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Management of Cardiovascular Disease Risk in Rheumatoid Arthritis

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Immunology".

Deadline for manuscript submissions: closed (15 December 2021) | Viewed by 15452

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Prof. Dr. Patrick H.M.C. Dessein

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Guest Editor

1. Departments of Medicine and Physiology, University of Witwatersrand, Johannesburg, South Africa
2. Rheumatology Unit, Free University Hospital, Faculty of Medicine and Pharmacy, Free University, Brussels, Belgium
Interests: rheumatoid arthritis; autoimmune disease; clinical rheumatology; autoantibodies; rheumatology; arthritis; cardiovascular risk

Prof. Dr. Miguel Angel Gonzalez-Gay

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Guest Editor

1. Head of Rheumatology Department, Hospital Universitario Marqués de Valdecilla de Santander, 39008 Santander, Cantabria, Spain
2. Department of Medicine, Universidad de Cantabria, 39005 Santander, Cantabria, Spain
Interests: rheumatic diseases; musculoskeletal disorders; rheumatoid arthritis inflammation; autoimmune disease; autoimmunity; psoriasis; cardiovascular; genetics; T lymphocytes
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Special Issue Information

Dear Colleagues,

Rheumatoid arthritis (RA) is a chronic inflammatory disease that causes mainly joint damage and increases the risk of cardiovascular disease (CVD) to a similar extent as diabetes. CVD in RA patients is associated with adverse traditional cardiovascular risk factor profiles, systemic inflammation, and their interactions, as well as genetic components. Additionally, medications used to treat disease activity, as well as population origin, impact CVD risk in RA patients. The increased atherogenesis that is experienced by RA patients awaits further elucidation. CVD risk assessment and prevention are currently suboptimal in RA patients.

This Special Issue aims to improve CVD risk management in the presence of RA. We therefore invite original basic science and clinical papers, meta-analyses, and state-of-the-art reviews that deal with atherogenic mechanisms, cardiovascular risk stratification, and the role of lifestyle modification, cardiovascular drugs, and antirheumatic agents in reducing CVD risk in RA patients.

Prof. Dr. Patrick H.M.C. Dessein
Prof. Dr. Miguel Angel Gonzalez-Gay
Guest Editors

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Keywords

Rheumatoid arthritis
Endothelial dysfunction
Atherosclerosis
Cardiac function
Arterial function
Cardiovascular events
Lifestyle factors
Antihypertensive agents
Lipid-lowering drugs
Antirheumatic agents

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Published Papers (7 papers)

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Editorial

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5 pages, 211 KiB

Open AccessEditorial

Management of Cardiovascular Disease Risk in Rheumatoid Arthritis

by Patrick H. Dessein and Miguel A. Gonzalez-Gay

J. Clin. Med. 2022, 11(12), 3487; https://doi.org/10.3390/jcm11123487 - 17 Jun 2022

Cited by 6 | Viewed by 1535

Abstract

Cardiovascular diseases, including ischemic heart disease and stroke, reportedly comprise the top two causes of global mortality [...] Full article

(This article belongs to the Special Issue Management of Cardiovascular Disease Risk in Rheumatoid Arthritis)

Research

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12 pages, 296 KiB

Open AccessArticle

Subclinical Atherosclerosis Measure by Carotid Ultrasound and Inflammatory Activity in Patients with Rheumatoid Arthritis and Spondylarthritis

by Marta Rojas-Giménez, Clementina López-Medina, María Lourdes Ladehesa-Pineda, María Ángeles Puche-Larrubia, Ignacio Gómez-García, Jerusalem Calvo-Gutiérrez, Pedro Seguí-Azpilcueta, María del Carmen Ábalos-Aguilera, Desirée Ruíz-Vilchez, Alejandro Escudero-Contreras and Eduardo Collantes-Estévez

J. Clin. Med. 2022, 11(3), 662; https://doi.org/10.3390/jcm11030662 - 27 Jan 2022

Cited by 3 | Viewed by 1662

Abstract

Objective: To compare the effect of inflammation on subclinical atherosclerosis using carotid ultrasound in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA). Methods: Cross-sectional study including 347 participants (148 RA, 159 SpA, and 40 controls). We measured the carotid intima media thickness (cIMT) and detection of atheromatous plaques using carotid ultrasound. We recorded disease activity (DAS28-CRP/ASDAS-CRP) and traditional cardiovascular risk factors. We performed descriptive, bivariate, and linear multivariate analyses (dependent variable: cIMT) to evaluate the influence of diagnosis on cIMT in all patients. Two additional multivariate analyses were performed by stratifying patients according to their inflammatory activity. Results: cIMT correlated with the mean CRP during the previous 5 years in RA, but not with CRP at the cut-off date. We did not find such differences in patients with SpA. The first multivariate model revealed that increased cIMT was more common in patients with RA than in those with SpA (β coefficient, 0.045; 95% confidence interval (95% CI), 0.0002–0.09; p = 0.048) after adjusting for age, sex, disease course, and differential cardiovascular risk factors (arterial hypertension, smoking, statins, and corticosteroids). The second model revealed no differences in cIMT between the 2 groups of patients classified as remission–low activity (β coefficient, 0.020; 95% CI, −0.03 to 0.080; p = 0.500). However, when only patients with moderate–high disease activity were analysed, the cIMT was 0.112 mm greater in those with RA (95% CI, 0.013–0.212; p = 0.026) than in those with SpA after adjusting for the same variables. Conclusions: Subclinical atherosclerosis measured by carotid ultrasound in patients with RA and SpA is comparable when the disease is well controlled. However, when patients have moderate–high disease activity, cIMT is greater in patients with RA than in those with SpA after adjusting for age, sex, disease course, and cardiovascular risk factors. Our results point to greater involvement of disease activity in subclinical atherosclerosis in patients with RA than in those with SpA. Full article

(This article belongs to the Special Issue Management of Cardiovascular Disease Risk in Rheumatoid Arthritis)

8 pages, 256 KiB

Open AccessArticle

Moderate and High Disease Activity Predicts the Development of Carotid Plaque in Rheumatoid Arthritis Patients without Classic Cardiovascular Risk Factors: Six Years Follow-Up Study

by Iván Ferraz-Amaro, Alfonso Corrales, Belén Atienza-Mateo, Nuria Vegas-Revenga, Diana Prieto-Peña, Ricardo Blanco and Miguel Á. González-Gay

J. Clin. Med. 2021, 10(21), 4975; https://doi.org/10.3390/jcm10214975 - 27 Oct 2021

Cited by 11 | Viewed by 1595

Abstract

Patients with rheumatoid arthritis (RA) have a higher incidence of subclinical atherosclerosis and cardiovascular (CV) disease. It is postulated that the appearance of accelerated atherosclerosis in these patients is a consequence of the inflammation present in the disease. In this study, we aim to determine if baseline disease activity in patients with RA predicts the future development of carotid plaque. A set of consecutive RA patients without a history of CV events, cancer or chronic kidney disease, who did not show carotid plaque in a carotid ultrasound assessment, were prospectively followed up for at least 5 years. At the time of recruitment, CV risk factors and disease-related data, including disease activity scores, were assessed. At the end of the follow-up, a carotid ultrasound was repeated and patients were divided into two groups; those who developed carotid plaque, and those who did not. A multivariable regression analysis was performed to define the predictors for the development of carotid plaque. One hundred and sixty patients with RA were followed up for an average of 6 ± 1 years. After this time, 66 (41%) of the patients had developed carotid plaque, and 94 (59%) did not. Patients with carotid plaque were significantly older (47 ± 13 vs. 55 ± 9 years, p < 0.001) at baseline, were more frequently diabetic (0% vs. 6%, p = 0.028), and had higher total cholesterol (197 ± 36 vs. 214 ± 40 mg/dL, p = 0.004) and LDL cholesterol (114 ± 35 vs. 126 ± 35 mg/dL, p = 0.037) at the beginning of the study. After multivariable adjustment, patients who were in the moderate and high disease activity (DAS28-CRP) categories displayed a higher odds ratio for the appearance of carotid plaque (OR 2.26 [95% CI 1.02–5.00], p = 0.044) compared to those in the DAS-28-CRP remission category. Remarkably, when patients were divided in patients within the low-risk SCORE category, and patients included in the remaining SCORE categories (moderate, high and very high), the relation between DAS28-CRP and the development of carotid plaque was only significant in the low-risk SCORE category. In conclusion, disease activity predicts the future development of subclinical atherosclerosis in patients with RA. Full article

(This article belongs to the Special Issue Management of Cardiovascular Disease Risk in Rheumatoid Arthritis)

11 pages, 3213 KiB

Open AccessArticle

Angiotensin-Inhibiting Drugs Do Not Impact Disease Activity in Patients with Rheumatoid Arthritis: A Retrospective Cross-Sectional Study

by Dorien M. C. F. Sluijsmans, Daphne C. Rohrich, Calin D. Popa and Bart J. F. van den Bemt

J. Clin. Med. 2021, 10(9), 1985; https://doi.org/10.3390/jcm10091985 - 5 May 2021

Cited by 4 | Viewed by 2024

Abstract

Objectives: Besides their proven effectivity in decreasing the risk of cardiovascular events, angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II type 1 receptor blockers (ARBs) are likely to possess anti-inflammatory properties as well. This study aims to investigate whether the use of ACEi and ARBs additionally lowers disease activity in patients with rheumatoid arthritis (RA). Methods: In this cross-sectional study, we used ARBs or ACEi to study RA patients who had at least one DAS28-CRP measurement during a one-year period. A control group of RA patients without ACEi/ARBs was randomly selected. The primary outcome was the difference between the DAS28-CRP scores of ACEi/ARBs users and controls. The secondary outcomes were the differences between administered dosages of csDMARDs and bDMARDs for users and controls, respectively; these were expressed in defined daily dose (DDD). Confounders were included in the multiple regression analyses. Results: A total of 584 ACEi/ARBs users and 552 controls were finally examined. Multiple linear regression analyses showed no association between the use of ACEi or ARBs and the DAS28-CRP scores (ACEi factor 1.00, 95% CI 0.94–1.06; ARBs 1.02, 95% CI 0.96–1.09), nor with the dosage of csDMARDs (ACEi 0.97, 95% CI 0.89–1.07; ARBs 0.99, 95% CI 0.90–1.10). Furthermore, the use of ACEi was not associated with reduced dosages of bDMARDs (OR 1.14, 95% CI 0.79–1.64), whereas ARBs users tended to use less bDMARDs (1.46, 95% CI 0.98–2.18, p = 0.06). Conclusion: In this study, the use of either ACEi or ARBs in RA patients had no impact on disease activity as measured by the DAS28-CRP. A trend towards lower bDMARD dosages was observed in ARBs users, but the significance of this finding is still unclear. Full article

(This article belongs to the Special Issue Management of Cardiovascular Disease Risk in Rheumatoid Arthritis)

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11 pages, 296 KiB

Open AccessArticle

Body Mass Index and Disease Activity in Chronic Inflammatory Rheumatic Diseases: Results of the Cardiovascular in Rheumatology (Carma) Project

by Jesús A. Valero-Jaimes, Ruth López-González, María A. Martín-Martínez, Carmen García-Gómez, Fernando Sánchez-Alonso, Jesús T. Sánchez-Costa, Carlos González-Juanatey, Eva Revuelta-Evrad, César Díaz-Torné, Cruz Fernández-Espartero, Carolina Pérez-García, Vicenç Torrente-Segarra, Ginés Sánchez-Nievas, Trinidad Pérez-Sandoval, Pilar Font-Ugalde, María L. García-Vivar, Elena Aurrecoechea, Olga Maiz-Alonso, Ramón Valls-García, José A. Miranda-Filloy, Javier Llorca, Santos Castañeda and Miguel A. Gonzalez-Gay Show full author list Hide full author list

J. Clin. Med. 2021, 10(3), 382; https://doi.org/10.3390/jcm10030382 - 20 Jan 2021

Cited by 11 | Viewed by 2851

Abstract

Objective: Since obesity has been associated with a higher inflammatory burden and worse response to therapy in patients with chronic inflammatory rheumatic diseases (CIRD), we aimed to confirm the potential association between body mass index (BMI) and disease activity in a large series of patients with CIRDs included in the Spanish CARdiovascular in rheuMAtology (CARMA) registry. Methods: Baseline data analysis of patients included from the CARMA project, a 10-year prospective study of patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA) attending outpatient rheumatology clinics from 67 Spanish hospitals. Obesity was defined when BMI (kg/m²) was >30 according to the WHO criteria. Scores used to evaluate disease activity were Disease Activity Score of 28 joints (DAS28) in RA, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in AS, and modified DAS for PsA. Results: Data from 2234 patients (775 RA, 738 AS, and 721 PsA) were assessed. The mean ± SD BMI at the baseline visit were: 26.9 ± 4.8 in RA, 27.4 ± 4.4 in AS, and 28.2 ± 4.7 in PsA. A positive association between BMI and disease activity in patients with RA (β = 0.029; 95%CI (0.01–0.05); p = 0.007) and PsA (β = 0.036; 95%CI (0.015–0.058); p = 0.001) but not in those with AS (β = 0.001; 95%CI (−0.03–0.03); p = 0.926) was found. Disease activity was associated with female sex and rheumatoid factor in RA and with Psoriasis Area Severity Index and enthesitis in PsA. Conclusions: BMI is associated with disease activity in RA and PsA, but not in AS. Given that obesity is a potentially modifiable factor, adequate control of body weight can improve the outcome of patients with CIRD and, therefore, weight control should be included in the management strategy of these patients. Full article

(This article belongs to the Special Issue Management of Cardiovascular Disease Risk in Rheumatoid Arthritis)

9 pages, 767 KiB

Open AccessArticle

The Performance of Vascular Age in the Assessment of Cardiovascular Risk of Patients with Rheumatoid Arthritis

by Iván Ferraz-Amaro, Alfonso Corrales, Juan Carlos Quevedo-Abeledo, Belén Atienza-Mateo, Diana Prieto-Peña, Ricardo Blanco, Javier Llorca and Miguel Á. González-Gay

J. Clin. Med. 2020, 9(12), 4065; https://doi.org/10.3390/jcm9124065 - 16 Dec 2020

Cited by 2 | Viewed by 1840

Abstract

Background. Cardiovascular (CV) disease risk prediction models developed for use in the general population have suboptimal performance in patients with rheumatoid arthritis (RA). Vascular age (VA) is a new concept that has been proposed as a measure of CV ‘relative’ risk instead of the ‘absolute’ risk that current prediction models provide. In the present study we aim to study the performance of vascular age (VA) in the assessment of CV risk in patients with RA. We additionally aimed to analyze its relation with subclinical atherosclerosis as measured through carotid plaque ultrasound. Methods. A total of 1173 non-diabetic RA patients without previous CV events were included. Disease characteristics, SCORE, VA determined on SCORE and on carotid intima media thickness (cIMT), and the presence of plaque through carotid ultrasound were assessed. The interrelations of VA with SCORE, and its associations with subclinical carotid atherosclerosis were studied. Results. On average, RA patients had both a SCORE determined VA (4.7 years) and a cIMT-based VA (2.4 years) significantly higher than the chronological age. When these differences were analyzed in different age intervals, while VA based on SCORE was significantly higher compared to chronological age in all age ranges, VA determined on cIMT was significantly elevated only in RA patients younger than 60 years. The area under the curve analysis for the association of SCORE and VA with the presence of carotid plaque disclosed no differences between both parameters. VA was associated with the presence of carotid plaque after multivariable regression analysis in patients younger than 60 years old. Conclusion. VA is significantly higher than chronological age in patients with RA. The performance of VA in its relation to carotid plaque is similar to that of the SCORE. Full article

(This article belongs to the Special Issue Management of Cardiovascular Disease Risk in Rheumatoid Arthritis)

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Review

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11 pages, 282 KiB

Open AccessReview

Cardiovascular Disease Risk in Rheumatoid Arthritis Anno 2022

by Bas Dijkshoorn, Reinder Raadsen and Michael T. Nurmohamed

J. Clin. Med. 2022, 11(10), 2704; https://doi.org/10.3390/jcm11102704 - 11 May 2022

Cited by 27 | Viewed by 3170

Abstract

The risk for developing cardiovascular diseases (CVD) in rheumatoid arthritis (RA) patients is 1.5 times higher compared to the general population. This risk is partly due to the contribution of systemic inflammation in increased atherogenesis, while an increased prevalence of “traditional” cardiovascular risk factors, such as hypertension and dyslipidemia, is also attributed to nearly 50% of the total CVD risk. Most anti-rheumatic medication partly reduces this CVD risk, primarily by reducing inflammation. The increased risk is recognized by most guidelines, which advise consequent screening and multiplying calculated risk scores by 1.5. However, screening in daily clinical practice is poorly done, and RA patients often have undiagnosed and untreated risk factors. In conclusion, even nowadays, RA patients still have an increased risk of developing CVD. Advances in anti-inflammatory treatment partly mitigate this risk, but RA patients need mandatory screening for CV risk factors to turn their CVD risk towards that of the general population. Full article

(This article belongs to the Special Issue Management of Cardiovascular Disease Risk in Rheumatoid Arthritis)

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