Search

Background: Aortic stiffness index (AoSI) has to be considered a proxy outcome measure in patients with rheumatoid arthritis (RA). The aim of this study was to comparatively describe AoSI progression in two groups of RA patients on long-term treatment with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) with or without tumour necrosis factor inhibitors (TNFi)., Methods: AoSI was evaluated by Doppler echocardiography at the level of the aortic root, using a two-dimensional guided M-mode evaluation. Eligible participants were assessed at baseline and after 12 months. Changes in serum lipids, glucose and arterial blood pressure were assessed. All patients who did not change DMARD treatment during follow-up were consecutively selected for this study., Results: We included 107 (64 TNFi and 43 csDMARDs) RA patients. Most patients (74%) were in remission or low disease activity and had some CVD risk factors (45.8% hypertension, 59.8% dyslipidaemia, 45.3% smoking). The two groups did not differ significantly for baseline AoSI (5.95±3.73% vs 6.08±4.20%, p=0.867). Follow-up AoSI was significantly increased from baseline in the csDMARDs group (+1.00%; p<0.0001) but not in the TNFi group (+0.15%, p=0.477). Patients on TNFi had significantly lower follow-up AoSI from baseline than the csDMARDs group (-1.02%, p<0.001; ANCOVA corrected for baseline AoSI, age and systolic blood pressure). Furthermore, follow-up AoSI was significantly lower in TNFi than in csDMARDs users with an increasing number of CVD risk factors., Conclusion: Long-term treatment with TNFi was associated with reduced aortic stiffness progression in patients with established RA and several CVD risk factors.

Systemic chronic inflammation may favor the onset of metabolic syndrome (MetS) which represents a risk factor for CV events. Rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are disorders with high prevalence of MetS. We assessed the factors associated with MetS and its prognostic role in non-selected RA/AS/PsA patients. Between March 2014 and April 2016, 458 patients (228 RA, 134 PsA, 96 AS) selected for a primary prevention program for cardiovascular diseases were analyzed. Primary and co-primary end points were a composite of all-cause death/all-cause hospitalization and CV death/CV hospitalization, respectively. MetS was diagnosed according to the IDF Task Force on Epidemiology and Prevention. Patients were divided into MetS + (73 = 16%) and MetS - (385 = 84%). At multivariate logistic analysis, cancer, moderate/high disease activity, higher LV mass (LVM) and degree of LV diastolic dysfunction were independently associated with MetS. At 36-month follow-up, the event rate for primary/co-primary end point was 52/15% in MetS + vs 23/7% in MetS - (both p < 0.001). At multivariate Cox regression analysis, MetS was related to primary end point (HR 1.52 [CI 1.01-2.47], p = 0.04) together with higher LVM, disease duration and higher prevalence of biologic DMARDs refractoriness, and to co-primary end point (HR 2.05 [CI 1.16-3.60], p = 0.01) together with older age and higher LVM. The RA/AS/PsA phenotype MetS + is a subject with moderate/high disease activity, LV structural and functional abnormalities at increased risk for cancer. MetS + identifies RA/AS/PsA patients at higher risk for CV and non-CV events, independently of traditional CV risk factors analyzed individually and traditional indexes of inflammation.

Introduction: Patients with rheumatoid arthritis (RA) develop early changes in left ventricular (LV) geometry and experience cardiovascular events in excess than in the general population. This study was designed to assess prevalence, predictors and prognostic role of LV hypertrophy (LVH) in a selected group of RA patients with normal blood pressure and glycemia who should be at low risk for LVH., Methods: We prospectively analyzed 241 normotensive normoglycemic RA patients (mean age 53 ± 12 years, 61% women) involved in a primary prevention program for cardiovascular diseases who were followed-up for 40 (24-56) months. LVH was detected by echocardiography and defined as LV mass ≥49.2 g/m 2.7 for men and ≥46.7 g/m 2.7 for women. Primary outcome was a composite of cardiovascular death/hospitalization., Results: LVH was detected in 39 patients (16%). Older age (>53 years), greater body mass index (BMI > 25 kg/m 2 ), longer duration of RA disease, anti-cyclic citrullinated peptide antibody (ACPA) positivity and concentric LV geometry were the variables associated with LVH. During the follow-up, a cardiovascular event occurred in 12 of 39 (31%) patients with LVH and in 22 of 202 (11%; P < .001) patients without LVH. LVH independently predicted cardiovascular events (hazards ratio 3.28 [95% CI 1.03-9.20], P = .03) at Cox regression analysis together with C-reactive protein and ACPA positivity., Conclusions: Nearly one-sixth of normotensive normoglycemic RA patients analyzed in a primary prevention program for cardiovascular diseases has LVH which is associated with obesity and older age, and strongly predicts cardiovascular event in these subjects., (© 2021 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Patients with rheumatoid arthritis (RA) have an increased incidence of cardiovascular events. Ultrasound examination of the carotid arteries can show the presence of plaques and detect the atherosclerotic subclinical process through the evaluation of intima-media thickness (cIMT) and carotid segmental distensibility (cCD). The aim of the present study was to identify which factors could independently influence the evolution of atherosclerosis (plaques, cIMT, and cCD) after 1 year of follow-up in a sample of patients with RA. A total of 137 patients with RA without previous cardiovascular (CV) events were enrolled at baseline, and 105 (M/F: 21/84, age 59.34 ± 11.65 years) were reassessed after one year using ultrasound of carotid arteries to detect atheromatous plaques and to measure cIMT and cCD. After one year, all the indices of subclinical atherosclerosis worsened with respect to baseline (Δ-cIMT = 0.030 ± 0.10 mm, p = 0.005; Δ-cCD = -1.64 ± 4.83, 10-3/KPa, p = 0.005; Δ-plaques = 8.6%, p = 0.035). Traditional CV risk factors (age, mean arterial pressure, and diabetes) and corticosteroid therapy were independently associated with the worsening of subclinical atherosclerosis. Interestingly, when considering RA patients divided according to the degree of disease activity score 28 with C-reactive protein (DAS28 [CRP] ≥2.6), the worsening of subclinical atherosclerosis indices was detectable exclusively in the group of patients with active disease. Our longitudinal study supports the hypothesis of a key role of both traditional CV risk factors and the inflammatory activity of arthritic disease in the progression of subclinical atherosclerosis in RA patients. In addition, corticosteroids might have a deleterious effect.

Objectives: Patients with rheumatoid arthritis (RA) are exposed to impairment in left ventricular (LV) function, which is a prognosticator of poorer clinical outcomes. In this study we assessed prevalence and factors associated with adverse outcomes in patients with RA and asymptomatic LV systolic dysfunction (LVSD)., Methods: We prospectively analysed 102 RA patients with asymptomatic LVSD consecutively selected by a pool of 418 RA patients referred to the Division of Rheumatology, University of Verona, between March 2014 and March 2015. LVSD was defined as impaired global longitudinal strain (GLS) measured by echocardiography. The pre-specified study end-points were all-cause death/hospitalisation, and death/hospitalisation for cardiovascular cause., Results: During a follow-up of 35 [13-54] months, all-cause death/hospitalisation occurred in 40 patients (39%). No patient died during the follow-up, 18 patients (18% of the study population) had a cardiovascular event which required hospitalisation, while 22 (22% of patients) required hospitalisation, but this was unrelated to CV. Multiple Cox regression analysis identified worse renal function, more frequent use and a higher number of biologic DMARDs used before enrolment as independent predictors of all-causes hospitalisation. The same variables together with higher LV mass predicted CV hospitalisation. Prognostic cut-off points were 90 ml/min/1.73 m2 for glomerular filtration rate and 49 g/m2.7 for LV mass., Conclusions: RA patients with asymptomatic LVSD have a very high rate of all-cause and cardiovascular hospitalisation at mid-term follow-up, predicted by worse renal function, higher LV mass, more frequent use and higher number of biologic DMARDs used before enrolment, suggesting that biologic DMARDs refractory is a proxy of adverse events.

Rheumatoid arthritis (RA) is associated with higher risk of heart failure. Several studies report that left ventricular (LV) diastolic dysfunction (LVDD), a silent precursor of heart failure, is widely present in RA patients. Very little is known about the factors related to the development of LVDD in this disease. In this study we assessed the incidence and the predictors of new-onset LVDD in RA patients. Two-hundred-ninety-five adults with RA without overt cardiac disease were prospectively analyzed from March 2014 to March 2015 by Doppler echocardiography. Among the 295 subjects evaluated, 217 (73.6%) had normal LV diastolic function and represented the final study population. At 1-year follow-up, 53 of 217 patients (24%) developed LVDD, which was of degree I (mild dysfunction) in all of them. By multivariate logistic regression analysis, lower E/A ratio of transmitral flow (ratio between the peak velocity of early diastolic "E" wave and late diastolic "A" wave of transmitral flow) was independently associated with new-onset LVDD [OR 0.17 (CI 0.09-0.57)], together with older age and higher systolic blood pressure. In a clinical predictive model derived from multivariate analysis, the new-onset LVDD rate event ranged from 0% (patients without any factor) to 75% (patients in whom the three predictors coexisted). A significant portion of patients with RA without overt cardiac disease develop LVDD at 1-year follow-up. This condition can be predicted by a simple clinical model which could improve the clinical management and the prognostic stratification of patients with RA.

Background: Due to chronic inflammatory status, rheumatoid arthritis (RA) patients are exposed to changes in left ventricular (LV) geometry and function. We assessed prevalence, factors associated with, and prognostic role of concentric LV geometry and systolic dysfunction (LVSD) detected by echocardiography in a large cohort of patients with RA and normal blood pressure., Hypothesis: Changes in LV geometry and function are widely detectable in normotensive patients with RA analyzed in primary prevention., Methods: We prospectively analyzed 194 normotensive RA patients without overt cardiac disease recruited between March 2014 and May 2016, compared with 194 non-RA matched controls. Relative wall thickness >0.43 defined concentric LV geometry. LVSD was defined as impaired global longitudinal strain (GLS). The prespecified study endpoints were all-cause hospitalization and hospitalization for cardiovascular cause., Results: The 194 normotensive subjects (mean age, 54 years; 63% female; RA duration 13 years) had a prevalence of LV concentric geometry 5-fold higher and LVSD 5-fold higher than non-RA matched controls. Body mass index, LVSD, and diastolic dysfunction were associated with concentric LV geometry, while worsening renal function and older age were associated with LVSD. LVSD was independently related to the study endpoints (HR 2.37 [1.24-4.53], p = 0.009, for all-causes hospitalization and HR 6.60 [1.47-29.72], p = 0.01 for cardiovascular hospitalization)., Conclusions: Despite normotensive status, a consistent proportion of RA patients analyzed in primary prevention have cardiac abnormalities detectable by echocardiography. LVSD is a strong prognosticator of adverse outcome at midterm period in these patients., (© 2018 Wiley Periodicals, Inc.)

Background: Speckle-tracking echocardiography allows early detection of subclinical left ventricular systolic dysfunction (LVSD) in patients with rheumatoid arthritis (RA). In this prospective study, we assessed the prevalence and the prognostic role of subclinical LVSD detected by speckle-tracking echocardiography in RA patients., Methods: Two-dimensional global longitudinal strain (GLS) and global circumferential strain (GCS) were measured in 209 RA patients without overt cardiac disease. LVSD was defined as low GLS (> -16.0%), low GCS (> -17.8%), or both. The primary end point was all-causes hospitalization; the coprimary end point was hospitalization for cardiovascular causes., Results: The study population had a mean age of 58 ± 11 years; 67% were female, 52% had hypertension, and the RA duration was 14 ± 10 years. Low GLS was detected in 51 patients (24%), low GCS in 42 patients (20%), and combined low GLS and GCS in 18 patients (9%). During a median follow-up time of 16 months (range, 10-21 months), a primary end point occurred in 50 patients (24%), and 25 patients were hospitalized for a cardiovascular event. Multiple Cox regression analyses revealed that combined low GLS and GCS was independently associated with the end point defined as all-causes hospitalization together with higher aortic stiffness. Examined individually, neither low GCS nor low GLS showed an independent association with this typology of clinical outcome. Conversely, both low GCS and low GLS (examined individually or as combined low GLS and GCS) emerged as strong independent prognosticators of cardiovascular events., Conclusions: Subclinical LVSD defined as low GLS, GCS, or both is common in RA patients without overt cardiac disease and provides additional prognostic information in these individuals., (Copyright © 2017 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Objectives: Ascending aorta has an increased stiffness (AoSI) in rheumatoid arthritis (RA) patients due to their chronic inflammatory status. We assessed prevalence and factors associated with increased AoSI and its prognostic role in a large cohort of RA patients., Methods: We prospectively analysed 226 RA patients without overt cardiac disease compared with 226 non-RA patients matched for cardiovascular risk factors (non-RA controls). Abnormally high AoSI was diagnosed if AoSI > 6.07% (95th percentile of the AoSI detected in our reference healthy population). AoSI was assessed at the level of the aortic root by two-dimensional guided M-mode evaluation as part of a thorough echocardiography performed in all patients., Results: AoSI was significantly higher in the RA patients than non-RA controls (6.3 ± 4.5% vs. 4.6 ± 3.5%, p < 0.001); it was related to older age, higher systolic blood pressure and RA disease. Predictors of AoSI in RA patients were older age, higher systolic blood pressure and the non-prescription of non-steroidal anti-inflammatory drug and/or immunomodulatory/anti-cytotoxic agents. Abnormally high AoSI was diagnosed in 41% RA patients and 21% non-RA controls (p < 0.001). The RA phenotype with abnormally high AoSI was a > 60 years old subject with systolic blood pressure > 129 mmHg, mitral annular calcification who was not receiving non-steroidal anti-inflammatory drug. By multivariate Cox regression analysis abnormally high AoSI independently predicted death or all-cause hospitalization (hazard ratio 2.85 (95% confidence interval 1.03-7.85)) at 12-month follow-up., Conclusions: Increased AoSI is common, can be predicted by an ordinary clinical assessment and is a strong predictor of adverse clinical outcome at mid-term follow-up in patients with RA., (© The European Society of Cardiology 2016.)

Background: Patients with rheumatoid arthritis have an increased risk for cardiovascular disease. Because of accelerated atherosclerosis and changes in left ventricular (LV) geometry, circumferential and longitudinal (C&L) LV systolic dysfunction (LVSD) may be impaired in these patients despite preserved LV ejection fraction. The aim of this study was to determine the prevalence of and factors associated with combined C&L LVSD in patients with rheumatoid arthritis., Methods: One hundred ninety-eight outpatients with rheumatoid arthritis without overt cardiac disease were prospectively analyzed from January through June 2014 and compared with 198 matched control subjects. C&L systolic function was evaluated by stress-corrected midwall shortening (sc-MS) and tissue Doppler mitral annular peak systolic velocity (S'). Combined C&L LVSD was defined if sc-MS was <86.5% and S' was <9.0 cm/sec (the 10th percentiles of sc-MS and S' derived in 132 healthy subjects)., Results: Combined C&L LVSD was detected in 56 patients (28%) and was associated with LV mass (odds ratio, 1.03; 95% CI, 1.01-1.06; P = .04) and concentric LV geometry (odds ratio, 2.76; 95% CI, 1.07-7.15; P = .03). By multiple logistic regression analysis, rheumatoid arthritis emerged as an independent predictor of combined C&L LVSD (odds ratio, 2.57; 95% CI, 1.06-6.25). The relationship between sc-MS and S' was statistically significant in the subgroup of 142 patients without combined C&L LVSD (r = 0.40, F < 0.001), having the best fitting by a linear function (sc-MS = 58.1 + 3.34 × peak S'; r(2) = 0.19, P < .0001), absent in patients with combined C&L LVSD., Conclusions: Combined C&L LVSD is detectable in about one fourth of patients with asymptomatic rheumatoid arthritis and is associated with LV concentric remodeling and hypertrophy. Rheumatoid arthritis predicts this worrisome condition, which may explain the increased risk for cardiovascular events in these patients., Notice of Clarification: The aim of this "notice of clarification" is to analyze in brief the similarities and to underline the differences between the current article (defined as "paper J") and a separate article entitled "Prevalence and Factors Associated with Subclinical Left Ventricular Systolic Dysfunction Evaluated by Mid-Wall Mechanics in Rheumatoid Arthritis" (defined as "paper E"), which was written several months before paper J, and recently accepted for publication by the journal "Echocardiography" (Cioffi et al. http://dx.doi.org/10.1111/echo.13186). We wish to explain more clearly how the manuscript described in "paper J" relates to the "paper E" and the context in which it ought to be considered. Data in both papers were derived from the same prospective database, so that it would appear questionable if the number of the enrolled patients and/or their clinical/laboratory/echocardiographic characteristics were different. Accordingly, both papers reported that 198 patients with rheumatoid arthritis (RA) were considered and their characteristics were identical, due to the fact that they were the same subjects (this circumstance is common and mandatory among all studies in which the patients were recruited from the same database). These are the similarities between the papers. In paper E, which was written several months before paper J, we focused on the prevalence and factors associated with impaired circumferential left ventricular (LV) systolic function measured as mid-wall shortening (corrected for circumferential end-systolic stress). We found that 110 patients (56% of the whole population) demonstrated this feature. Thus, these 110 patients were the object of the study described in paper E, in which we specifically analyzed the factors associated with the impairment of stress-corrected mid-wall shortening (sc-MS). The conclusions of that paper were: (i) subclinical LV systolic dysfunction (LVSD) is detectable in more than half RA population without overt cardiac disease as measured by sc-MS, (ii) RA per se is associated with LVSD, and (iii) in RA patients only LV relative wall thickness was associated with impaired sc-MS based upon multivariate logistic regression analysis. Differently, in the paper J, we focused on the prevalence and factors associated with combined impairment of circumferential and longitudinal shortening (C&L) in 198 asymptomatic patients with RA. We found that 56 patients (28% of the whole population) presented this feature. Thus, these 56 patients were analyzed in detail in this study, as well as the factors associated with the combined impairment of C&L shortening. In paper J, we evaluated sc-MS as an indicator of circumferential systolic LV shortening, and we also determined the average of tissue Doppler measures of maximal systolic mitral annular velocity at four different sampling sites ( S') as an indicator of longitudinal LV systolic shortening. This approach clearly demonstrates that in paper J, we analyzed data deriving from the tissue Doppler analysis, which were not taken into any consideration in paper E. The investigation described in paper J made evident several original and clinically relevant findings. In patients with RA: (i) the condition of combined C&L left ventricular systolic dysfunction (LVSD) is frequent; (ii) these patients have comparable clinical and laboratory characteristics with those without combined C&L LVSD, but exhibit remarkable concentric LV geometry and increased LV mass, a phenotype that can be consider a model of compensated asymptomatic chronic heart failure; (iii) RA is an independent factor associated with combined C&L LVSD; (iv) no relationship between indexes of circumferential and longitudinal function exists in patients with combined C&L LVSD, while it is statistically significant and positive when the subgroup of patients without combined C&L LVSD is considered, having the best fitting by a linear function. All these findings are unique to the paper J and are not presented (they could not have been) in paper E. It appears clear that, starting from the same 198 patients included in the database, different sub-groups of patients were selected and analyzed in the two papers (they had different echocardiographic characteristics) and, consequently, different factors emerged by the statistical analyses as covariates associated with the different phenotypes of LVSD considered. Importantly, both papers E and J had a very long gestation because all reviewers for the different journals found several and important issues that merited to be addressed: a lot of changes were proposed and much additional information was required, particularly by the reviewers of paper E. Considering this context, it emerges that although paper E was written well before paper J, the two manuscripts were accepted at the same time (we received the letters of acceptance within a couple of weeks). Thus, the uncertainty about the fate of both manuscripts made it very difficult (if not impossible) to cite either of them in the other one and, afterward, we just did not think about this point anymore. Of note, the idea to combine in the analysis longitudinal function came therefore well after the starting process of revision of the paper E and was, in some way inspired by a reviewer's comment. That is why we did not put both findings in the same paper. We think that our explanations provide the broad audience of your journal a perspective of transparency and our respect for the readers' right to understand how the work described in the paper J relates to other work by our research group. Giovanni Cioffi On behalf of all co-authors Ombretta Viapiana, Federica Ognibeni, Andrea Dalbeni, Davide Gatti, Carmine Mazzone, Giorgio Faganello, Andrea Di Lenarda, Silvano Adami, and Maurizio Rossini., (Copyright © 2016 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Background: Patients with rheumatoid arthritis (RA) have a high risk for cardiovascular disease due to a chronic inflammatory state, accelerated atherosclerosis, and changes in left ventricular (LV) geometry. These conditions predispose patients to LV systolic dysfunction (LVSD). In this study we assessed whether RA is a condition associated with LVSD, and analyzed the prevalence and factors associated with LVSD in patients with RA., Patients and Methods: Echocardiographic and clinical data from 198 patients with RA without presence or history of symptoms of cardiac disease were compared with 198 non-RA controls matched for cardiovascular risk factors. LVSD was identified with tissue Doppler echocardiography (TDE) when mitral annular peak systolic velocity (S') was < 9.0 cm/s., Results: Patients with RA were 61 ± 12 years old and 71 % were female (disease duration 14 ± 10 years). LVSD was found in 89 patients with RA (45 %). By multiple regression analysis including both RA patients and controls, RA emerged as an independent condition associated with LVSD (exp β 3.89; CI: 1.87-8.08) together with higher E/E' ratio (index of LV diastolic function) and diabetes mellitus. For the 198 patients with RA, the variables associated with LVSD were higher E/E' ratio and systolic blood pressure., Conclusions: Almost half of asymptomatic RA patients without history of cardiac disease have subclinical LVSD easily detectable with TDE. RA is closely related to LVSD. A higher degree of LV diastolic dysfunction and systolic blood pressure are associated with LVSD in these patients, whose risk for cardiovascular events could be better defined using such information in the asymptomatic stage of cardiac disease.

Objectives: Due to the chronic inflammatory status, specific neuro-hormones and progression of arterial stiffness, patients with rheumatoid arthritis (RA) are exposed to the development of excessive left ventricular mass disproportionate to the need to compensate left ventricular load. This condition, named inappropriately high left ventricular mass (iLVM), is associated with unfavorable prognosis in patients with hypertension, aortic stenosis or diabetes. In this study, we assessed prevalence and factors associated with iLVM in a large cohort of patients with RA and tested the hypothesis that RA per se is a condition related to iLVM., Methods: We prospectively analyzed 235 RA patients without overt cardiac disease recruited between January and December 2014, who were compared with 235 controls matched for age, sex, BMI, prevalence of hypertension and diabetes. iLVM was defined as measured/predicted LVM ratio above 123%. LVM was predicted in each individual by using a simple equation considering height, sex and left ventricular work., Results: iLVM was detected in 150 RA patients (64%) and in 30 controls (15%; P < 0.001). In patients with RA, the variables independently associated with iLVM emerged by multivariate logistic regression analysis were left ventricular systolic dysfunction measured as mid-wall shortening and concentric left ventricular geometry. Considering both groups of patients with RA and matched controls, RA was the strongest variable related to iLVM (odds ratio 3.37, 95% confidence interval 1.37-8.31, P = 0.008)., Conclusions: Two-thirds of patients with RA without overt cardiac disease have iLVM, which is associated with left ventricular systolic dysfunction and concentric geometry. RA per se is a condition closely related to iLVM.