Nghiên cứu đặc điểm lâm sàng, nồng độ CRP, TNF α huyết thanh và biển đổi một số chỉ số hình thái, chức năng tim ở bệnh nhân viêm khớp dạng thấp tt tiếng anh

MINISTRY OF EDUCATION MINISTRY OF DEFENCE AND TRAINING VIETNAM MILITARY MEDICAL UNIVERSITY HOANG TRUNG DUNG STUDY ON CLINICAL CHARACTERISTICS, PLASMA CRP LEVEL, SERUM TNF-α AND AlTERATIONS OF SOME CARDIAC MORPHOLOIC AND FUNCTIONAL PARAMETERS IN RHEUMATOID ARTHRITIS PATIENTS Specialty : INTERNAL MEDICINE Code : 72 01 07 THE SUMMARY OF THE MEDICAL DOTORAL THESIS HANOI - 2019 THIS DOCTORAL THESIS WAS COMPLETED AT VIETNAM MILITARY MEDICAL UNIVERSITY Scientific Instructors: A/PROF Ph.D Doan Van De Ph.D Vien Van Doan 1st Contradictor: A/PROF PhD Le Thu Ha 2nd Contradictor: A/PROF PhD Phan Thi Thu Anh 3rd Contradictor: A/PROF PhD Nguyen Thi Phi Nga The doctoral thesis will be reported to The Grading and Examinations Committee hold at Vietnam Military Medical University at ….2018 Searching for the dissertation at: - National Library - Vietname Military Medical University’s library INTRODUCTION Rheumatoid arthritis (RA) is a chronic autoimmune arthritis In addition to joint destruction, it can damage the heart, lungs… This is a severe prognostic factor that can lead to death C Reactive Protein (CRP) is a protein produced in inflammatory response CRP level is also related to cardiovascular events The role of TNF-α (Tumor Necrosis Factor-alpha) in the pathogenesis of RA has been increasingly investigated TNF-α not only plays a role in evaluating the therapeutic response but is also a cardiovascular risk factor The leading cause of death in patients with RA is cardiovascular damage Cardiovascular manifestations of RA are often discreet If not detected early and treated promptly, heart damage will affect the quality of life and the risk of death of patients with RA One of the methods of comprehensive evaluation of cardiac dysfunction is Doppler ultrasonography Therefore, the thesis "Study on clinical characteristics, plasma CRP level, serum TNF-α and alterations of some cardiac morphologic and functional parameters in rheumatoid arthritis patients" was conducted with two objectives: To describe the clinical, subclinical features, plasma CRP level, serum TNF-α level and some cardiac morphologic and functional parameters in patients with rheumatoid arthritis To understand the relationship between clinical and subclinical characteristics, plasma CRP level, serum TNF-α level, level of disease activity with some cardiac morphologic and functional parameters in rheumatoid arthritis patients * The scientific significance This study investigated changes in plasma CRP level, serum TNF-α level and some cardiac morphologic and functional indexes of RA patients compared with that of control group and the association between some cardiac morphologic and functional parameters with clinical and subclinical characteristics * The practical significance This research shows that plasma CRP level and serum TNF-α level of RA patients were higher than that of the control group 35.2% of RA patients had left ventricular (LV) diastolic dysfunction (DD) The research reveals the relationship between some cardiac morphologic and functional parameters with clinical and clinical characteristics in patients with RA * New contributions of this doctoral thesis - This is the first scientific study in Vietnam researching Tissue Doppler Imaging (Doppler myocardial imaging) in RA patients - The study shows that serum TNF-α level of rheumatoid arthritis patients was higher than that of patients in the control group and there is no correlation between it and clinical and subclinical features - Even though patients had no clinical symptoms the results of the study shows that more than 35.2% of RA patients had left ventricular diastolic dysfunction and there is a strong correlation between Em at septal mitral annulus and disease duration and age Therefore, screening left ventricular diastolic function should be performed on patients with RA with a duration of more than years and patients aged over 60 years old * The doctoral thesis arrangement: This thesis contains 132 pages (without references and appendixes): Introduction: 02 pages, Chapter Overview: 34 pages, Chapter Subjects and methods: 25 pages, Chapter Results: 33 pages, Chapter Discussion: 34 pages, Conclusion: 02 pages, Recommendations: 01 page It includes 35 tables, 18 graphs, 10 figures, and 135 references (17 Vietnamese references and 118 English references) CHAPTER 1: OVERVIEW 1.1 Overview of rheumatoid arthritis 1.1.1 History of research RA is a systemic disease characterized by chronic inflammation of the synovial membrane The disease has been known since 1940 by Waaler 1.1.2 Clinical symptoms The common clinical symptoms include morning stiffness, symmetrical polyarticular joint swelling and pain in the hands, feet, wrists, ankles, elbows, knees, shoulders, groin RA can possibly lead to joint deformities of hands and feet in the later stages of the disease Common extra-articular manifestations: cardiac disease, pulmonary involvement, chronic anemia, subcutaneous nodules 1.1.3 Subclinical symptoms Elevated CRP level, elevated ESR, RF tests, anti-CCP, hand Xray, joint ultrasound, joint MRI 1.1.4 Diagnosis of rheumatoid arthritis Diagnosis of RA is based on the ACR 1987 criteria Recently, the ACR / EULAR 2010 criteria has been used to diagnose early RA 1.1.5 Evaluate the level of disease activity Evaluating level of disease activity plays an important role in the prognosis of RA and is the determinant factor (decision-making) in choosing appropriate treatment options In addition to the criteria: the number of painful and swollen joints, duration of morning stiffness, CRP concentration, erythrocyte sedimentation rate (ESR), ACR and EULAR recommend using DAS28 CRP, DAS28 ESR, CDAI, SDAI 1.1.6 Treatment of rheumatoid arthritis Internal medicine includes non-drug treatments and medication Medications include: anti-inflammatory medications - NSAIDs and glucocorticoids, analgesics and DMARDs There are two classes of DMARDs: non-bioactive DMARDs and biological DMARDs 1.2 Mechanism of pathogenesis and role of CRP, serum TNF-α 1.2.1 New view of the pathogenesis of rheumatoid arthritis RA is a chronic inflammatory autoimmune disease in which immune tolerance is broken causing to abnormal immune responses to antigens Genetic factors along with the environmental factors may activate the development of RA, activate T cell in synovial membrane via T-CD4 + Chronic inflammation of synovial membrane and destruction of articular cartilage are caused under the regulation of cells: T-CD4 +, Th1 and Th17, B lymphocytes, proinflammatory cytokines: TNF-α, IL-1, IL-6 , as the consequence, pannus formation and articular cartilages degradation lead to joint fibrosis, adhesion and deformity 1.2.2 C Reactive Protein CRP is a protein synthesized during inflammation CRP level are associated with a high risk of cardiovascular events in patients with RA Cardiovascular disease is a chronic inflammatory disease with the increase in level of inflammatory markers, especially CRP and TNF-α CRP affects the pathogenesis of atherosclerosis and endothelial dysfunction CRP activates arterial endothelium to cause atherosclerosis 1.2.3 Tumor necrosis factor alpha TNF-α is a proinflammatory cytokine that plays an important role in the pathogenesis of RA TNF-α not only stimulates the cells secreting it but also stimulates the production of other inflammatory cytokines such as IL-1, IL-6, IL-8 TNF-α regulates the balance between bone formation and bone turnover, causes arthritis and cartilage destruction TNF-α is involved in the pathogenesis of many cardiovascular diseases including atherosclerosis, myocardial infarction, cardiac failure, and myocarditis 1.3 Cardiac involvement and the role of Tissue Doppler Imaging (TDI) in cardiac morphologic and functional evaluation 1.3.1 Cardiac involvement in rheumatoid arthritis - Cause: inflammation induces CRP level, erythrocyte sedimentation rate, TNF-α, RF Due to the effects of medications: Glucocorticoid, NSAIDs, Methotrexatr, anti-TNF-α drugs - Cardiac involvement includes: pericarditis, cardiomyopathy, myocardial ischemia, amyloid cardiomyopathy, cardiac dysrhythmia, valvular heart disease - Mechanism of cardiac damage: T cells, T-CD4 +, T ‘CD28null’ 1.3.2 The role of Tissue Doppler Imaging in cardiac morphologic and functional evaluation - Left Ventricular Morphology Assessment on T mode: Measurements for Dd, Ds, IVSTd, IVSTs, LVPWD, LVPWs, LVM, EVD, ESV, FS, EF, CO - Doppler ultrasound: Measurements of E wave, A wave, E / A ratio, DT, IVCT, IVRT, ET - Left ventricular (LV) Tei index = (IVCT + IVRT) / ET - Tissue Doppler imagining at the interventricular septum and lateral mitral annulus: Measurements of Sm wave, Em wave, Am wave, E / Em ratio, Em / Am ratio 1.4 Domestic and foreign studies 1.4.1 Overseas studies According to Shrivastava A.K et al (2015) and Hanan M et al (2015): serum CRP, TNF-α levels were higher than that of the control group Wislowska M et al (2008), Sitia S et al (2012), Fatma E et al (2015): left ventricular morphologic indexes of RA patients and controls were the same There were changes in cardiac functions, especially left ventricular diastolic function in patients with RA compared with the control group Studies have shown that some cardiac function indexes correlate with age, duration of disease, plasma CRP level, serum TNF-α level in patients with RA 1.4.2 Studies in Vietnam Up to now, there have been no published studies on the role of TNFα and some morphological and cardiac indexes in Tissue Doppler Imaging and the association between some cardiac morphologic and functional indexes and clinical and subclinical characteristics CHAPTER 2: SUBJECTS AND METHODS 2.1 Subjects The study included 122 active RA patients and 51 healthy controls 2.1.1 Study group Inclusion criteria: - Diagnosed with RA based on American College of Rheumatology ACR 1987 criteria - No clinical manifestations of cardiovascular disease - Consent to participate in the study Exclusion criteria: - Patients with cardiovascular disease such as heart valve disease, congenital heart disease, valve regurgitation grade 2-4, cardiac arrhythmias - Patients with pneumonia, pulmonary tuberculosis, pleural effusion, infectious arthritis, diabetes mellitus, hypertension, scleroderma, systemic lupus erythematosus - Patients did not consent to participate in the study 2.1.1 Control group Inclusion criteria: - People at the same age and gender - No history of arthritis, cardiovascular disease and medical conditions - Consent to participate in the study Exclusion criteria: - Patients with definitive diagnosis or suspected cardiovascular disease: based on clinical findings and electrocardiogram: chest pain on examination, history of angina pectoris, history of diagnosed myocardial infarction, heart failure, cardiac arrhythmias Based on echocardiography: mitral stenosis and/or aortic valve stenosis and/or tricuspid stenosis at any grade, mitral regurgitation and/or aortic valve regurgitation and/or tricuspid regurgitation grade or more, left ventricular systolic dysfunction, regional wall motion dysfunction/abnormalities, interventricular septal thickness and/or left ventricle posterior wall thickness, left ventricular dilatation - Patients did not consent to participate in the study 2.1.3 Time and place This study was conducted from October 2014 and April 2018 at the Department of Rheumatology, Bachmai Hospital 2.2 Research Methods 2.2.1 Study Design: Prospective, descriptive cross-sectional study 2.2.2 Sampling method: p.q Sampling Size Formula: n = Z 1− a / 22 According to Liang K.P et al (2010) 31% of patients d with rheumatoid arthritis had left ventricular diastolic dysfunction Select p = 0.31 to form a sample size of at least 82 patients This study was conducted on 122 patients (n = 122) 2.2.3 Steps to conduct research Research subjects were examined clinically, the following investigations were done: laboratory tests, plasma CRP level, serum TNF-α level, Chest X-ray, Electrocardiography, Tissue Doppler Imaging - Patients with rheumatoid arthritis were examined clinically and assessed the level of disease activity: duration of disease, duration of morning stiffness, the number swollen joints, the number of pain joints, VAS scores, CDAI, SDAI, DAS28 CRP, DAS28 ESR - Complete Blood count (CBC), erythrocyte sedimentation rate (ESR) hr, hrs, rheumatoid factor (RF) - CRP level measurement by measuring turbidity on AU 5800 with Beckman Coulter test - TNF-α concentration measurement: using CLIA on the Immulite 1000 System from Siemens - Posterior-anterior chest X-ray - Electrocardiography - Tissue Doppler Imaging - Morphological assessment on echocardiography T mode: measurement of Dd, Ds, IVSTd, IVSTs, LVPWD, LVP, LVM, EVD, ESV, FS, EF, CO - Doppler echocardiography: Measurements of E wave, A wave, E/A ratio, DT, IVCT, IVRT, ET - Left ventricular index - Doppler ultrasound of at interventricular septum and lateral mitral annulus: Measurements of Sm, Em, Am, E/Em, Em/Am 2.2.4 Criteria used in research - Assessment of BMI according to the World Health Organization - Diagnosis of RA according to ACR 1987 - Assessment of clinical symptoms: duration of disease, duration of morning stiffness, the number of tender joins, the number of swollen joints, VAS score - Diagnosis of level of disease activity: DAS28 CRP - Diagnosis of anemia based on Hb concentration according to the World Health Organization - Diagnosis of left ventricular systolic dysfunction: EF% - Diagnosis of left ventricular diastolic dysfunction according to the American Society of Echocardiography 2009 2.2.5 Research parameters - Clinical parameters: age, sex, BMI, BSA, systolic blood pressure, diastolic blood pressure - Duration of disease: divided into groups: ≤ year; to years; ≥ years - Duration of morning stiffness: < 45 minutes; 45 to 60 minutes; > 60 minutes - The number of tender joints, the number of swollen joints - VAS scores (3 levels): 10 - 40; 50 - 60; 70 - 100 - CDAI, SDAI - DAS28 CRP: DAS28 CRP < 2.6; 2.6 ≤ DAS28 CRP ≤ 3.2; 3.2 ≤ DAS28 CRP ≤ 5.1; DAS28 CRP > 5.1 2.2.5.2 Sub-clinical parameters - Complete blood count, erythrocyte sedimentation rate 1hr, hrs - Diagnosis of anemia: Hb < 130 (g/L) in men and Hb < 120 (g/L) in women Classification: Hb > 110 (g/L): mild anemia; Hb: 80 - 109 (g/L): moderate anemia; Hb < 80 (g/L): severe anemia - Immunological tests: RF concentration (IU / mL) Evaluation: RF < 14 IU/mL: negative; 14 IU/mL ≤ RF ≤ 42 IU/mL: low positive; RF > 42 IU/mL: high positive 2.2.5.3 Assessment of inflammation level Measure plasma CRP level (mg/dL) Measure serum TNF-α level (pg/mL) 2.2.5.4 Tissue Doppler Imaging - Parameters for cardiac morphology: + Left ventricular end-diastolic diameter (Dd - mm) + Left ventricular end-diastolic diameter (Ds - mm) + Interventricular septal end diastole thickness (IVSd - mm) + Interventricular septal end systole thickness (IVSs - mm) + Left ventricular posterior wall end diastole thickness (LVPWd mm) + Left ventricular posterior wall end systole thickness (LVPWs mm) + Left Ventricular Mass (LVM - g) - Left ventricular systolic function indexes: + End Diastolic Volume (EDV - ml) + End Systolic Volume (ESV - ml) + Cardiac output (CO - l/ph) + Fraction Shortening (FS%) + Ejection Fraction (EF%) - Left ventricular diastolic function indexes: + Transmitral early diastolic peak velocity (E - cm/s) + Transmitral late diastolic peak velocity (A - cm/s) + E/A ratio + Deceleration Time (DT - ms) + Isovolumetric relaxation time (IVRT - ms) + Left ventricular Tei index - Tissue Doppler Imaging at interventricular septum and lateral mitral annulus: + Peak systolic velocity (Sm - cm/s) + Peak early diastolic velocity (Em - cm/s) + Peak late diastolic velocity (Am - cm/s) + E/Em ratio 11 DAS28 ESR 6.35 ± 0.89 6.54 3.50 – 8.11 Table 3.3 Duration of disease from to years accounted for 48.4%, over years represented 35.2% Duration of morning stiffness from 45 to 60 minutes and over 60 minutes accounted for 45.9% and 34.4%, respectively Patients with severe pain (VAS score 70 – 100) made up 61.2% Table 3.3 Regarding DAS28 CRP, there were 74.6% of patients with high disease activity and 23.8% of patients with moderate disease activity 3.1.2 Sub-Clinical characteristics of patients with rheumatoid arthritis Table 3.4 and 3.5 Median ESR hr and hrs were high There were 25.4% of patients with anemia including 16.4% of patients with mild anemia and 9.0% of patients with moderate anemia Table 3.6 RF concentration was 85.73 ± 73.74 High positive rate was 63.1% 3.1.3 Concentration of plasma CRP level, serum TNF-α level of study subjects Table 3.7 Characteristics of plasma CRP level, serum TNF-α level Rheumatoid arthritis Control group p Index (n = 122) (n = 51) 2.56 ± 2.81 0.12 ± 0.12 < 0.01 Plasma CRP level 1.77 (0.02 – 14.64) 0.08 (0.01 – 0.50) (mg/dL) Serum TNF-α, 15.32 ± 7.37 8.84 ± 2.17 < 0.01 level (pg/mL) 13.70 (6.22 – 38.50) 9.18 (4.51 – 12.90) Plasma CRP level and serum TNFα level of RA patients were higher than that of control group, p 0.05 12 Table 3.9 There was no difference between median TNF-α serum concentration in patients with DAS28 CRP> 5.1 and that of patients with DAS28 CRP ≤ 5.1 (p> 0.05) Table 3.10 Serum TNF-α level was not correlated with: the number of tender joints, the number of swollen joints, duration of morning stiffness, plasma CRP level, ESR 1hr, DAS28 CRP, DAS28 ESR, p > 0.05 3.1.4 Some cardiac morphologic and functional parameters study subjects Table 3.11 Some indexes of left ventricular morphology and systolic function of RA patients and control group were similar, p > 0.05 IVSd, IVSs and LVPWs of RA patients were higher than that of control group, p < 0.05 Table 3.12 Wave A in RA patients was higher than that of the control group, p < 0.01 There was no difference between Tei index of RA patients and of control group, p > 0.05 E/A ratio and IVRT of RA patients were lower than that of the control group, p < 0.05 Table 3.13 Tissue doppler imaging at the interventricular septum: Em of RA patients was lower than that of the control group, p < 0.05 Em/Am ratio in study group was lower than that of the control group, p < 0.01 There was no difference in Sm, Am and E/Em ratio of study subjects and controls, p > 0.05 Tissue Doppler Imaging at lateral mitral annulus: Em and Em/Am ratio of RA patients were lower than that of the control group, p < 0.05 There was no difference in Sm, Am and E/Em ratio of study subjects and controls, p > 0.05 Table 3.14 and 3.15 The rate of left ventricular diastolic dysfunction in RA patients was 35.2% which was higher than that of the control group, at 17.7% (p < 0.01) Among 35.2% of patients with rheumatoid arthritis who had left ventricular diastolic dysfunction, the proportion of patients with left ventricular diastolic dysfunction grade I, II, III were 16.4%, 18.0, and 0.8%, respectively 3.2 The relationship between clinical, subclinical characteristics, plasma CRP level, serum TNF-α level, level of disease activity with some cardiac morphologic and functional parameters in RA patients 3.2.1 The association between clinical, subclinical characteristics, plasma CRP level, serum TNF-α level, level of disease activity with some left ventricular morphologic indexes 13 Table 3.16 IVSd, IVSs and LVPWd values were positively correlated to age and duration of disease EF and FS indexes were in inverse proportion to DAS28 CRP Table 3.17 IVSd, IVSs, LVPWd, LVPWs and LVM were positively correlated to RF level EF and FS indexes were negatively correlated to plasma CRP levels IVSs and LVPWd were positively correlated to serum TNF-α level 3.2.2 The relationship between clinical features with cardiac function indexes * The relationship between cardiac function indexes and age Table 3.18 A wave of patient < 60 years old was lower than A wave of patients ≥ 60 years old, p < 0.05 E/A ratio in patients < 60 years was higher than that of patients≥ 60 years old, p < 0.05 There was no difference in left ventricular Tei index in < 60 years and patients ≥ 60 years old, p > 0.05 Figure 3.4 and 3.5 There was positive correlation between A wave, IVRT and left ventricular Tei score, meanwhile, E / A ratio was negatively correlated to the age of RA patients, p < 0.01 Table 3.19 Tissue doppler imaging at the interventricular septum and lateral mitral annulus: Em and Em/Am ratio of patients < 60 years were higher than that of patients ≥ 60 years, p < 0.05 Am index of patients < 60 years was lower than that of patients≥60 years, p < 0.01 Figures 3.6, 3.7, 3.8, and 3.9: Tissue doppler imaging at the interventricular septum and lateral mitral annulus: there was negative correlation between of Em index and E/Em ration, meanwhile Am index and E/Em ratio were positively correlated to patient age, p < 0.01 * The association between cardiac function indexes and duration of disease Table 3.20 There was no difference between E wave and A wave in patients with disease duration ≤ year and those with disease duration> year, p> 0.05 Figures 3.10 and 3.11: E wave was negatively correlated E/A ratio; meanwhile, there was positive correlation between A wave, IVRT and duration of disease, p < 0.05 Table 3.21 Tissue doppler imaging at the interventricular septum and mitral annulus: in RA patients, the longer duration of disease was, the higher E/Em ratio was, meanwhile Sm, Em, and Em/Am 14 ratio decreased, p < 0.01 Tissue doppler imaging at lateral mitral annulus: Patients with RA had a longer duration of disease, Em index and Em/Am ratio decreased, p < 0.01 Figure 3.12 There was a correlation between the Sm and Em indexes at the interventricular septum and mitral annulus with disease duration, p < 0.001 Figures 3.13 and 3.15 At the interventricular septum and lateral mitral annulus E/Em ratio was positively correlated with duration of disease, in contrast to Em/Am ratio which was negatively correlated to disease duration, p < 0.001 Figure 3.14 At lateral mitral annulus, there was negative between Em index and duration of disease, p < 0.001 Meanwhile, Am index was positively correlated to disease duration p < 0.001 3.2.3 The association between subclinical features and some cardiac function indexes: Table 3.22 E/A ratio was negatively correlated to RF concentration, p < 0.05 Table 3.23: There was negative correlation between Em at interventricular septum and mitral annulus and RF concentration E/Em ratio at lateral mitral annulus was negatively correlated to Hb concentration 3.2.4 The relationship between plasma CRP level, serum TNFα level and cardiac indexes 15 Table 3.24 There was positive correlation between plasma CRP level and left ventricular Tei index, r = 0.283; p < 0.05 Table 3.25 There was no relation between plasma CRP concentration and Tissue Doppler Imaging indexes at interventricular septum and mitral annulus, p> 0.05 Figure 3.16 There was positive correlation between plasma CRP level and Am index at lateral mitral annulus, p < 0.05 Table 3.26 and 3.27 There was positive correlation between serum TNF-α level and DT, and E/Em ratio at interventricular septum and mitral annulus There was negative correlation between Em, Em/Am interventricular septum and mitral annulus, and E/Em at lateral mitral annulus, p < 0.05 Figure 3.17 and 3.18 There was negative correlation between Em index, Em/Am ratio at interventricular septum and mitral annulus, Em at lateral mitral annulus E/Em ratio at lateral mitral annulus was negatively correlated to serum TNF-α level, p < 05 3.2.5 The relationship between level of disease activity and cardiac function indexes Table 3.28 Mitral valve Tissue doppler imaging: there was no difference between E wave and E/A ratio of RA patients with DAS28 CRP > 5.1 and that of those with DAS28 CRP ≤ 5.1, p > 0.05 Table 3.29 Tissue doppler imaging at the interventricular septum and lateral mitral annulus: there was no difference between Em, E/Em, and Em/Am in RA patients with DAS28 CRP > 5.1 and that of RA patients with DAS28 CRP ≤ 5.1, p > 0.05 Tables 3.30 and 3.31 DAS28 CRP index was not correlated with mitral valve Doppler echocardiography indexes, left ventricular Tei index and Tissue doppler imaging at the interventricular septum and lateral mitral annulus indexes, p > 0.05 16 Table 3.32 The relationship between left ventricular diastolic dysfunction and DAS28 CRP Index Diastolic function No diastolic Total (n = 43) dysfunction n DAS28 (n = 79) CRP ≤ 5.1 11 20 31 > 5.1 32 59 91 Total 43 79 122 OR = 0.986 (CI 95%: 0.421 – 2.313); χ²; 0.001; p = 0.974 There was no difference in risk of left ventricular diastolic dysfunction between patients with DAS28 CRP > 5.1 and those with DAS28 ≤ 5.1, OR = 0.986 (CI 95%: 0.421 - 2.313), p = 0.974 CHAPTER 4: DISCUSSION 4.1 Clinical, subclinical characteristics, plasma CRP level, serum TNF-α level and some cardiac morphologic and functional parameters in patients with rheumatoid arthritis 4.1.1 Clinical characteristics of patients with rheumatoid arthritis Age, gender, systolic blood pressure, diastolic blood pressure of study subjects were similar to that of controls, p > 0.05 Height, weight, BMI, BSA of study subjects were lower than the data of controls, p < 0.05 Duration of disease was 5.37 ± 5.25 years Duration of morning stiffness was 61.48 ± 27.64 (minutes) The number of swollen joints was 9.95 ± 3.71, the number of tender joints was 13.30 ± 4.34 VAS score was 67.38 ± 11.49 DAS28 CRP was 5.77 ± 0.94 4.1.2 Sub-Clinical characteristics of patients with rheumatoid arthritis Hb concentration was 129.44 ± 14.32 (g/L) 25.4% of RA patients had anemia Among anemic RA patients, the proportions of mild anemia and moderate anemia were 16.4% and 9%, respectively 17 RF level was 85.73 ± 73.74 (IU/mL), the percentages of patients with negative RF, low-positive RF, and high-positive RF were 24.6%, 12.3%, 63.1%, respectively 4.1.3 Concentration of plasma CRP levels, serum TNF-α levels of study subjects Plasma CRP level of patients was 2.56 ± 2.81 (mg/dL) which was higher than that of controls, 0.12 ± 0.12 (mg/dL) (p 5.1, serum TNF-α of 16.02 ± 7.50 (pg/mL), median of 14.10 and those who had DAS28 CRP ≤ 5.1, serum TNF-α level 13.26 ± 6.64 (pg/mL), median of 11.30 (p > 0.05) Our results are consistent with findings of Beyazal M.S et al (2017) Serum TNF-α level was not correlated to the number of tender joints, the number of swollen joints, duration of morning stiffness, plasma CRP concentration, ESR 1hr, DAS28 CRP and DAS28 ESR 4.1.4 Some cardiac morphologic and functional parameters study subjects 4.1.4.1 Some left ventricular morphologic indexes and systolic function of study subjects Dd, Ds, LVPWd, and LVM of study subjects were similar to that of controls, p > 0.05 IVSd, IVSs and LVPWs of RA patients in this study were higher than that of controls, p < 0.05 There was a 18 similarity between EF%, FS%, EDV, ESV, CO of study subjects and of controls, p > 0.05 Our results are consistent with findings of Muizz A.M et al (2011), Udayakumar N et al (2007), Rexhepaj N et al (2006) 4.1.4.2 Some cardiac function indexes of study subjects RA patients had significant left ventricular diastolic dysfunction that was illustrate by E/A ratio E/A ratio of RA patients was 1.02 ± 0.35 which was lower than that of controls, 1.11 ± 0.28 (p < 0.05) A wave of study subjects was 71.44 ± 15.84 (cm/s) which was higher than A wave of controls, 64.82 ± 12.41 (cm/s) (p < 0.01) Our results are consistent with findings of Fatma, E et al (2015) DT index of patients was 162.93 ± 49.79 (ms) which was lower than DT index of controls, 184.49 ± 37.51 (ms) (p 0.05 Tissue doppler imaging at the interventricular septum and mitral annulus: There was no difference between Sm wave of subjects (8.26 ± 1.56 (cm/s)) and of controls (8.09 ± 1.22 (cm/s)), p> 05 E wave of patients was 9.44 ± 2.91 (cm/s) which was lower than that of controls (10.23 ± 2.42 (cm/s)), p 0.05 There was no difference between E/Em of study research (7.82 ± 2.03) and controls 7.03 ± 1.43 with p > 0.05 Em/Am ratio of RA patients was 1.01 ± 0.48 which was lower than that of controls (1.17 ± 0.45), p < 0.01 Our results are consistent with findings of Fatma E et al (2012), Wislowska M et al (2008), Birdane A et al (2007) and Arslam S et al (2006) Tissue doppler imaging at lateral mitral annulus: there was no difference between Sm wave of study subjects which was 9.83 ± 2.49 (cm / s) and that of controls (9.20 ± 2.27 (cm / s)), p> 0.05 E wave of RA patients was 12.77 ± 3.98 (cm / s) which was lower than that of controls, 13.94 ± 3.69 (cm / s), p < 0.05 There was no difference between Am wave of patients, which was 10.83 ± 2.84 (cm / s), and Am wave of controls, 10.23 ± 2.64 (cm / s), p > 0.05 E/Em ratio of 19 patients was 5.85 ± 2.09 which did not differ from from that of controls, 5.02 ± 1.39 (p > 0.05) Em/Am ratio of subjects was 1.29 ± 0.61 which was lower than that of controls, 1.48 ± 0.57 (p < 0.05) Our results are consistent with findings of Sitia S et al (2012) and Birdane A et al (2007) * The rate of left ventricular diastolic dysfunction 35.2% of patients with RA had left ventricular diastolic dysfunction which was higher than the proportion of people who had left ventricular diastolic dysfunction in the control group, 17.7% (p < 0.05) There percentages of patients with grade I, II, and III left ventricular diastolic dysfunction were 16.4%, 18.0%, and 0.8%, respectively Our results are consistent with findings of Liang K.P et al (2010), Fatma E et al (2015), Gonzalez-Juanatey C et al (2004) 4.2 The relationship between clinical, subclinical characteristics, plasma CRP level, serum TNF-α level, level of disease activity level and some cardiac morphologic and functional parameters in patients with RA 4.2.1 The relationship between clinical, subclinical characteristics, plasma CRP level, serum TNF-α level, level of disease activity level and some morphologic indexes of left ventricle IVSd (r = 0.39, r = 0.39, p