Asymmetric dimethylarginine and vascular injury in rheumatoid arthritis, from capillaries to large vessels: results from a cross-sectional study
Angeloudi, Elena Anyfanti, Panagiota Gavriilaki, Eleni Pagkopoulou, Eleni Spanou, Kyriaki-Vasileia Bekiari, Eleni Doumas, Michael Dimitriadou, Vasiliki Kitas, George D Dimitroulas, Theodoros
Angeloudi, Elena
Anyfanti, Panagiota
Gavriilaki, Eleni
Pagkopoulou, Eleni
Spanou, Kyriaki-Vasileia
Bekiari, Eleni
Doumas, Michael
Dimitriadou, Vasiliki
Kitas, George D
Dimitroulas, Theodoros
Abstract
INTRODUCTION: Rheumatoid arthritis (RA) is associated with elevated cardiovascular risk. Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor and marker of endothelial dysfunction, has been implicated in inflammation-driven vascular injury. However, the association between ADMA and micro- and macrovascular function in RA remains unclear.
METHODS: Patients with RA underwent nailfold videocapillaroscopy (NVC) to assess microvascular alterations in the dermal capillary network. Macrovascular function was evaluated with well-known markers of arterial stiffness [carotid-femoral pulse wave velocity (PWV), augmentation index], and subclinical atherosclerosis [carotid intima-media thickness]. Serum ADMA was measured using enzyme-linked immunosorbent assay (ELISA).
RESULTS: A total of 103 consecutive RA patients (61.1 ± 11.6 years, 76.7% female) were studied with median disease duration 6 (12) years. Patients were under methotrexate (54.4%), corticosteroids (35.9%) and biologics (38.8%). A considerable portion had been previously diagnosed with hypertension (38.8%) and dyslipidemia (31.1%), and 41.7% were smokers. ADMA was not significantly associated with cardiovascular risk factors or markers of vascular injury in the total cohort. However, in the subgroup of patients not receiving cardiovascular medication (n = 48), ADMA significantly correlated with PWV, venous limb diameter and capillary tortuosity, even after adjustment for other variables in multivariate analysis.
CONCLUSIONS: Circulating ADMA was not associated with markers of vascular impairment in a real-life RA cohort presenting with various treatments and comorbidities. However, ADMA independently correlated with arterial stiffness and NVC abnormalities in the subgroup of RA patients not on cardiovascular medications. These findings are consistent with a role of impaired NO homeostasis in vascular injury in RA. Key Points • This study is the first to investigate the association between circulating ADMA levels and both micro- and macrovascular injury in rheumatoid arthritis using nailfold videocapillaroscopy and markers of arterial stiffness and subclinical atherosclerosis. • Significant correlations between ADMA, pulse wave velocity, and nailfold videocapillaroscopic abnormalities were observed in patients not receiving cardiovascular medications. • These findings suggest that impaired nitric oxide metabolism may contribute to peripheral microangiopathy and vascular dysfunction in rheumatoid arthritis.
MIDER Authors
Date
2025-11-22
Type
Article
Subject
ADMA, Arterial stiffness, Endothelial dysfunction, Nailfold videocapillaroscopy
Collections
Citation
Angeloudi E, Anyfanti P, Gavriilaki E, Pagkopoulou E, Spanou KV, Bekiari E, Doumas M, Dimitriadou V, Kitas GD, Dimitroulas T. Asymmetric dimethylarginine and vascular injury in rheumatoid arthritis, from capillaries to large vessels: results from a cross-sectional study. Clin Rheumatol. 2025 Nov 22. doi: 10.1007/s10067-025-07816-y
Journal / Source Title
Clinical Rheumatology
DOI
10.1007/s10067-025-07816-y
PMID
41275033
Publisher
Acta Medica Belgica
Publisher’s URL
https://link.springer.com/journal/10067