Subclinical Atherosclerosis in Patients with Rheumatoid Arthritis and Low Cardiovascular Risk: The Role of von Willebrand Factor Activity

Abstract

BackgroundTo evaluate association between von Willebrand factor (vWF) activity, inflammation markers, disease activity, and subclinical atherosclerosis in patients with rheumatoid arthritis (RA) and low cardiovascular risk.MethodsAbove mentioned parameters were determined in blood samples of 74 non-diabetic, normotensive, female subjects, with no dyslipidemia(42 patients, 32 matched healthy controls, age 45.3±10.0 vs. 45.2±9.8 years). Intima-media thickness (IMT) was measured bilaterally, at common carotid, bifurcation, and internal carotid arteries. Subclinical atherosclerosis was defined as IMT>IMTmean+2SD in controlsat each carotid level and atherosclerotic plaque as IMT>1.5 mm. Majority of RA patients were on methotrexate (83.3%), none on steroids >10 mg/day or biologic drugs. All findings were analysed in the entire study population and in RA group separately.ResultsRA patients with subclinical atherosclerosis had higher vWF activity than those without (133.5±69.3% vs. 95.3±36.8%, p<0.05). Predictive value of vWF activity for subclinical atherosclerosis was confirmed by logistic regression. vWF activity correlated significantly with erythrocyte sedimentation rate, fibrinogen, modified disease activity scores (mDAS28–ESR, mDAS28–CRP), modified Health Assessment Questionnaire (p<0.01 for all), duration of smoking, number of cigarettes/day, rheumatoid factor concentration (p<0.05 for all), and anti-CCP antibodies (p<0.01). In the entire study population, vWF activity was higher in participants with subclinical atherosclerosis (130±68% vs. 97±38%, p<0.05) or atherosclerotic plaques (123±57% vs. 99±45%, p<0.05) than in those without. Duration of smoking was significantly associated with vWF activity (β 0.026, p = 0.039).ConclusionsWe demonstrated association of vWF activity and subclinical atherosclerosis in low-risk RA patients as well as its correlation with inflammation markers, all parameters of disease activity, and seropositivity. Therefore, vWF might be a valuable marker of early atherosclerosis in RA patients.

Causes of changes in carotid intima-media thickness: a literature review

“…Recent quantities clinical observations have confirmed that RA is associated with increased CIMT [ 96 - 99 ]. The mechanisms of RA-related CIM thickening included increased levels of Ox-LDL) [ 100 , 101 ], vWF activity [ 102 ], serum mannose-binding lectin [ 103 ], and PWV [ 104 ] as well as increased levels of inflammation markers [ 99 , 102 ] such as IL-17 [ 105 ], and CRP [ 106 ] and lower levels of β-carotene [ 101 ], vitamin D, CD34+ cells [ 100 , 104 ] and NO [ 101 ]. Psoriasis is associated with increased mean CIMT [ 107 ] and may increase the burden of subclinical atherosclerosis [ 107 , 106 ].…”

“…More severe subclinical atherosclerosis was observed in patients with PsA [ 108 ] compared with patients with cutaneous psoriasis without arthritis (PsC). The causes of atherosclerosis in PsA include markers of accelerated atherosclerosis such as ox-LDLs and NO [ 101 ] as well as endothelial dysfunction [ 106 ], PsA disease duration, more severe skin disease and increased inflammatory markers; however, atherosclerosis in PsA was not associated with traditional CV risk factors [ 108 ]. Furthermore, increased CIMT was associated with juvenile idiopathic arthritis [ 109 ], systemic lupus erythematosus [ 110 ], and BD [ 111 ].…”

Spectral Doppler and automated software-guided ultrasound assessment of bilateral common carotid intima-media thickness in spondyloarthritis: is there a correlation with clinical findings?

“… 38 – 42 Common carotid artery IMT shows positive correlations with the duration of inflammatory articular disease, laboratory parameters reflecting inflammation, age, and traditional risk factors for cardiovascular disease. 43 – 46 Cardiology societies suggest that evaluation of common carotid artery IMT should form part of the medical assessment of patients at increased cardiovascular risk, 40 and rheumatology guidelines recommend that patients with inflammatory arthritis should undergo ultrasound evaluation of the carotid arteries. 47 Evaluation of these criteria in arthritis was established based on histologic evidence.…”

Evaluation of the Risk of Getting Peripheral Artery Disease in Rheumatoid Arthritis and the Selection of Appropriate Diagnostic Methods

“…Anti-inflammatory medications do not eradicate irreversible changes, but decrease further arterial stiffness progression. Rheumatoid Factor positivity is associated with more morphological changes in the vasculature [ 20 , 32 ]. A study headed by Laura Geraldino-Pardilla used F-Fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG-PET/CT) to detect ascending aorta inflammation [ 7 ].…”