Introduction___________________________

Rheumatoid arthritis (RA) is a systemic disorder associated with the involvement of several organs. The prevalence rate of this disease is about 1-2%, and it is 2.5 times more common in women than men. Aging is reported to increase the prevalence of RA and its complications [1,2]. According to various studies, cardiovascular diseases are the main causes of mortality in patients with RA, the risk of which doubles with aging [2]. Megha Prasad et al. demonstrated that the high risk of cardiovascular problems in patients with RA is independent from the known risk factors for cardiovascular diseases [1]. Common cardiovascular problems of RA patients include pericarditis, atherosclerosis, myocarditis, congestive heart failure, and heart block; RA patients are also at high risk for valve involvement due to chronic valvulitis [2-4].

Patients with RA are at high risk for cardiovascular involvement, and those diagnosed with this disease have a high mortality rate. Therefore, any measure that can facilitate the early detection of cardiovascular injuries before the occurrence of symptoms can reduce mortality and morbidity in RA patients. RA has a high prevalence in middle-aged women who are especially at risk of cardiovascular problems and coronary involvement due to menopause. Therefore, early diagnosis of cardiovascular disorders can prevent the progress of associated damage and decrease the mortality rate in this population [1, 4]. Given the limited number of studies on the use of the new diagnostic modalities, Doppler echocardiography and tissue Doppler imaging (TDI), in RA, the current study aimed to evaluate cardiovascular disorders in patients suffering from RA using these techniques.

Materials and Methods_________________

This descriptive, cross-sectional study was conducted on 40 RA patients [2-4] who referred to the Rheumatology Department and Clinic of Ghaem Hospital, affiliated with Mashhad University of Medical Sciences, Mashhad, Iran. RA was diagnosed based on the American College of Rheumatology criteria. In total, 40 patients with no clinical cardiovascular symptoms and normal electrocardiography (ECG), chest examination, and chest radiography results were entered into the study and investigated for six months. All patients were taking prednisolone, methotrexate, and hydroxychloroquine. Within this period, all necessary information was collected for further evaluation, and a complete rheumatology and cardiovascular assessment was carried out for each participant. Patients with a minimum of five years since their RA diagnosis and those without any cardiovascular diseases were included in the study. Exclusion criteria included a history of cardiac infarction or cerebrovascular problems (e.g., cerebrovascular accidents), any history of cardiac disease in the medical records, abnormal electrocardiography findings, and abnormal heart radiologic findings. Patients were subjected to electrocardiography, chest radiography, echocardiography (M-mode 2D), Doppler ultrasound, and tests of erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, and anti-cyclic citrullinated peptide. Subsequently, the subjects’ cardiac information was recorded.

The initial cardiovascular examination of the patients included history taking, a complete physical examination, electrocardiography, and chest radiography. All participants were evaluated with transthoracic echocardiography and tissue Doppler imaging using the GE Vivid 3 Dimensions ultrasound system (GE Healthcare, USA) with a 2.5-3.5 MHz probe in the left lateral decubitus position based on the guidelines of the American Society of Echocardiography and the European Association of Cardiovascular Imaging. All evaluations were recorded for further review. Different echocardiographic parameters were evaluated, including left ventricular systolic function, ejection fraction (EF), ventricular wall motion abnormalities, left ventricular diastolic function and its related parameters, early E-wave and end A-wave diastolic velocities, as well as E-wave deceleration time (DT). These estimations were accomplished by the placement of the Doppler probe on the lateral wall and interventricular septum and the assessment of the mean parameters of TDI, including systolic velocity (Sm) as well as early- and end-diastolic velocities (Am). Additionally, the right upper pulmonary vein blood flow was determined by the insertion of the Doppler probe on the vein, which also facilitated the estimation of systolic (S) and diastolic (D) wave velocities and reversed end-diastolic flow (Ar). Simultaneously, the left ventricular systolic and diastolic volumes, stenosis and insufficiency of each valve, pulmonary arterial pressure (PRP), tricuspid valve regurgitation velocity, the lack or presence of cardiomyopathy, and pericardial fluid were also assessed.

Statistical analysis

To analyze the data, values related to the echocardiographic variables, such as the diastolic, systolic, and TDI performance, end-systolic and -diastolic volumes, as well as stenosis and insufficiency status of each valve, were entered into SPSS version 11.5. The demographic characteristics (e.g., age and gender) and other variables such as ECG and chest X-ray findings were also recorded. Moreover, PRP was entered as a quantitative variable and then added as a qualitative variable after considering the cut-off point of 30. Data analysis was performed using the Chi-square, Fisher’s exact, and Mann-Whitney U tests as well as the Pearson’s correlation coefficient. The Kolmogorov-Smirnov test was applied to control the assumptions of parametric tests. A p-value less than 0.05 was considered statistically significant.

Results_______________________________

In total, 40 patients with RA were evaluated in this study for cardiovascular conditions. According to the results, the mean age of the patients was 46.4±15.48 years (age range: 20-80 years). The evaluation of age distribution based on 10-year age groups revealed that the highest frequency was related to the age range of 30-39 years (Table 1). The most common valvular abnormality in the patients was insufficiency of the tricuspid and mitral valves. Out of 29 patients with tricuspid insufficiency, 1, 1, and 27 subjects had severe, medium, and weak insufficiency, respectively. In addition, 20 out of 21 cases had weak mitral insufficiency, and one patient had medium regurgitation in this regard (Table 2). While 28 (70%) subjects had normal diastolic cardiac function, 1 (2.5%) and 11 (27.5%) cases had grades II (pseudonormal) and I (loose defect) diastolic dysfunction, respectively. Neither grade III diastolic dysfunction (restrictive) nor left ventricular wall motion abnormalities were observed in any of the patients.

Echocardiographic evaluations revealed no cardiac wall motion abnormalities in the patients. The parameters related to mitral valve in Doppler echocardiography and TDI of the right upper pulmonary vein are presented in Table 3. The mean cardiac EF was 61.27±4.80 with a minimum and maximum of 50 and 70, respectively. In addition, the results of the Pearson’s correlation coefficient were indicative of a significant positive relationship between Sm and cardiac EF (r=0.398, P=0.011). Regarding the relationship of TDI parameters with A and E mitral parameters and diastolic and systolic vein flows, the results of the Pearson correlation coefficient revealed no significant association between Em and E (r=0.128, P=0.432). Moreover, no significant relationship was observed between Am and A (r=0.032, P=0.844). However, there were direct correlations between Em and D (r=0.589, P=0.001) as well as between Sm and S (r=0.322, P=0.043). The investigation of the relationship between diastolic function and EF revealed that the mean EF values were 62.4±4.04 and 58.3±5.64 in the group with normal diastolic performance and patients with diastolic dysfunction, respectively.

Due to the non-normality of data distribution, the Mann-Whitney U test was run to compare the two groups, and the results demonstrated a significant difference between in EF values of the study groups (P=0.047). EF was significantly lower in the group with diastolic dysfunction compared with the group with normal diastolic function. The mean PRP was 72.53±5.73 mmHg, varying within 18-40 mmHg. Considering the cut-off point of 30 mmHg for PRP, this measure was < 30 mmHg in 24 (60%) patients and ≥ 30 mmHg in 16 (40%) cases. Moreover, PRP level was significantly associated with age (P=0.031). Those patients diagnosed with pulmonary hypertension were specifically older than those with normal PRP (Table 3).

Based on the results, there were no statistically significant differences in the frequency of various levels of frequency and diastolic dysfunction in age groups of below and above 45 years (P=0.343).

Table 1. Frequency distribution of valvular disorders in patients with rheumatoid arthritis based on age groups

Table 2. Frequency distribution of valvular disorders in patients with rheumatoid arthritis

Table 3. Results of Doppler echocardiography and tissue Doppler imaging in evaluation of parameters related to mitral valve and right upper pulmonary vein in patients with rheumatoid arthritis