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Oxidative Stress Biomarkers and Peripheral Endothelial Dysfunction in Rheumatoid Arthritis: A Monocentric Cross-Sectional Case-Control Study.

ABSTRACT: Previous studies have suggested that oxidative stress may heighten atherosclerotic burden in rheumatoid arthritis (RA), but direct evidence is lacking. OBJECTIVE:To evaluate the relationship between established plasma oxidative stress biomarkers and peripheral endothelial dysfunction (ED), a marker of early atherosclerosis, in RA. METHODS:Paroxonase-1 (PON-1), protein-SH (PSH), and malondialdehyde (MDA) were measured in 164 RA patient s and 100 age- and sex-matched healthy controls without previous cardiovascular events. Peripheral ED, evaluated by flow-mediated pulse amplitude tonometry, was defined by log-transformed reactive hyperemia index (Ln-RHI) values < 0.51. RESULTS:PON-1 activity and PSH concentrations were significantly reduced in RA patients compared to controls. In regression analysis, increased plasma MDA levels were significantly associated with reduced Ln-RHI [B coefficient (95% CI) = -0.003 (-0.005 to -0.0008), p = 0.008] and the presence of peripheral ED (OR (95% CI) = 1.75 (1.06-2.88), p = 0.028). Contrary to our expectations, increased PON-1 activity was significantly associated, albeit weakly, with the presence of ED (OR (95% CI) = 1.00 (1.00-1.01), p = 0.017). CONCLUSIONS:In this first evidence of a link between oxidative stress and markers of atherosclerosis, MDA and PON-1 showed opposite associations with peripheral vasodilatory capacity and the presence of ED in RA. Further studies are needed to determine whether this association predicts atherosclerotic events in the RA population.

SUBMITTER: Bassu S

PROVIDER: S-EPMC7504109 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Oxidative Stress Biomarkers and Peripheral Endothelial Dysfunction in Rheumatoid Arthritis: A Monocentric Cross-Sectional Case-Control Study.

Bassu Stefania S Zinellu Angelo A Sotgia Salvatore S Mangoni Arduino Aleksander AA Floris Alberto A Farina Giuseppina G Passiu Giuseppe G Carru Ciriaco C Erre Gian Luca GL

Molecules (Basel, Switzerland) 20200825 17

Previous studies have suggested that oxidative stress may heighten atherosclerotic burden in rheumatoid arthritis (RA), but direct evidence is lacking.<h4>Objective</h4>To evaluate the relationship between established plasma oxidative stress biomarkers and peripheral endothelial dysfunction (ED), a marker of early atherosclerosis, in RA.<h4>Methods</h4>Paroxonase-1 (PON-1), protein-SH (PSH), and malondialdehyde (MDA) were measured in 164 RA patient s and 100 age- and sex-matched healthy controls ...[more]

PMID: 32854225

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Project description:BackgroundArsenic (As) exposure has been associated with increased risk for cardiovascular disease (CVD) and with biomarkers of potential CVD risk and inflammatory processes. However, few studies have evaluated the effects of As on such biomarkers in U.S. populations, which are typically exposed to low to moderate As concentrations.ObjectivesWe investigated associations between As exposures and biomarkers relevant to inflammation, oxidative stress, and CVD risk in a subset of participants from the New Hampshire Health Study, a population with low to moderate As exposure (n=418).MethodsAssociations between toenail As, total urine As (uAs), and %uAs metabolites [monomethyl (%uMMAV), dimethyl (%uDMAV), and inorganic (%iAs) species] and plasma biomarkers, including soluble plasma vascular and cellular adhesion molecules (VCAM-1 and ICAM-1, respectively), matrix metalloproteinase-9 (MMP-9), tumor necrosis factor-α, plasminogen activator inhibitor-1 (PAI-1), and urinary oxidative stress marker 15-F2t-isoprostane (15-F2t-IsoP), were evaluated using linear regression models.ResultsCovariate-adjusted estimates of associations with a doubling of urinary As suggested an 8.8% increase in 15-F2t-IsoP (95% CI: 3.2, 14.7), and a doubling of toenail As was associated with a 1.7% increase in VCAM-1 (95% CI: 0.2, 3.2). Additionally, a 5% increase in %uMMA was associated with a 7.9% increase in 15-F2t-IsoP (95% CI: 2.1, 14.1), and a 5% increase in %uDMA was associated with a 2.98% decrease in 15-F2t-IsoP [(95% CI: -6.1, 0.21); p=0.07]. However, in contrast with expectations, a doubling of toenail As was associated with a 2.3% decrease (95% CI: -4.3, -0.3) in MMP-9, and a 5% increase in %uMMA was associated with a 7.7% decrease (95% CI: -12.6, -2.5) in PAI-1.ConclusionIn a cross-sectional study of U.S. adults, we observed some positive associations of uAs and toenail As concentrations with biomarkers potentially relevant to CVD pathogenesis and inflammation, and evidence of a higher capacity to metabolize inorganic As was negatively associated with a marker of oxidative stress. https://doi.org/10.1289/EHP2062.

Project description:IntroductionLimited data are available to explain nonadherence to methotrexate (MTX) therapy in patients with rheumatoid arthritis (RA). Better understanding of patterns of MTX use and reasons for nonadherence may help identify patients who would benefit from alternative RA treatments and potentially aid in developing strategies to increase overall adherence. The purpose of this study was to assess patients' self-reported adherence to MTX and to identify reasons for nonadherence.MethodsPatient panel members in the US self-reporting a diagnosis of RA of ?3 months' and current MTX use of ?4 weeks' duration, with or without concomitant use of another RA prescription medication, participated in this cross-sectional, web-based survey.ResultsThe sample population (251 MTX monotherapy, 250 MTX combination therapy) was predominantly female, white, non-Hispanic, and educated; 48% were 18-44 years-old, 47% had medical comorbidities, 66% were first diagnosed with RA ?5 years earlier, 51% reported MTX use of <1 year, and 83% reported oral MTX use. Forty-two percent reported not taking MTX exactly as prescribed. Reasons for nonadherence included forgetting to take it (33%), not needing it when feeling well (24%), and concern about long-term safety (24%). Among nonadherent patients, 53% took smaller doses, 52% skipped doses, and 6% reported other nonprescribed ways of taking MTX. Younger age, male sex, and shorter duration of MTX use were associated with poorer self-reported adherence. Compared with monotherapy patients, combination therapy patients, particularly those taking ?2 other RA prescriptions, were less likely to report high adherence.ConclusionNearly half the sample reported poor MTX adherence because they forgot to take it, thought it was not needed when they felt well, or had long-term safety concerns. Patients taking ?2 other RA prescription medications were less likely to report good adherence. Reducing treatment burden without sacrificing efficacy may be a strategy worth evaluating.

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Project description:Cutaneous manifestations are fairly common in rheumatoid arthritis (RA) and they can help in early diagnosis, prompt treatment, and hence reduced morbidity from the disease.The objective of the present study was to find out the different patterns of dermatoses in a group of patients with RA from Eastern India.Consecutive patients fulfilling the American Rheumatism Association 1987 revised criteria for the classification of RA and who had different dermatoses were included in this cross-sectional study done over a period of 8 years in a tertiary care hospital in Eastern India. Thorough clinical examination and appropriate laboratory investigations were performed as needed. Data were recorded in a predesigned schedule, and appropriate statistical analysis was done.We studied 111 evaluable patients with an age range of 19-71 years and a female to male ratio of 7:1. The mean disease duration of RA was 6.5 years. Cutaneous infections as a group was the most common mucocutaneous manifestation (34.2%) followed by xerosis including ichthyotic skin changes (27%), pigmented purpuric dermatoses (14.4%), leg ulcer (9.9%), periungual telangiectasia (9.9%), rheumatoid nodules (RNs) (8.1%), purpura and ecchymoses (7.2%), small vessel vasculitis in (7.2%), corn and callosities (6.3%), palmar erythema (4.5%), and neutrophilic dermatosis (4.5%). Raynaud's phenomenon was found in 3.6% patients and panniculitis in (3.6%) patients. Rheumatoid factor (RF) and anti-cyclic citrullinated peptides antibody were positive in 74.8% and 88.3% patients, respectively. No statistically significant difference of incidence of leg ulcer, small vessel vasculitis, RN, or Raynaud's phenomenon could be noted between RF positive and negative groups.Being an institution-based study, the study findings may not reflect the true situation in the community which remained a limitation of this study.While some of the features of this study were analogous to Western data, other features showed discordance which may be due to ethnic variations among the patients with RA.

Dataset Information

Oxidative Stress Biomarkers and Peripheral Endothelial Dysfunction in Rheumatoid Arthritis: A Monocentric Cross-Sectional Case-Control Study.

Publications

Oxidative Stress Biomarkers and Peripheral Endothelial Dysfunction in Rheumatoid Arthritis: A Monocentric Cross-Sectional Case-Control Study.

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