nykh s antifosfolipidnym sindromom.

Of 20 patients with antiphospholipid syndrome 6 were found clinically and upon special tests to have signs of ischemic heart disease. All the 6 had shifts in lipid spectrum of plasma. It is important to study coronary pathology in antiphospholipid syndrome to elucidate mechanisms underlying thrombosis and vascular atherosclerosis in human diseases.