Association between antibodies to carbamylated proteins and subclinical atherosclerosis in rheumatoid arthritis patients

Abstract Background Rheumatoid arthritis (RA) patients carry a high risk of cardiovascular morbidity and mortality. The excess of cardiovascular disease cannot be entirely explained by traditional risk factors and the immune system contributes to the development of atherosclerosis. Moreover, post-tr...

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Main Authors: Francesca Romana Spinelli, Arbi Pecani, Francesco Ciciarello, Tania Colasanti, Manuela Di Franco, Francesca Miranda, Fabrizio Conti, Guido Valesini, Cristiano Alessandri
Format: Article
Language:English
Published: BMC 2017-05-01
Series:BMC Musculoskeletal Disorders
Online Access:http://link.springer.com/article/10.1186/s12891-017-1563-8
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author Francesca Romana Spinelli
Arbi Pecani
Francesco Ciciarello
Tania Colasanti
Manuela Di Franco
Francesca Miranda
Fabrizio Conti
Guido Valesini
Cristiano Alessandri
author_facet Francesca Romana Spinelli
Arbi Pecani
Francesco Ciciarello
Tania Colasanti
Manuela Di Franco
Francesca Miranda
Fabrizio Conti
Guido Valesini
Cristiano Alessandri
author_sort Francesca Romana Spinelli
collection DOAJ
description Abstract Background Rheumatoid arthritis (RA) patients carry a high risk of cardiovascular morbidity and mortality. The excess of cardiovascular disease cannot be entirely explained by traditional risk factors and the immune system contributes to the development of atherosclerosis. Moreover, post-translational modifications such as citrullination and carbamylation have been linked to inflammation and atherosclerosis. Anti-carbamylated proteins antibodies (anti-CarP) are a new subset of autoantibodies identified in RA patients. This study aimed to investigate a possible association between anti-CarP and subclinical atherosclerosis in RA patients. Methods We enrolled RA patients and normal healthy controls (NHS) without known cardiovascular risk factors or heart disease. Cardiovascular risk was assessed using the Modified Systemic Coronary Risk Evaluation (mSCORE). Anti-CarP were investigated by a solid phase “home-made” ELISA. Anti-citrullinated protein antibodies (ACPA) and Rheumatoid Factor (RF) were investigated by ELISA assays. Subclinical atherosclerosis was evaluated by brachial artery Flow-Mediated Dilatation (FMD) and Carotid Intima-Media Thickness (c-IMT) while arterial stiffness by Ankle-Brachial Index (ABI) and Cardio-Ankle Vascular Index (CAVI). Results We enrolled 50 RA patients (34 F and 16 M, mean age 58.4 ± 13.1 years, mean disease duration 127 ± 96.7 months) and 30 age and sex matched NHS. According to the mSCORE, 58% of patients had a low risk, 32% a moderate and 8% a high risk for cardiovascular disease. FMD was significantly lower in RA patients than in NHS (5.6 ± 3.2 vs 10.7 ± 8.1%; p < 0.004) and CAVIs significantly higher in a RA patients compared to NHS (left CAVI 8.9 ± 1.7 vs 8.1 ± 1.5; p < 0.04 for and right CAVI 8.8 ± 1.6 vs 8.0 ± 1.4; p < 0.04 for the). ABI and c-IMT did not differ between the two populations. The multivariate regression analysis showed a significant association of anti-CarP antibodies with FMD, left and right CAVI and both c-IMT (r = 1.6 and p = 0.05; r = 1.7 and p = 0.04; r = 2.9 and p = 0.05; r = 1.5 and p = 0.03; r = 1.1 and p = 0.03 respectively). Conclusions This study confirms that RA patients, without evidence of cardiovascular disease or traditional risk factors, have an impaired endothelial function. Moreover, we found an association with anti-CarP antibodies suggesting a possible contribution of these autoantibodies to endothelial dysfunction, the earliest stage of atherosclerosis. Besides ultrasound assessment, anti-CarP should be assessed in RA patients and considered an additional cardiovascular risk factor.
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spelling doaj.art-0434428984614eeebb8d633cf34985af2022-12-22T03:17:11ZengBMCBMC Musculoskeletal Disorders1471-24742017-05-011811910.1186/s12891-017-1563-8Association between antibodies to carbamylated proteins and subclinical atherosclerosis in rheumatoid arthritis patientsFrancesca Romana Spinelli0Arbi Pecani1Francesco Ciciarello2Tania Colasanti3Manuela Di Franco4Francesca Miranda5Fabrizio Conti6Guido Valesini7Cristiano Alessandri8Department of Internal Medicine and Medical Specialties, Rheumatology, Sapienza University of RomeDepartment of Internal Medicine and Medical Specialties, Rheumatology, Sapienza University of RomeDepartment of Cardiovascular, Respiratory, Nephrology and Geriatrics Sciences, Sapienza University of RomeDepartment of Internal Medicine and Medical Specialties, Rheumatology, Sapienza University of RomeDepartment of Internal Medicine and Medical Specialties, Rheumatology, Sapienza University of RomeDepartment of Internal Medicine and Medical Specialties, Rheumatology, Sapienza University of RomeDepartment of Internal Medicine and Medical Specialties, Rheumatology, Sapienza University of RomeDepartment of Internal Medicine and Medical Specialties, Rheumatology, Sapienza University of RomeDepartment of Internal Medicine and Medical Specialties, Rheumatology, Sapienza University of RomeAbstract Background Rheumatoid arthritis (RA) patients carry a high risk of cardiovascular morbidity and mortality. The excess of cardiovascular disease cannot be entirely explained by traditional risk factors and the immune system contributes to the development of atherosclerosis. Moreover, post-translational modifications such as citrullination and carbamylation have been linked to inflammation and atherosclerosis. Anti-carbamylated proteins antibodies (anti-CarP) are a new subset of autoantibodies identified in RA patients. This study aimed to investigate a possible association between anti-CarP and subclinical atherosclerosis in RA patients. Methods We enrolled RA patients and normal healthy controls (NHS) without known cardiovascular risk factors or heart disease. Cardiovascular risk was assessed using the Modified Systemic Coronary Risk Evaluation (mSCORE). Anti-CarP were investigated by a solid phase “home-made” ELISA. Anti-citrullinated protein antibodies (ACPA) and Rheumatoid Factor (RF) were investigated by ELISA assays. Subclinical atherosclerosis was evaluated by brachial artery Flow-Mediated Dilatation (FMD) and Carotid Intima-Media Thickness (c-IMT) while arterial stiffness by Ankle-Brachial Index (ABI) and Cardio-Ankle Vascular Index (CAVI). Results We enrolled 50 RA patients (34 F and 16 M, mean age 58.4 ± 13.1 years, mean disease duration 127 ± 96.7 months) and 30 age and sex matched NHS. According to the mSCORE, 58% of patients had a low risk, 32% a moderate and 8% a high risk for cardiovascular disease. FMD was significantly lower in RA patients than in NHS (5.6 ± 3.2 vs 10.7 ± 8.1%; p < 0.004) and CAVIs significantly higher in a RA patients compared to NHS (left CAVI 8.9 ± 1.7 vs 8.1 ± 1.5; p < 0.04 for and right CAVI 8.8 ± 1.6 vs 8.0 ± 1.4; p < 0.04 for the). ABI and c-IMT did not differ between the two populations. The multivariate regression analysis showed a significant association of anti-CarP antibodies with FMD, left and right CAVI and both c-IMT (r = 1.6 and p = 0.05; r = 1.7 and p = 0.04; r = 2.9 and p = 0.05; r = 1.5 and p = 0.03; r = 1.1 and p = 0.03 respectively). Conclusions This study confirms that RA patients, without evidence of cardiovascular disease or traditional risk factors, have an impaired endothelial function. Moreover, we found an association with anti-CarP antibodies suggesting a possible contribution of these autoantibodies to endothelial dysfunction, the earliest stage of atherosclerosis. Besides ultrasound assessment, anti-CarP should be assessed in RA patients and considered an additional cardiovascular risk factor.http://link.springer.com/article/10.1186/s12891-017-1563-8
spellingShingle Francesca Romana Spinelli
Arbi Pecani
Francesco Ciciarello
Tania Colasanti
Manuela Di Franco
Francesca Miranda
Fabrizio Conti
Guido Valesini
Cristiano Alessandri
Association between antibodies to carbamylated proteins and subclinical atherosclerosis in rheumatoid arthritis patients
BMC Musculoskeletal Disorders
title Association between antibodies to carbamylated proteins and subclinical atherosclerosis in rheumatoid arthritis patients
title_full Association between antibodies to carbamylated proteins and subclinical atherosclerosis in rheumatoid arthritis patients
title_fullStr Association between antibodies to carbamylated proteins and subclinical atherosclerosis in rheumatoid arthritis patients
title_full_unstemmed Association between antibodies to carbamylated proteins and subclinical atherosclerosis in rheumatoid arthritis patients
title_short Association between antibodies to carbamylated proteins and subclinical atherosclerosis in rheumatoid arthritis patients
title_sort association between antibodies to carbamylated proteins and subclinical atherosclerosis in rheumatoid arthritis patients
url http://link.springer.com/article/10.1186/s12891-017-1563-8
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