Subclinical diastolic dysfunction and its association with disease activity in patients with rheumatoid arthritis

Subclinical diastolic dysfunction and its association with disease activity in patients with rheumatoid arthritis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Subclinical diastolic dysfunction and its association with disease activity in patients with rheumatoid arthritis Christiane Aguiar Nobre, CARLOS EWERTON MAIA RODRIGUES, Luzia Keyne Sousa Carneiro Frota, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8090949/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 4 You are reading this latest preprint version Abstract Rheumatoid arthritis (RA) is a chronic inflammatory disorder associated with cardiovascular risk (CVR), regardless of traditional risk factors. In this study we investigated the association between disease activity, CVR and cardiac and carotid ultrasound (US) findings in 60 RA patients and 60 age and sex-matched healthy controls. The clinical variables included epidemiological and laboratory data and disease activity scores (DAS28-PCR). CVR was stratified using SCORE/mSCORE and Framingham scores. The US methods employed (transthoracic echocardiography and Doppler carotid ecography) allowed to evaluate carotid intima-media thickness (CIMT), atherosclerosis plaque, and cardiac function. The female sex was predominant (RA = 91.7%; controls = 90%) and the mean age was 52 ± 12 years and 52 ± 13 years, respectively. The mean disease duration was 10.43 ± 7.55 years. Serum testing for rheumatoid factor and anti-CCP was double-negative in 36.7%. The DAS28-PCR scores identified 61.7% as ‘remission/low activity’ and 31.3% as ‘moderate/high activity’. CVR was similar in the two groups ( p = 0.261). When the echocardiographic data was stratified, diastolic dysfunction was significantly more prevalent in subjects with higher disease activity ( p = 0.04). In addition, high clinical CVR scores were associated with greater CIMT and carotid plaque ( p < 0.05). Our results suggest that inflammatory activity may play a major role in subclinical cardiovascular dysfunction in RA. Rheumatoid arthritis Disease activity Cardiovascular risk Ultrasonography Echocardiogram Subclinical diastolic dysfunction Introduction A chronic inflammatory condition affecting the joints, rheumatoid arthritis (RA) is considered an independent cardiovascular risk factor (CVRF) [ 1 , 2 ]. As shown in the literature, RA patients are at a significantly higher risk of cardiovascular events and mortality than the general population [ 3 , 4 ], mostly due to persistent systemic inflammation. Disease activity in patients with RA is directly related to cardiovascular risk, and this risk is proportional to the intensity and persistence of systemic inflammation, which contributes to endothelial dysfunction, lipid alterations, and a higher prevalence of subclinical atherosclerotic plaques [ 5 – 7 ]. The repercussion of RA on the cardiovascular system are multifaceted and generally involve structural and functional changes to the heart[ 8 – 10 ]. Functional changes often include diastolic dysfunction and reduced ejection fraction [ 11 , 12 ]. An understanding of the negative impact of cardiovascular disease (CVD) on overall health, quality of life and life expectancy, as well as of the early detection of subclinical signs, is essential for risk stratification and management of RA patients. Ultrasonography (US) is usually employed to this end, but the ideal method has not yet been established [ 13 ]. US modalities like transthoracic echocardiography and Doppler carotid ecography are low-cost, non-invasive and sensitive tools in cardiovascular screening [ 9 , 14 ]. In fact, a study on 104 RA patients found carotid US to be more sensitive than coronary artery calcium scores in the detection of subclinical atherosclerosis in RA [ 15 ]. The combination of traditional clinical scores with cardiac and carotid imaging methods is recommended to enhance cardiovascular risk assessment. The populations that benefit most from integrating traditional clinical scores with cardiac and carotid imaging methods for cardiovascular risk assessment are asymptomatic adults classified as low to intermediate risk by traditional scores (such as Framingham, SCORE), particularly those aged 40 to 65 years, without known cardiovascular disease[ 16 – 18 ]. In view of the known association disease activity in patients with RA and increased CVRF, the clinical benefit of early risk stratification, this study we evaluated the association between disease activity and subclinical diastolic dysfunction in RA in Northeastern Brazil. Methods Patients This cross-sectional study was conducted at a secondary-level health care facility in Northeastern Brazil between October 2021 and October 2022. The study protocol complied with the principles of the Declaration of Helsinkki [ 19 ] and was approved under #10729/2020 by the research ethics committee of the Federal University of Ceará (CEP/UFC/PROPESQ). All procedures followed well-established research standards and guidelines, and all participants gave their informed written consent prior to entering the study. The sample consisted of 120 participants, of which half were RA patients and half were sex and age-matched healthy controls recruited from the local community. All RA patients met the 2010 diagnostic criteria of the American College of Rheumatology[ 20 ]. The exclusion criteria were age under 18 years, pregnancy, previously diagnosed CVD, chronic kidney failure, and association with collagen disorders such as systemic lupus erythematosus, Sjögren syndrome, inflammatory myopathy, and sclerodermia. Sample size calculation The sample size was calculated considering carotid intima-media thickness (CIMT) as primary variable outcome. In an earlier study [ 21 ], patients with recent-onset RA had an average CIMT of 0.64 ± 0.13 mm, compared to 0.58 ± 0.09 mm in healthy controls. Based on this expected difference, we estimated that a statistical power of 80% at the 5% level of significance (α = 0.05) would require at least 55 participants per group. In this study, each group included 60 subjects, matching the design adopted in another cross-sectional study [ 22 ]. Clinical and anthropometric evaluation The collected information included epidemiological, clinical and laboratory data, such as blood count, C-reactive protein, rheumatoid factor (RF), anti-cyclic citrullinated peptide antibody (anti-CCP), glycemia, total cholesterol, high-density lipoprotein (HDL-c), low-density lipoprotein (LDL-c), and triglycerides. The 10-year cardiovascular risk was assessed using the systematic coronary risk evaluation (SCORE), the modified SCORE (mSCORE), and the Framingham score [ 23 , 24 ]. To calculate mSCORE, we multiplied the SCORE index by 1.5 in RA patients meeting at least 2 of the following 3 criteria: disease duration > 10 years, positivity for FR and/or anti-CCP, and extra-articular manifestations [ 25 ]. Upon physical examination, information was collected on the number of painful and swollen joints, arterial blood pressure, waist circumference (WC), and body-mass index (BMI). WC was measured with a tape positioned horizontally between the iliac crest and the lowest rib. BMI was calculated by dividing the weight by the height squared (kg/m²). Overweight was defined as BMI 25.0-29.9 kg/m² and obesity was defined as ≥ 30.0 kg/m². Disease activity was scored with the composite index DAS28-CRP, using the following interpretation: 5.1 = high activity [ 26 ]. Ultrasound evaluation Both groups of participants were submitted to cardiac and carotid US by a cardiologist (LKSCF) trained and experienced in the respective US techniques. Carotid US in B-mode with spectral Doppler allowed to conduct a morphological and hemodynamic analysis, with emphasis on CIMT measurement and the detection of atherosclerosis plaque―a well established marker of subclinical atherosclerosis [ 27 , 28 ]. Cardiac function was evaluated by 2-dimensional transthoracic echocardiography while the left ventricle ejection fraction (LVEF) was determined with the Teicholz method, following the guidelines of the American Society of Echocardiography [ 29 ]. Statistical analysis Clinical and demographic variables, when quantitative and continuous, were expressed as means ± standard deviation (SD) and medians + interquartile range, or, when categorical, as absolute numbers (n) and percentages (%). The main groups (RA vs. controls) and the CVRF subgroups were compared with the chi-squared test (categorical variables) or the Mann-Whitney and Kruskal-Wallis test (non-parametric and continuous variables). All statistical analyses were performed with the software SPSS v. 26.0 (IBM Corp., Armonk, NY, USA) at the 5% level of significance ( p < 0.05). Results The female sex was predominant in both the RA group (91.7%) and the control group (90%). The mean age was 52 ± 12 years and 52 ± 13 years, respectively. In the case-control analysis, when comparing the groups with regard to traditional CVRFs (family history of CVD, current or previous smoking, arterial hypertension, diabetes mellitus, sedentary lifestyle, systolic and diastolic blood pressure, total cholesterol, HDL and LDL), no significant difference was observed ( p > 0.05). Likewise, the two groups were statistically similar with regard to IMC and the distribution of low weight, overweight and obesity, but the prevalence of dyslipidemia was significantly higher in the control group (55.0%) than in the RA group (33.3%) ( p = 0.027). Moreover, the controls displayed higher WC (91.67 cm vs. 87.65 cm; p = 0.017) and BMI values (28.58 vs. 26.83; p = 0.010). As for laboratory parameters, the controls had significantly higher levels of glycemia (109.95 mg/dL vs. 93.92 mg/dL; p 10 years = 51.7%. The mean time since diagnosis was 8.57 ± 6.84 years. Positivity for either RF or anti-CCP was 20%, for both 43.3%, and for neither 36.7%. According to the DAS-28 PCR scoring system, 61.7% were classified as remission or low activity. The remainder (31.3%) had moderate or high activity. With regard to therapy, 59 of the 60 patients (98.3%) were treated with disease-modifying antirheumatic drugs (DMARDs), primarily csDMARDs (n = 55; 91.7%) used alone (n = 39; 66.1%) or in combination with biological DMARDs (n = 13; 22.0%) or targeted DMARDs (n = 7; 11.9%). Current use of corticosteroids was reported by 26.7%, while methotrexate was used by 72.9%. Table 1 shows the CVRFs of participants with and without RA expressed in SCORE/mSCORE and Framingham scores. According to the SCORE/mSCORE index, low risk was assigned to 45% of the RA patients and to 55.4% of the controls. Moderate risk was higher among RA patients (55% vs. 44.6%), but the difference was not significant ( p = 0.261). The mean Framingham score was slightly higher in the control group (8.34 ± 8.95%) than in the RA group (6.33 ± 6.78%), though not significantly ( p = 0.208). When arranged by category, low CVR (≤ 10%) was assigned to 68.3% of the controls and to 85% of the RA patients. Moderate risk (10–20%) and high risk (≥ 20%) were less frequent in the RA group, though not significantly. Cardiac and carotid US findings were statistically similar in the two groups with regard to CVR parameters (Table 1 ). Table 1 Cardiovascular risk factors (CVRFs) determined by ultrasound scanning of subjects without (controls) and with rheumatoid arthritis (RA). Variables Controls (n = 60) RA (n = 60) p -value Ultrasound findings Intima-media thickness R (mm) 0.65 ± 0.15 0.66 ± 0.14 0.346 b Intima-media thickness L (mm) 0.65 ± 0.15 0.68 ± 0.19 0.474 b Plaque D Yes 8 (13.3%) 6 (10%) 0.777 a No 52 (86.7%) 54 (90%) Plaque L Yes 4 (6.7%) 8 (13.3%) 0.362 a No 56 (93.3%) 52 (86.7%) Teicholz ejection fraction 65.92 ± 5.55 64.34 ± 5.35 0.097 b Diastolic dysfunction Yes 14 (23.3%) 8 (13.3%) 0.239 a No 46 (76.7%) 52 (86.7%) Data expressed as means ± standard deviation of the mean, or absolute numbers (n) and percentages (%). mm = millímeters. a Pearson’s chi-squared test. b Mann-Whitney test. Within the RA group, the DAS28-PCR scores were statistically similar for remission/low activity and moderate/high activity, left and right-side CIMT, and atherosclerosis plaque (Table 2 ), but diastolic dysfunction was more prevalent in patients with moderate/high activity (33.3%) than in patients with remission/low activity (5.7%) ( p = 0.044). Table 2 DAS28-PCR scores versus US findings in subjects with rheumatoid arthritis (RA) (n = 60). Variables DAS28-PCR p -value Remission/Low Moderate/High Echocardiographic findings Intima-media thickness R (mm) 0.66 ± 0.14 0.67 ± 0.15 0.837 b Intima-media thickness L (mm) 0.63 ± 0.11 0.75 ± 0.25 0.058 b Plaque R (n/%) Yes 4 (10.8) 2 (8.7) 1.000 a No 33 (89.2) 21 (91.3) Plaque L (n/%) Yes 5 (13.5) 3 (13.0) 1.000 a No 32 (86.5) 20 (87.0) Teicholz ejection fraction 63.33 ± 4.56 65.96 ± 6.18 Diastolic dysfunction (n/%) Yes 2 (5.7) 8 (33.3) 0.044 a No 35 (94.3) 16 (66.7) Data expressed as means ± standard deviation of the mean, or absolute numbers (n) and percentages (%). mm = millímeters. a Pearson’s chi-squared test. b Mann-Whitney test. Bold type = significant at 5% ( p < 0.05). When comparing low and moderate CVR in RA patients expressed in SCORE/mSCORE, some echocardiographic parameters were significantly different (Table 3 ). Thus, left and right-side CIMT values were significantly higher for moderate risk (0.69 mm and 0.71 mm; p = 0.048) than for low risk (0.62 mm and 0.60 mm; p < 0.001). Atherosclerosis plaque in the right carotid artery was also more common for moderate risk (14.5%) than for low risk (3.4%) ( p = 0.049). Finally, diastolic dysfunction was significantly more frequent among participants with moderate risk (32.1% vs. 5.2%; p < 0.001). Table 3 Association between echocardiographic findings and cardiovascular risk expressed in SCORE/mSCORE in subjects with rheumatoid arthritis (RA) (n = 60). Variables SCORE/mSCORE scores p -value Low Moderate Echocardiographic findings Intima-media thickness R (mm) 0.62 ± 0.12 0.69 ± 0.16 0.048 b Intima-media thickness L (mm) 0.60 ± 0.11 0.71 ± 0.18 < 0.001 b Plaque R (n/%) Yes 2 (3.4) 8 (14.5) 0.049 b No 56 (96.6) 47 (85.5) Plaque L (n/%) 0.089 a Yes 2 (3.4) 7 (12.7) No 56 (96.6) 48 (87.3) Teicholz ejection fraction Diastolic dysfunction (n/%) 64.92 ± 5.77 64.92 ± 5.77 0.538 b Yes 3 (5.2) 17 (32.1) < 0.001 b No 55 (94.8) 36 (67.9) Data expressed as means ± standard deviation of the mean, or absolute numbers (n) and percentages (%). mm = millímeters. a Pearson’s chi-squared test. b Mann-Whitney test. Bold type = significant at 5% ( p < 0.05). The Framingham scores assigned to the echocardiographic findings of the RA patients (Table 4 ) reflected major differences in mean CIMT, which was significantly greater for moderate/high risk on the right side (0.70 mm) and the left side (moderate 0.91 mm; high 0.74 mm) than for low risk (both 0.65 mm) ( p = 0.042 and p < 0.011, respectively). Atherosclerosis plaque in the carotids was also significantly more frequent in high-risk patients. Despite these structural changes, the ejection fraction and the prevalence of diastolic dysfunction were similar in the two groups ( p > 0.5). Table 4 Association between echocardiographic findings and cardiovascular risk expressed in Framingham scores in subjects with rheumatoid arthritis (RA) (n = 60). Variables Framingham scores p -value Low Moderate High Echocardiographic findings Intima-media thickness R (mm) 0.65 ± 0.15 0.7 ± 0.1 0.7 ± 0.03 0.042 b Intima-media thickness L (mm) 0.65 ± 0.17 0.91 ± 0.26 0.74 ± 0.19 < 0.011 b Plaque L (n/%) Yes 2 (3.9) 2 (40.0) 2 (50.0) 0.009 b No 49 (96.1) 3 (60.0) 2 (50.0) Plaque L (n/%) 0.020 a Yes 5 (9.8) 3 (60.0) 0 (0.0) No 46 (90.2) 2 (40.0) 4 (100.0) Teicholz ejection fraction Diastolic dysfunction (n/%) 64.22 ± 5.57 65.8 ± 2.28 64 ± 5.89 0.505 b Yes 7 (14.0) 0 (0.0) 1 (25.0) < 0.867 b No 43 (86.0) 4 (100.0) 3 (75.0) Data expressed as means ± standard deviation of the mean, or absolute numbers (n) and percentages (%). mm = millímeters. a Pearson’s chi-squared test. b Mann-Whitney test. Bold type = significant at 5% ( p < 0.05). No significant association was observed between the echocardiograhic parameters and disease duration (Table 5 ), nor between US changes and positivity for RF and/or anti-CCP (Table 6 ). Table 5 Association between echocardiographic findings and disease duration in subjects with rheumatoid arthritis (RA) (n = 60). Variables Disease duration p -value 1–5 years 5–10 years > 10 anos Echocardiographic findings Intima-media thickness R (mm) 0.63 ± 0.12 0.70 ± 0.11 0.67 ± 0.16 0.263 b Intima-media thickness L (mm) 0.64 ± 0.11 0.67 ± 0.11 0.70 ± 0.24 0.569 b Plaque R (n/%) Yes 1 (5.6) 1 (9.1) 4 (12.9) 0.849 b No 17 (94.4) 10 (90.9) 27 (87.1) Plaque L (n/%) Yes 1 (5.6) 2 (18.2) 5 (16.1) 0.596 a No 17 (94.4) 9 (81.8) 26 (83.9) Teicholz ejection fraction Diastolic dysfunction (n/%) 64.18 ± 4.98 63.64 ± 6.67 64.68 ± 5.21 0.733 b Yes 2 (11.1) 4 (36.4) 4 (12.9) 0.352 a No 16 (88.9) 7 (63.6) 27 (87.1) Data expressed as means ± standard deviation of the mean, or absolute numbers (n) and percentages (%). mm = millímeters. a Pearson’s chi-squared test. b Kruskal-Wallis test followed by Dunn’s post test. Table 6 Association between serum profile (rheumatoid factor and anti-CCP) and echocardiographic findings in subjects with rheumatoid arthritis (RA) (n = 60). Variables RF+ & anti-CCP+ RF + or anti-CCP+ RF- & anti-CCP- p -value Echocardiographic findings Intima-media thickness R (mm) 0.70 ± 0.16 0.63 ± 0.11 0.64 ± 0.14 0.307 b Intima-media thickness L (mm) 0.68 ± 0.18 0.62 ± 0.11 0.71 ± 0.22 0.537 b Plaque R (n/%) Yes 2 (7.7) 1 (8.3) 3 (13.6) 0.856 b No 24 (92.3) 11 (91.7) 19 (86.4) Plaque L (n/%) Yes 3 (11.5) 2 (16.7) 3 (13.6) 1.000 b No 23 (88.5) 10 (83.3) 19 (86.4) Teicholz ejection fraction 65.05 ± 5.38 63.58 ± 6.01 63.91 ± 5.09 0.660 b Diastolic dysfunction (n/%) Sim 5 (19.2) 1 (8.3) 3 (14.3) 0.895 a Não 21( 80.3) 11 (91.7) 18 (85.7) Data expressed as means ± standard deviation of the mean, or absolute numbers (n) and percentages (%). mm = millímeters. a Pearson’s chi-squared test. b Kruskal-Wallis test followed by Dunn’s post test. Discussion In this study we investigated cardiac and carotid functional and structural changes in RA patients and their association with disease activity, clinical findings and cardiovascular risk. The clinical SCORE/mSCORE and Framingham scores were statistically similar for RA patients and controls, but RA patients with high scores displayed changes on US, such as increased CIMT and prevalence of carotid atherosclerosis, suggesting subclinical vascular impairment. Despite the absence of statistical significance between RA patients and controls with regard to overall cardiac and carotid US parameters, when we stratified the data, the results proved to be relevant. Thus, the fact that diastolic dysfunction was significantly more frequent in RA patients with moderate/high disease activity suggests an association between systemic inflammation and functional cardiac impairment. Moreover, subjects with moderate CVR also tended to have more severe arterial thickening, carotid plaque and diastolic dysfunction. These findings are consistent with published evidence that 30% of cardiovascular risk in RA patients is due to the disease, while the remaining 70% is explained by traditional CVRFs like hypertension and smoking [ 30 ]. In our RA patients, the highest risk scores coincided with US changes suggestive of subclinical atherosclerosis. Clinical CVR scores like Framingham and SCORE are widely used in clinical practice to estimate the 10-year risk of cardiovascular events, but evidence shows that these models are of limited usefulness in patients with autoimmune disease, such as RA, because they do not adequately take into account the role of chronic inflammation in the development of atherosclerosis [ 31 ]. Even the correction factor of 1.5 proposed by EULAR seems insufficient to assess the actual risk in this patient population [ 32 ]. On the other hand, the evaluation of subclinical atherosclerosis on carotid US―a non-invasive, low-cost, reproducible and sensitive method capable of early detection of structural changes, such as increased CIMT and plaque formation―has been shown to compensate for this shortcoming. In short, combining clinical scores and US findings allows for a more accurate and low-cost risk stratification of RA patients, hence earlier and more targeted interventions [ 33 ]. The prevalence of diastolic dysfunction in RA patients is reported to be between 31% and > 50%, depending on population profile and follow-up time. The change is usually detected on Doppler echocardiography, even in patients with preserved ejection fraction and without evident cardiovascular symptoms [ 34 – 38 ]. Disease activity, as expressed by increased DAS28 and CDAI scores and levels of CRP and ESR, is independently correlated with the presence and severity of diastolic dysfunction [ 34 – 41 ]. Patients with active RA are known to be at a significantly higher risk of heart failure, especially diastolic, than patients with RA in remission or low activity [ 39 , 40 ]. The fact that the prevalence of diastolic dysfunction was similar in healthy controls and in RA patients with low disease activity suggests that careful control of inflammation can mitigate subclinical CVR [ 41 ]. The finding in the present study of an association between diastolic dysfunction and high RA activity supports this notion. The correlation in RA patients between high clinical CVR scores and US findings suggestive of subclinical atherosclerosis has been pointed out elsewhere, but the literature on this specific topic is very limited [ 42 ]. Importantly, the association established in our study between cardiovascular changes (diastolic dysfunction, increased CIMT, atherosclerosis plaque) and high clinical CVR scores highlights the need for an integrated approach to CVR in this patient population, combining clinical stratification, US scanning, and monitoring of inflammatory activity [ 15 – 17 ]. No association was found between disease duration and cardiovascular changes. Classically, disease duration has been regarded as an independent predictor of arterial stiffness, since aging of the arteries is more accelerated in RA than in healthy controls [ 43 ], and since the cumulative damage caused by RA is greater in patients with ≥ 10 years of disease, even in the absence of traditional CVRFs [ 44 ]. Interestingly, neither did we observe any association between positivity for antibodies and changes on US. Cohort studies with long follow-up have shown that both RF and anti-CCP are associated with an increased incidence of cardiovascular events in patients with established RA, including acute coronary syndrome, stroke, and cardiovascular death [ 45 , 46 ]. The risk is particularly high in subjects with high anti-CCP titers. On the other hand, and supporting our findings, a large cohort study concluded that, if traditional CVRFs and systemic inflammation are adjusted for, positivity for RF or anti-CCP is in itself not a robust, independent predictor of cardiovascular events, with inflammatory activity and disease severity being the main risk determinants [ 47 ]. Considering that systemic inflammation is a major factor in the acceleration of atherosclerosis in RA, the absence in our study of a significant association between disease duration, serum positivity and structural and functional cardiovascular changes may in part be explained by the fact that over 60% of our sample displayed RA in remission/low activity due to efficient clinical control. The strengths of this study include i) our integrated approach (combining echocardiography and carotid US) to improve the analysis of structural and functional cardiovascular changes and subclinical atherosclerosis, and ii) the combination of US findings with CVR scores to improve the correlation between these parameters and cardiac screening in RA. On the other hand, the study was limited by i) the small sample size, ii) the single-center design, iii) the cross-sectional observational design, and iv) the lack of multivariate analysis to identify independent predictors of CVR in RA patients submitted to US. Conclusion In conclusion, our findings show that inflammatory activity played a major role in subclinical cardiovascular dysfunction in a sample of RA patients. Hence, US screening of the heart and carotids should be considered for earlier detection and intervention, especiallly in subjects with active RA or additional CVRFs. Furter investigations are needed to explore the methods of early detection of CVRFs in RA. Declarations Acknowledgments We would like to thank Fundação Edson Queiroz for logistical support and assistance. Availability of data and materials The data that support the finding of this study are available on a reasonable request from the corresponding author. Conflict of interest None to declare . Funding The authors received financial support from the SUS Research Program ‘Shared Management in Health’/PPSUS-CE-FUNCAP-SESA-Decit/SCTIE/MS-CNPq (02/2020). The investigators Paula Goes, Hellíada Vasconcelos Chaves and Mirna Marques Bezerra are affiliated with CNPq (National Council for Scientific and Technological Development). The investigator Vicente de Paulo Teixeira Pinto is affiliated with FUNCAP (Ceará Foundation for Scientific and Technological Development). Authors' contributions Christiane Aguiar Nobre: Writing – review & editing, Writing – original draft, Data curation, Validation, Resources, Project administration, Methodology, Investigation, Formal analysis. Carlos Ewerton Maia Rodrigues: Writing – review & editing, Writing- original draft, Formal analysis, Data curation, Conceptualization, Methodology. Investigation, Formal analysis. Luzia Keyne Sousa Carneiro Frota: Data curation. Natacha Xavier Cavalcante : Writing – review & editing. Thácilla Siqueira Eugênio Nascimento: Methodology . João Gabriel Marques Brayner: Writing – review & editing. Giovanna Azevedo Sousa: Data curation. Paula Goes: Writing – review & editing, Writing – original draft. Vicente de Paulo Teixeira Pinto: Methodology, Data curation. Hellíada Vasconcelos Chaves: Writing – review & editing. Mirna Marques Bezerra: Writing – review & editing, Writing – original draft, Data curation, Conceptualization, Validation, Resources, Project administration, Methodology, Investigation, Formal analysis. References Pujades-Rodriguez M, George J, van Staa TP, Stogiannis D, Rahman A, Smeeth L et al (2016) Rheumatoid arthritis and incidence of twelve initial presentations of cardiovascular disease: a population record-linkage cohort study in England. 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Front Med (Lausanne) 9:786776. https://doi:10.3389/fmed.2022.786776 Moreno RA, Ayala Ugarte C, Hernández EA, Sánchez Olivan E, Leal Villanueva DI, Flores Serrano F et al (2025) Unmasking subclinical atherosclerosis: the impact of carotid ultrasound on the evaluation of patients with rheumatoid arthritis. Cureus 17:e80525. https://doi:10.7759/cureus.80525 Park E, Ito K, Iqbal R, Zins M, Goldberg M, Morelle G et al (2022) Rheumatoid arthritis, as a clinical disease, but not rheumatoid arthritis-associated autoimmunity, is linked to cardiovascular events. Arthritis Res Ther 24:184. https://doi:10.1186/s13075-022-02864-0 Kim GH, Park YJ (2021) Low levels of PCSK9 are associated with remission in patients with rheumatoid arthritis treated with anti-TNF-α: potential underlying mechanisms. Arthritis Res Ther 23:247. https://doi:10.1186/s13075-021-02629-1 Maiello M, Cecere A, Ciccone MM, Palmiero P (2023) Cardiac remodeling in rheumatoid arthritis: a focus on the left atrium. Clin Physiol Funct Imaging 43(5):313–317. 10.1111/cpf.12822 Liang KP, Myasoedova E, Crowson CS, Davis JM, Roger VL, Karon BL et al (2010) Increased prevalence of diastolic dysfunction in rheumatoid arthritis. Ann Rheum Dis 69:1665–1670. https://doi:10.1136/ard.2009.124362 Aslam F, Bandeali SJ, Khan NA, Alam M (2013) Diastolic dysfunction in rheumatoid arthritis: a meta-analysis and systematic review. Arthritis Care Res (Hoboken) 65:534–543. https://doi:10.1002/acr.21861 Schau T, Gottwald M, Arbach O, Seifert M, Schöpp M, Neuß M et al (2015) Increased prevalence of diastolic heart failure in patients with rheumatoid arthritis correlates with active disease, but not with treatment type. J Rheumatol 42:2029–2037. https://doi:10.3899/jrheum.141647 Biskup M, Biskup W, Majdan M, Targońska-Stępniak B (2018) Cardiovascular system changes in rheumatoid arthritis patients with continued low disease activity. Rheumatol Int 38:1207–1215. https://doi:10.1007/s00296-018-4053-x Targońska-Stępniak B, Biskup M, Biskup W, Majdan M (2019) Diastolic dysfunction in rheumatoid arthritis patients with low disease activity. Clin Rheumatol 38:1131–1137. https://doi:10.1007/s10067-018-4369-7 Hughes DM, Coronado JIC, Schofield P, Yiu ZZN, Zhao SS (2024) The predictive accuracy of cardiovascular disease risk prediction tools in inflammatory arthritis and psoriasis: an observational validation study using the Clinical Practice Research Datalink. Rheumatology (Oxford) 63:3432–3441. https://doi:10.1093/rheumatology/kead610 Mong N, Tarjanyi Z, Tothfalusi L, Bartykowszki A, Nagy AI, Szekely A et al (2020) Largely accelerated arterial aging in rheumatoid arthritis is associated with inflammatory activity and smoking in the early stage of the disease. Front Pharmacol 11:523962. https://doi:10.3389/fphar.2020.601344 Vázquez-Del Mercado M, Gomez-Bañuelos E, Chavarria-Avila E, Cardona-Muñoz E, Ramos-Becerra C, Alanis-Sanchez A et al (2017) Disease duration of rheumatoid arthritis is a predictor of vascular stiffness: a cross-sectional study in patients without known cardiovascular comorbidities: a STROBE-compliant article. Med (Baltim) 96:e7862. https://doi:10.1097/MD.0000000000007862 Westerlind H, Rönnelid J, Hansson M, Alfredsson L, Mathsson-Alm L, Serre G et al (2020) Anti-citrullinated protein antibody specificities, rheumatoid factor isotypes, and incident cardiovascular events in patients with rheumatoid arthritis. Arthritis Rheumatol 72:1658–1667. https://doi:10.1002/art.41381 Berendsen MLT, van Maaren MC, Arts EEA, den Broeder AA, Popa CD, Fransen J (2017) Anticyclic citrullinated peptide antibodies and rheumatoid factor as risk factors for 10-year cardiovascular morbidity in patients with rheumatoid arthritis: a large inception cohort study. J Rheumatol 44:1325–1330. https://doi:10.3899/jrheum.160670 Mackey RH, Kuller LH, Deane KD, Walitt BT, Chang YF, Holers VM et al (2015) Rheumatoid arthritis, anti-cyclic citrullinated peptide positivity, and cardiovascular disease risk in the Women's Health Initiative. Arthritis Rheumatol 67:2311–2322. https://doi:10.1002/art.39198 Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 02 Jan, 2026 Reviewers invited by journal 02 Dec, 2025 Editor assigned by journal 16 Nov, 2025 First submitted to journal 15 Nov, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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rheumatoid arthritis (RA) is considered an independent cardiovascular risk factor (CVRF) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. As shown in the literature, RA patients are at a significantly higher risk of cardiovascular events and mortality than the general population [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], mostly due to persistent systemic inflammation.\u003c/p\u003e\u003cp\u003eDisease activity in patients with RA is directly related to cardiovascular risk, and this risk is proportional to the intensity and persistence of systemic inflammation, which contributes to endothelial dysfunction, lipid alterations, and a higher prevalence of subclinical atherosclerotic plaques [\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe repercussion of RA on the cardiovascular system are multifaceted and generally involve structural and functional changes to the heart[\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Functional changes often include diastolic dysfunction and reduced ejection fraction [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAn understanding of the negative impact of cardiovascular disease (CVD) on overall health, quality of life and life expectancy, as well as of the early detection of subclinical signs, is essential for risk stratification and management of RA patients. Ultrasonography (US) is usually employed to this end, but the ideal method has not yet been established [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. US modalities like transthoracic echocardiography and Doppler carotid ecography are low-cost, non-invasive and sensitive tools in cardiovascular screening [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. In fact, a study on 104 RA patients found carotid US to be more sensitive than coronary artery calcium scores in the detection of subclinical atherosclerosis in RA [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe combination of traditional clinical scores with cardiac and carotid imaging methods is recommended to enhance cardiovascular risk assessment. The populations that benefit most from integrating traditional clinical scores with cardiac and carotid imaging methods for cardiovascular risk assessment are asymptomatic adults classified as low to intermediate risk by traditional scores (such as Framingham, SCORE), particularly those aged 40 to 65 years, without known cardiovascular disease[\u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn view of the known association disease activity in patients with RA and increased CVRF, the clinical benefit of early risk stratification, this study we evaluated the association between disease activity and subclinical diastolic dysfunction in RA in Northeastern Brazil.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003ePatients\u003c/h2\u003e\u003cp\u003e This cross-sectional study was conducted at a secondary-level health care facility in Northeastern Brazil between October 2021 and October 2022. The study protocol complied with the principles of the Declaration of Helsinkki [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] and was approved under #10729/2020 by the research ethics committee of the Federal University of Cear\u0026aacute; (CEP/UFC/PROPESQ). All procedures followed well-established research standards and guidelines, and all participants gave their informed written consent prior to entering the study.\u003c/p\u003e\u003cp\u003eThe sample consisted of 120 participants, of which half were RA patients and half were sex and age-matched healthy controls recruited from the local community. All RA patients met the 2010 diagnostic criteria of the American College of Rheumatology[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. The exclusion criteria were age under 18 years, pregnancy, previously diagnosed CVD, chronic kidney failure, and association with collagen disorders such as systemic lupus erythematosus, Sj\u0026ouml;gren syndrome, inflammatory myopathy, and sclerodermia.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eSample size calculation\u003c/h3\u003e\n\u003cp\u003eThe sample size was calculated considering carotid intima-media thickness (CIMT) as primary variable outcome. In an earlier study [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], patients with recent-onset RA had an average CIMT of 0.64\u0026thinsp;\u0026plusmn;\u0026thinsp;0.13 mm, compared to 0.58\u0026thinsp;\u0026plusmn;\u0026thinsp;0.09 mm in healthy controls. Based on this expected difference, we estimated that a statistical power of 80% at the 5% level of significance (α\u0026thinsp;=\u0026thinsp;0.05) would require at least 55 participants per group. In this study, each group included 60 subjects, matching the design adopted in another cross-sectional study [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003eClinical and anthropometric evaluation\u003c/h3\u003e\n\u003cp\u003eThe collected information included epidemiological, clinical and laboratory data, such as blood count, C-reactive protein, rheumatoid factor (RF), anti-cyclic citrullinated peptide antibody (anti-CCP), glycemia, total cholesterol, high-density lipoprotein (HDL-c), low-density lipoprotein (LDL-c), and triglycerides.\u003c/p\u003e\u003cp\u003eThe 10-year cardiovascular risk was assessed using the systematic coronary risk evaluation (SCORE), the modified SCORE (mSCORE), and the Framingham score [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. To calculate mSCORE, we multiplied the SCORE index by 1.5 in RA patients meeting at least 2 of the following 3 criteria: disease duration\u0026thinsp;\u0026gt;\u0026thinsp;10 years, positivity for FR and/or anti-CCP, and extra-articular manifestations [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eUpon physical examination, information was collected on the number of painful and swollen joints, arterial blood pressure, waist circumference (WC), and body-mass index (BMI). WC was measured with a tape positioned horizontally between the iliac crest and the lowest rib. BMI was calculated by dividing the weight by the height squared (kg/m\u0026sup2;). Overweight was defined as BMI 25.0-29.9 kg/m\u0026sup2; and obesity was defined as \u0026ge;\u0026thinsp;30.0 kg/m\u0026sup2;.\u003c/p\u003e\u003cp\u003eDisease activity was scored with the composite index DAS28-CRP, using the following interpretation: \u0026lt;2.6\u0026thinsp;=\u0026thinsp;clinical remission; 2.6\u0026ndash;3.1\u0026thinsp;=\u0026thinsp;low activity; 3.2-5.0\u0026thinsp;=\u0026thinsp;moderate activity; \u0026gt;5.1\u0026thinsp;=\u0026thinsp;high activity [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003eUltrasound evaluation\u003c/h3\u003e\n\u003cp\u003eBoth groups of participants were submitted to cardiac and carotid US by a cardiologist (LKSCF) trained and experienced in the respective US techniques. Carotid US in B-mode with spectral Doppler allowed to conduct a morphological and hemodynamic analysis, with emphasis on CIMT measurement and the detection of atherosclerosis plaque―a well established marker of subclinical atherosclerosis [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Cardiac function was evaluated by 2-dimensional transthoracic echocardiography while the left ventricle ejection fraction (LVEF) was determined with the Teicholz method, following the guidelines of the American Society of Echocardiography [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e].\u003c/p\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eClinical and demographic variables, when quantitative and continuous, were expressed as means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) and medians\u0026thinsp;+\u0026thinsp;interquartile range, or, when categorical, as absolute numbers (n) and percentages (%). The main groups (RA vs. controls) and the CVRF subgroups were compared with the chi-squared test (categorical variables) or the Mann-Whitney and Kruskal-Wallis test (non-parametric and continuous variables). All statistical analyses were performed with the software SPSS v. 26.0 (IBM Corp., Armonk, NY, USA) at the 5% level of significance (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe female sex was predominant in both the RA group (91.7%) and the control group (90%). The mean age was 52\u0026thinsp;\u0026plusmn;\u0026thinsp;12 years and 52\u0026thinsp;\u0026plusmn;\u0026thinsp;13 years, respectively.\u003c/p\u003e\u003cp\u003eIn the case-control analysis, when comparing the groups with regard to traditional CVRFs (family history of CVD, current or previous smoking, arterial hypertension, diabetes mellitus, sedentary lifestyle, systolic and diastolic blood pressure, total cholesterol, HDL and LDL), no significant difference was observed (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Likewise, the two groups were statistically similar with regard to IMC and the distribution of low weight, overweight and obesity, but the prevalence of dyslipidemia was significantly higher in the control group (55.0%) than in the RA group (33.3%) (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.027). Moreover, the controls displayed higher WC (91.67 cm vs. 87.65 cm; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.017) and BMI values (28.58 vs. 26.83; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.010). As for laboratory parameters, the controls had significantly higher levels of glycemia (109.95 mg/dL vs. 93.92 mg/dL; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and triglycerides (154.27 mg/dL vs. 114.37 mg/dL; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004).\u003c/p\u003e\u003cp\u003eThe mean disease duration was 10.43\u0026thinsp;\u0026plusmn;\u0026thinsp;7.55 years, distributed as follows: 1\u0026ndash;5 years\u0026thinsp;=\u0026thinsp;30%, 5\u0026ndash;10 years\u0026thinsp;=\u0026thinsp;18.3%, and \u0026gt;\u0026thinsp;10 years\u0026thinsp;=\u0026thinsp;51.7%. The mean time since diagnosis was 8.57\u0026thinsp;\u0026plusmn;\u0026thinsp;6.84 years. Positivity for either RF or anti-CCP was 20%, for both 43.3%, and for neither 36.7%. According to the DAS-28 PCR scoring system, 61.7% were classified as remission or low activity. The remainder (31.3%) had moderate or high activity.\u003c/p\u003e\u003cp\u003eWith regard to therapy, 59 of the 60 patients (98.3%) were treated with disease-modifying antirheumatic drugs (DMARDs), primarily csDMARDs (n\u0026thinsp;=\u0026thinsp;55; 91.7%) used alone (n\u0026thinsp;=\u0026thinsp;39; 66.1%) or in combination with biological DMARDs (n\u0026thinsp;=\u0026thinsp;13; 22.0%) or targeted DMARDs (n\u0026thinsp;=\u0026thinsp;7; 11.9%). Current use of corticosteroids was reported by 26.7%, while methotrexate was used by 72.9%.\u003c/p\u003e\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the CVRFs of participants with and without RA expressed in SCORE/mSCORE and Framingham scores. According to the SCORE/mSCORE index, low risk was assigned to 45% of the RA patients and to 55.4% of the controls. Moderate risk was higher among RA patients (55% vs. 44.6%), but the difference was not significant (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.261). The mean Framingham score was slightly higher in the control group (8.34\u0026thinsp;\u0026plusmn;\u0026thinsp;8.95%) than in the RA group (6.33\u0026thinsp;\u0026plusmn;\u0026thinsp;6.78%), though not significantly (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.208). When arranged by category, low CVR (\u0026le;\u0026thinsp;10%) was assigned to 68.3% of the controls and to 85% of the RA patients. Moderate risk (10\u0026ndash;20%) and high risk (\u0026ge;\u0026thinsp;20%) were less frequent in the RA group, though not significantly.\u003c/p\u003e\u003cp\u003eCardiac and carotid US findings were statistically similar in the two groups with regard to CVR parameters (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eCardiovascular risk factors (CVRFs) determined by ultrasound scanning of subjects without (controls) and with rheumatoid arthritis (RA).\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eControls (n\u0026thinsp;=\u0026thinsp;60)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRA (n\u0026thinsp;=\u0026thinsp;60)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUltrasound findings\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIntima-media thickness R (mm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.65\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.66\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.346 \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIntima-media thickness L (mm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.65\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.68\u0026thinsp;\u0026plusmn;\u0026thinsp;0.19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.474 \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlaque D\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (13.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (10%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.777 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e52 (86.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e54 (90%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlaque L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (6.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (13.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.362 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e56 (93.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e52 (86.7%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTeicholz ejection fraction\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e65.92\u0026thinsp;\u0026plusmn;\u0026thinsp;5.55\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e64.34\u0026thinsp;\u0026plusmn;\u0026thinsp;5.35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.097 \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiastolic dysfunction\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14 (23.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (13.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.239 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e46 (76.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e52 (86.7%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eData expressed as means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation of the mean, or absolute numbers (n) and percentages (%). mm\u0026thinsp;=\u0026thinsp;mill\u0026iacute;meters. \u003csup\u003ea\u003c/sup\u003e Pearson\u0026rsquo;s chi-squared test. \u003csup\u003eb\u003c/sup\u003e Mann-Whitney test.\u003c/p\u003e\u003cp\u003eWithin the RA group, the DAS28-PCR scores were statistically similar for remission/low activity and moderate/high activity, left and right-side CIMT, and atherosclerosis plaque (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), but diastolic dysfunction was more prevalent in patients with moderate/high activity (33.3%) than in patients with remission/low activity (5.7%) (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.044).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDAS28-PCR scores \u003cem\u003eversus\u003c/em\u003e US findings in subjects with rheumatoid arthritis (RA) (n\u0026thinsp;=\u0026thinsp;60).\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eVariables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eDAS28-PCR\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRemission/Low\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eModerate/High\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEchocardiographic findings\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIntima-media thickness R (mm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.66\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.837\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIntima-media thickness L (mm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.63\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.75\u0026thinsp;\u0026plusmn;\u0026thinsp;0.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.058\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlaque R (n/%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 (10.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (8.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e1.000\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e33 (89.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21 (91.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlaque L (n/%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (13.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (13.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e1.000\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e32 (86.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20 (87.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTeicholz ejection fraction\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e63.33\u0026thinsp;\u0026plusmn;\u0026thinsp;4.56\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e65.96\u0026thinsp;\u0026plusmn;\u0026thinsp;6.18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiastolic dysfunction (n/%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (5.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (33.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003e0.044\u003c/b\u003e\u003csup\u003e\u003cb\u003ea\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e35 (94.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16 (66.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eData expressed as means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation of the mean, or absolute numbers (n) and percentages (%). mm\u0026thinsp;=\u0026thinsp;mill\u0026iacute;meters. \u003csup\u003ea\u003c/sup\u003e Pearson\u0026rsquo;s chi-squared test. \u003csup\u003eb\u003c/sup\u003e Mann-Whitney test. Bold type\u0026thinsp;=\u0026thinsp;significant at 5% (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003cp\u003eWhen comparing low and moderate CVR in RA patients expressed in SCORE/mSCORE, some echocardiographic parameters were significantly different (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Thus, left and right-side CIMT values were significantly higher for moderate risk (0.69 mm and 0.71 mm; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.048) than for low risk (0.62 mm and 0.60 mm; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Atherosclerosis plaque in the right carotid artery was also more common for moderate risk (14.5%) than for low risk (3.4%) (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.049). Finally, diastolic dysfunction was significantly more frequent among participants with moderate risk (32.1% vs. 5.2%; \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eAssociation between echocardiographic findings and cardiovascular risk expressed in SCORE/mSCORE in subjects with rheumatoid arthritis (RA) (n\u0026thinsp;=\u0026thinsp;60).\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eVariables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eSCORE/mSCORE scores\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLow\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eModerate\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEchocardiographic findings\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIntima-media thickness R (mm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.62\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.69\u0026thinsp;\u0026plusmn;\u0026thinsp;0.16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.048\u003c/b\u003e\u003csup\u003e\u003cb\u003eb\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIntima-media thickness L (mm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.60\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.71\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003csup\u003e\u003cb\u003eb\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlaque R (n/%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (3.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (14.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.049\u003c/b\u003e\u003csup\u003e\u003cb\u003eb\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e56 (96.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e47 (85.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlaque L (n/%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.089\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (3.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (12.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e56 (96.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e48 (87.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTeicholz ejection fraction\u003c/p\u003e\u003cp\u003eDiastolic dysfunction (n/%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e64.92\u0026thinsp;\u0026plusmn;\u0026thinsp;5.77\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e64.92\u0026thinsp;\u0026plusmn;\u0026thinsp;5.77\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.538\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (5.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e17 (32.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.001\u003c/b\u003e\u003csup\u003e\u003cb\u003eb\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e55 (94.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e36 (67.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eData expressed as means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation of the mean, or absolute numbers (n) and percentages (%). mm\u0026thinsp;=\u0026thinsp;mill\u0026iacute;meters. \u003csup\u003ea\u003c/sup\u003e Pearson\u0026rsquo;s chi-squared test. \u003csup\u003eb\u003c/sup\u003e Mann-Whitney test. Bold type\u0026thinsp;=\u0026thinsp;significant at 5% (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003cp\u003eThe Framingham scores assigned to the echocardiographic findings of the RA patients (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e) reflected major differences in mean CIMT, which was significantly greater for moderate/high risk on the right side (0.70 mm) and the left side (moderate 0.91 mm; high 0.74 mm) than for low risk (both 0.65 mm) (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.042 and \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.011, respectively). Atherosclerosis plaque in the carotids was also significantly more frequent in high-risk patients. Despite these structural changes, the ejection fraction and the prevalence of diastolic dysfunction were similar in the two groups (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.5).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eAssociation between echocardiographic findings and cardiovascular risk expressed in Framingham scores in subjects with rheumatoid arthritis (RA) (n\u0026thinsp;=\u0026thinsp;60).\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eVariables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eFramingham scores\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLow\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eModerate\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eHigh\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEchocardiographic findings\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIntima-media thickness R (mm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.65\u0026thinsp;\u0026plusmn;\u0026thinsp;0.15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.042\u003c/b\u003e\u003csup\u003e\u003cb\u003eb\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIntima-media thickness L (mm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.65\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.91\u0026thinsp;\u0026plusmn;\u0026thinsp;0.26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.74\u0026thinsp;\u0026plusmn;\u0026thinsp;0.19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.011\u003c/b\u003e\u003csup\u003e\u003cb\u003eb\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlaque L (n/%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (3.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (40.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (50.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.009\u003c/b\u003e\u003csup\u003e\u003cb\u003eb\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e49 (96.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (60.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (50.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlaque L (n/%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.020\u003c/b\u003e\u003csup\u003e\u003cb\u003ea\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (9.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (60.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e46 (90.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (40.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4 (100.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTeicholz ejection fraction\u003c/p\u003e\u003cp\u003eDiastolic dysfunction (n/%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e64.22\u0026thinsp;\u0026plusmn;\u0026thinsp;5.57\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e65.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e64\u0026thinsp;\u0026plusmn;\u0026thinsp;5.89\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.505\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (14.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0 (0.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (25.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.867\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e43 (86.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (100.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (75.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eData expressed as means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation of the mean, or absolute numbers (n) and percentages (%). mm\u0026thinsp;=\u0026thinsp;mill\u0026iacute;meters. \u003csup\u003ea\u003c/sup\u003e Pearson\u0026rsquo;s chi-squared test. \u003csup\u003eb\u003c/sup\u003e Mann-Whitney test. Bold type\u0026thinsp;=\u0026thinsp;significant at 5% (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003cp\u003eNo significant association was observed between the echocardiograhic parameters and disease duration (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e), nor between US changes and positivity for RF and/or anti-CCP (Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eAssociation between echocardiographic findings and disease duration in subjects with rheumatoid arthritis (RA) (n\u0026thinsp;=\u0026thinsp;60).\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eVariables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003eDisease duration\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u0026ndash;5 years\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5\u0026ndash;10 years\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;10 anos\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEchocardiographic findings\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIntima-media thickness R (mm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.63\u0026thinsp;\u0026plusmn;\u0026thinsp;0.12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.70\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.263\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIntima-media thickness L (mm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.64\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.70\u0026thinsp;\u0026plusmn;\u0026thinsp;0.24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.569\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlaque R (n/%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (5.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (9.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4 (12.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.849\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17 (94.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10 (90.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e27 (87.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlaque L (n/%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (5.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (18.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5 (16.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.596\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e17 (94.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (81.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e26 (83.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTeicholz ejection fraction\u003c/p\u003e\u003cp\u003eDiastolic dysfunction (n/%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e64.18\u0026thinsp;\u0026plusmn;\u0026thinsp;4.98\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e63.64\u0026thinsp;\u0026plusmn;\u0026thinsp;6.67\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e64.68\u0026thinsp;\u0026plusmn;\u0026thinsp;5.21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.733\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (11.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (36.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4 (12.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.352\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16 (88.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (63.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e27 (87.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eData expressed as means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation of the mean, or absolute numbers (n) and percentages (%). mm\u0026thinsp;=\u0026thinsp;mill\u0026iacute;meters. \u003csup\u003ea\u003c/sup\u003e Pearson\u0026rsquo;s chi-squared test. \u003csup\u003eb\u003c/sup\u003e Kruskal-Wallis test followed by Dunn\u0026rsquo;s post test.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eAssociation between serum profile (rheumatoid factor and anti-CCP) and echocardiographic findings in subjects with rheumatoid arthritis (RA) (n\u0026thinsp;=\u0026thinsp;60).\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRF+ \u0026amp; anti-CCP+\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eRF\u0026thinsp;+\u0026thinsp;or anti-CCP+\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eRF- \u0026amp; anti-CCP-\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEchocardiographic findings\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIntima-media thickness R (mm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.70\u0026thinsp;\u0026plusmn;\u0026thinsp;0.16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.63\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.64\u0026thinsp;\u0026plusmn;\u0026thinsp;0.14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.307\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIntima-media thickness L (mm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.68\u0026thinsp;\u0026plusmn;\u0026thinsp;0.18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.62\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.71\u0026thinsp;\u0026plusmn;\u0026thinsp;0.22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.537\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlaque R (n/%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (7.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (8.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (13.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.856\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24 (92.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11 (91.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e19 (86.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlaque L (n/%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (11.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (16.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (13.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e1.000\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e23 (88.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10 (83.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e19 (86.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTeicholz ejection fraction\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e65.05\u0026thinsp;\u0026plusmn;\u0026thinsp;5.38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e63.58\u0026thinsp;\u0026plusmn;\u0026thinsp;6.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e63.91\u0026thinsp;\u0026plusmn;\u0026thinsp;5.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.660\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiastolic dysfunction (n/%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSim\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (19.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1 (8.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (14.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.895\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eN\u0026atilde;o\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21( 80.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11 (91.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e18 (85.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eData expressed as means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation of the mean, or absolute numbers (n) and percentages (%). mm\u0026thinsp;=\u0026thinsp;mill\u0026iacute;meters. \u003csup\u003ea\u003c/sup\u003e Pearson\u0026rsquo;s chi-squared test. \u003csup\u003eb\u003c/sup\u003e Kruskal-Wallis test followed by Dunn\u0026rsquo;s post test.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study we investigated cardiac and carotid functional and structural changes in RA patients and their association with disease activity, clinical findings and cardiovascular risk. The clinical SCORE/mSCORE and Framingham scores were statistically similar for RA patients and controls, but RA patients with high scores displayed changes on US, such as increased CIMT and prevalence of carotid atherosclerosis, suggesting subclinical vascular impairment.\u003c/p\u003e\u003cp\u003eDespite the absence of statistical significance between RA patients and controls with regard to overall cardiac and carotid US parameters, when we stratified the data, the results proved to be relevant. Thus, the fact that diastolic dysfunction was significantly more frequent in RA patients with moderate/high disease activity suggests an association between systemic inflammation and functional cardiac impairment. Moreover, subjects with moderate CVR also tended to have more severe arterial thickening, carotid plaque and diastolic dysfunction. These findings are consistent with published evidence that 30% of cardiovascular risk in RA patients is due to the disease, while the remaining 70% is explained by traditional CVRFs like hypertension and smoking [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn our RA patients, the highest risk scores coincided with US changes suggestive of subclinical atherosclerosis. Clinical CVR scores like Framingham and SCORE are widely used in clinical practice to estimate the 10-year risk of cardiovascular events, but evidence shows that these models are of limited usefulness in patients with autoimmune disease, such as RA, because they do not adequately take into account the role of chronic inflammation in the development of atherosclerosis [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Even the correction factor of 1.5 proposed by EULAR seems insufficient to assess the actual risk in this patient population [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. On the other hand, the evaluation of subclinical atherosclerosis on carotid US―a non-invasive, low-cost, reproducible and sensitive method capable of early detection of structural changes, such as increased CIMT and plaque formation―has been shown to compensate for this shortcoming. In short, combining clinical scores and US findings allows for a more accurate and low-cost risk stratification of RA patients, hence earlier and more targeted interventions [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe prevalence of diastolic dysfunction in RA patients is reported to be between 31% and \u0026gt;\u0026thinsp;50%, depending on population profile and follow-up time. The change is usually detected on Doppler echocardiography, even in patients with preserved ejection fraction and without evident cardiovascular symptoms [\u003cspan additionalcitationids=\"CR35 CR36 CR37\" citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. Disease activity, as expressed by increased DAS28 and CDAI scores and levels of CRP and ESR, is independently correlated with the presence and severity of diastolic dysfunction [\u003cspan additionalcitationids=\"CR35 CR36 CR37 CR38 CR39 CR40\" citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. Patients with active RA are known to be at a significantly higher risk of heart failure, especially diastolic, than patients with RA in remission or low activity [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. The fact that the prevalence of diastolic dysfunction was similar in healthy controls and in RA patients with low disease activity suggests that careful control of inflammation can mitigate subclinical CVR [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. The finding in the present study of an association between diastolic dysfunction and high RA activity supports this notion.\u003c/p\u003e\u003cp\u003eThe correlation in RA patients between high clinical CVR scores and US findings suggestive of subclinical atherosclerosis has been pointed out elsewhere, but the literature on this specific topic is very limited [\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. Importantly, the association established in our study between cardiovascular changes (diastolic dysfunction, increased CIMT, atherosclerosis plaque) and high clinical CVR scores highlights the need for an integrated approach to CVR in this patient population, combining clinical stratification, US scanning, and monitoring of inflammatory activity [\u003cspan additionalcitationids=\"CR16\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eNo association was found between disease duration and cardiovascular changes. Classically, disease duration has been regarded as an independent predictor of arterial stiffness, since aging of the arteries is more accelerated in RA than in healthy controls [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e], and since the cumulative damage caused by RA is greater in patients with \u0026ge;\u0026thinsp;10 years of disease, even in the absence of traditional CVRFs [\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. Interestingly, neither did we observe any association between positivity for antibodies and changes on US. Cohort studies with long follow-up have shown that both RF and anti-CCP are associated with an increased incidence of cardiovascular events in patients with established RA, including acute coronary syndrome, stroke, and cardiovascular death [\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e, \u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]. The risk is particularly high in subjects with high anti-CCP titers. On the other hand, and supporting our findings, a large cohort study concluded that, if traditional CVRFs and systemic inflammation are adjusted for, positivity for RF or anti-CCP is in itself not a robust, independent predictor of cardiovascular events, with inflammatory activity and disease severity being the main risk determinants [\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eConsidering that systemic inflammation is a major factor in the acceleration of atherosclerosis in RA, the absence in our study of a significant association between disease duration, serum positivity and structural and functional cardiovascular changes may in part be explained by the fact that over 60% of our sample displayed RA in remission/low activity due to efficient clinical control.\u003c/p\u003e\u003cp\u003eThe strengths of this study include i) our integrated approach (combining echocardiography and carotid US) to improve the analysis of structural and functional cardiovascular changes and subclinical atherosclerosis, and ii) the combination of US findings with CVR scores to improve the correlation between these parameters and cardiac screening in RA. On the other hand, the study was limited by i) the small sample size, ii) the single-center design, iii) the cross-sectional observational design, and iv) the lack of multivariate analysis to identify independent predictors of CVR in RA patients submitted to US.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, our findings show that inflammatory activity played a major role in subclinical cardiovascular dysfunction in a sample of RA patients. Hence, US screening of the heart and carotids should be considered for earlier detection and intervention, especiallly in subjects with active RA or additional CVRFs. Furter investigations are needed to explore the methods of early detection of CVRFs in RA.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to thank Funda\u0026ccedil;\u0026atilde;o Edson Queiroz for logistical support and assistance.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the finding of this study are available on a reasonable request from \u0026nbsp; \u0026nbsp;the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone to declare\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors received financial support from the SUS Research Program \u0026lsquo;Shared Management in Health\u0026rsquo;/PPSUS-CE-FUNCAP-SESA-Decit/SCTIE/MS-CNPq (02/2020). The investigators Paula Goes, Hell\u0026iacute;ada Vasconcelos Chaves and Mirna Marques Bezerra are affiliated with CNPq (National Council for Scientific and Technological Development). The investigator Vicente de Paulo Teixeira Pinto is affiliated with FUNCAP (Cear\u0026aacute; Foundation for Scientific and Technological Development).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eChristiane Aguiar Nobre:\u0026nbsp;\u003c/strong\u003eWriting \u0026ndash; review \u0026amp; editing, Writing \u0026ndash; original draft, Data curation, Validation, Resources, Project administration, Methodology, Investigation, Formal analysis. \u003cstrong\u003eCarlos Ewerton Maia Rodrigues:\u0026nbsp;\u003c/strong\u003eWriting \u0026ndash; review \u0026amp; editing, Writing- original draft, Formal analysis, Data curation, Conceptualization, Methodology. Investigation, Formal analysis.\u003cstrong\u003e\u0026nbsp;Luzia Keyne Sousa Carneiro Frota:\u0026nbsp;\u003c/strong\u003eData curation.\u003cstrong\u003e\u0026nbsp;Natacha Xavier Cavalcante\u003c/strong\u003e: Writing \u0026ndash; review \u0026amp; editing.\u003cstrong\u003e\u0026nbsp;Th\u0026aacute;cilla Siqueira Eug\u0026ecirc;nio Nascimento:\u0026nbsp;\u003c/strong\u003eMethodology\u003cstrong\u003e. Jo\u0026atilde;o Gabriel Marques Brayner:\u0026nbsp;\u003c/strong\u003eWriting \u0026ndash; review \u0026amp; editing.\u003cstrong\u003e\u0026nbsp;Giovanna Azevedo Sousa:\u0026nbsp;\u003c/strong\u003eData curation.\u003cstrong\u003e\u0026nbsp;Paula Goes:\u0026nbsp;\u003c/strong\u003eWriting \u0026ndash; review \u0026amp; editing, Writing \u0026ndash; original draft. \u003cstrong\u003eVicente de Paulo Teixeira Pinto:\u0026nbsp;\u003c/strong\u003eMethodology, Data curation. \u003cstrong\u003eHell\u0026iacute;ada Vasconcelos Chaves:\u0026nbsp;\u003c/strong\u003eWriting \u0026ndash; review \u0026amp; editing.\u003cstrong\u003e\u0026nbsp;Mirna Marques Bezerra:\u0026nbsp;\u003c/strong\u003eWriting \u0026ndash; review \u0026amp; editing, Writing \u0026ndash; original draft, Data curation, Conceptualization, Validation, Resources, Project administration, Methodology, Investigation, Formal analysis.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003ePujades-Rodriguez M, George J, van Staa TP, Stogiannis D, Rahman A, Smeeth L et al (2016) Rheumatoid arthritis and incidence of twelve initial presentations of cardiovascular disease: a population record-linkage cohort study in England. 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Arthritis Rheumatol 67:2311\u0026ndash;2322. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi:10.1002/art.39198\u003c/span\u003e\u003cspan address=\"https://doi:10.1002/art.39198\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"internal-and-emergency-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"iaem","sideBox":"Learn more about [Internal and Emergency Medicine](http://link.springer.com/journal/11739)","snPcode":"11739","submissionUrl":"https://www.editorialmanager.com/iaem/default.aspx","title":"Internal and Emergency Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Rheumatoid arthritis, Disease activity, Cardiovascular risk, Ultrasonography, Echocardiogram, Subclinical diastolic dysfunction","lastPublishedDoi":"10.21203/rs.3.rs-8090949/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8090949/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eRheumatoid arthritis (RA) is a chronic inflammatory disorder associated with cardiovascular risk (CVR), regardless of traditional risk factors. In this study we investigated the association between disease activity, CVR and cardiac and carotid ultrasound (US) findings in 60 RA patients and 60 age and sex-matched healthy controls. The clinical variables included epidemiological and laboratory data and disease activity scores (DAS28-PCR). CVR was stratified using SCORE/mSCORE and Framingham scores. The US methods employed (transthoracic echocardiography and Doppler carotid ecography) allowed to evaluate carotid intima-media thickness (CIMT), atherosclerosis plaque, and cardiac function. The female sex was predominant (RA\u0026thinsp;=\u0026thinsp;91.7%; controls\u0026thinsp;=\u0026thinsp;90%) and the mean age was 52\u0026thinsp;\u0026plusmn;\u0026thinsp;12 years and 52\u0026thinsp;\u0026plusmn;\u0026thinsp;13 years, respectively. The mean disease duration was 10.43\u0026thinsp;\u0026plusmn;\u0026thinsp;7.55 years. Serum testing for rheumatoid factor and anti-CCP was double-negative in 36.7%. The DAS28-PCR scores identified 61.7% as \u0026lsquo;remission/low activity\u0026rsquo; and 31.3% as \u0026lsquo;moderate/high activity\u0026rsquo;. CVR was similar in the two groups (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.261). When the echocardiographic data was stratified, diastolic dysfunction was significantly more prevalent in subjects with higher disease activity (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.04). In addition, high clinical CVR scores were associated with greater CIMT and carotid plaque (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Our results suggest that inflammatory activity may play a major role in subclinical cardiovascular dysfunction in RA.\u003c/p\u003e","manuscriptTitle":"Subclinical diastolic dysfunction and its association with disease activity in patients with rheumatoid arthritis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-04 09:05:58","doi":"10.21203/rs.3.rs-8090949/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"","date":"2026-01-02T07:59:11+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-12-02T09:10:35+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-17T03:56:09+00:00","index":"","fulltext":""},{"type":"submitted","content":"Internal and Emergency Medicine","date":"2025-11-15T17:05:37+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"internal-and-emergency-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"iaem","sideBox":"Learn more about [Internal and Emergency Medicine](http://link.springer.com/journal/11739)","snPcode":"11739","submissionUrl":"https://www.editorialmanager.com/iaem/default.aspx","title":"Internal and Emergency Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"d126b9a6-aae3-4429-bbab-438ae004cc00","owner":[],"postedDate":"December 4th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-21T05:10:00+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-04 09:05:58","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8090949","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8090949","identity":"rs-8090949","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}