Asymmetric dimethylarginine and arterial stiffness in patients with rheumatoid arthritis: A case-control study (original) (raw)
Related papers
2015
Introduction. To compare the diagnostic values of laboratory variables, to present evaluations of the diagnostic test for asymmetric dimethyl arginine (ADMA), rheumatoid factor (RF), C-reactive protein (CRP), and DAS 28 index, and to define the effect of untreated rheumatoid arthritis on endothelial function. In order to determine whether ADMA changes depending on the disease evolution, ADMAwas used as an indicator for endothelial dysfunction.Methods. Using an ELISA technology of DLD-DiagnostikaGMBH for the detection of ADMA, the samples of serum and urine have been examined in 70 participants (35 RA who were not treated, 35 healthy controls). RF was defined with the test for agglutination (Latex RF test) in the same participants. Results. Out of 35 examined patients with RA, RF appeared in 17 patients (sensitivity of the test, 51.42%). In 20 of the 35 examined patients with RA, we found the presence of ADMA (sensitivity of the test, 57.14%). Anti-CCP antibody was present in 24 exam...
Clinical Rheumatology, 2019
Rheumatoid arthritis (RA) is the most common type of inflammatory arthritis leading to joint damage and physical disability. Cardiovascular diseases (CVDs) are considered a common comorbidity in patients with RA. However, the mechanism underlying its pathogenesis is not definitively explained. Endothelial dysfunction caused by impaired nitric oxide synthesis is an early indicator of cardiovascular disease. Asymmetric and symmetric dimethylarginine (ADMA and SDMA, respectively) the inhibitors of endothelial nitric oxide synthase (NOS) have emerged as novel CVD risk factor determiners. Concerning the unmet need to identify a salutary biomarker for CVD prediction, the purpose of this meta-analysis was to assess the serum/plasma ADMA and SDMA levels in RA patients compared with the healthy controls. A thorough literature search was performed in PubMed, Scopus, Web of Science, and Google Scholar to identify all studies reporting ADMA and/or SDMA levels in RA patients compared with healthy controls. The quality of studies was evaluated using the Newcastle-Ottawa scale (NOS). Pooled standard mean difference (SMD) with 95% confidence interval (CI) was used as the effect size in this study. We also conducted stratified analysis based on assay methods and median age of the participants. Fourteen articles were included. The pooled serum/plasma levels of ADMA were higher in RA patients compared with those of healthy controls (SMD = 1.02, 95% CI = 0.49 to 1.55); However, no statistical differences between RA patients and healthy controls in serum/plasma SDMA levels was seen (SMD = 0.57, 95% CI = −0.21 to 1.36). Subgroup analyses suggested that participants aged > 50 years had higher levels of ADMA rather than controls and the measurement method was a source of heterogeneity for ADMA. According to the results of this metaanalysis, ADMA measurement but not SDMA, can be useful for assessment of endothelial dysfunction as a predictor of CVD risk in RA patients. Prospero registration number: CRD42019121126.
Asymmetric Dimethyl Arginine as a Biomarker of Atherosclerosis in Rheumatoid Arthritis
Mediators of inflammation, 2018
Cardiovascular disease is the main cause of morbidity and mortality in rheumatoid arthritis (RA). Despite the advent on new drugs targeting the articular manifestations, the burden of cardiovascular disease is still an unmet need in the management of RA. The pathophysiology of accelerated atherosclerosis associated to RA is not yet fully understood, and reliable and specific markers of early cardiovascular involvement are still lacking. Asymmetric dimethylarginine is gaining attention for its implication in the pathogenesis of endothelial dysfunction and as biomarkers of subclinical atherosclerosis. Moreover, the metabolic pathway of methylarginines offers possible targets for therapeutic interventions to decrease the cardiovascular risk. The purpose of this review is to describe the main causes of increased methylarginine levels in RA, their implication in accelerated atherosclerosis, the possible role as biomarkers of cardiovascular risk, and finally the available data on current ...
Atherosclerosis, 2012
Background: Anti-Tumor Necrosis Factor (TNF)-a therapy improves vascular pathology in inflammatory arthropathies such as rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis. The L-arginine/ ADMA ratio is important for modulation of the nitric oxide synthase activity. We examined the effect of TNF-a antagonists on ADMA and L-arginine/ADMA, and associations between ADMA, L-arginine/ADMA, aortic stiffness and carotid intima media thickness (CIMT) in patients with inflammatory arthropathies. Methods: Forty-eight patients who started with anti-TNF-a therapy were compared with a non-treated group of 32 patients. Plasma ADMA and L-arginine were assessed at baseline, 3 and 12 months. In a subgroup of 55 patients, aortic pulse wave velocity (aPWV) was measured at baseline, 3 and 12 moths, and CIMT was examined at baseline and 12 months. Results: Anti-TNF-a therapy increased the L-arginine/ADMA ratio (mean [SD]) in the treatment group compared to the control group after 3 months (12 [29] vs. À13 [20], P < 0.001) and 12 months (7 [27] vs. À8 [19], P ¼ 0.008), but did not affect ADMA (3 months: 0.00 [0.09] mmol/L vs. 0.02 [0.07] mmol/L, P ¼ 0.42, 12 months: 0.01 [0.08] mmol/L vs. 0.01 [0.09] mmol/L, P ¼ 0.88). Baseline aPWV was associated
Mediators of Inflammation, 2012
Objectives. Impaired endothelial function represents the early stage of atherosclerosis, which is typically associated with systemic inflammatory diseases like rheumatoid arthritis (RA). As modulators of endothelial nitric oxide synthase expression, asymmetricdimethylarginine (ADMA) and apelin might be measured in the blood of RA patients to detect early atherosclerotic changes. We conducted a prospective, case-control study to investigate serum ADMA and apelin profiles of patients with early-stage RA (ERA) before and after disease-modifying antirheumatic drug (DMARD) therapy. Methods. We enrolled 20 consecutively diagnosed, treatment-naïve patients with ERA and 20 matched healthy controls. Serum ADMA and apelin levels and the 28-joint disease activity scores (DAS28) were assessed before and after 12 months of DMARDs treatment. All patients underwent ultrasonographic assessment for intima-media tickness (IMT) evaluation. Results. In the ERA group, ADMA serum levels were significantly higher than controls at baseline (P = 0.007) and significantly decreased after treatment (P = 0.012 versus controls). Baseline serum apelin levels were significantly decreased in this group (P = 0.0001 versus controls), but they were not significantly altered by treatment. IMT did not show significant changes. Conclusions. ERA is associated with alterations of serum ADMA and apelin levels, which might be used as biomarkers to detect early endothelial dysfunction in these patients.
The Journal of Rheumatology, 2011
Objective.Patients with rheumatoid arthritis (RA), a chronic inflammatory disease, have increased cardiovascular morbidity and mortality. We investigated whether early markers of RA inflammatory disease activity could predict later increased levels of pulse-wave velocity (PWV) and augmentation index (AIx), 2 measures of arterial stiffness.Methods.In total 238 patients with early RA were followed longitudinally and 108 were available for the 15-year followup examination. Comprehensive baseline clinical and radiographic data were collected in 1992. Arterial stiffness, measured as AIx and PWV (Sphygmocor apparatus), was recorded at the 15-year followup. Adjusted logistic univariate and multivariate analyses were performed with levels of AIx and PWV as the dependent variables, and variables reflecting baseline RA disease activity as possible predictors. The validity of the final models was examined in linear regression analyses.Results.Baseline C-reactive protein (CRP) above the median ...
Rheumatology, 2009
Objective. To quantify the relationship between arterial stiffness and cumulative inflammatory burden in patients with RA. Methods. We recruited RA patients without overt arterial disease aged 40-65 years, attending hospital rheumatology outpatient clinics. Standardized research nurse assessment included blood pressure (BP), pulse wave analysis (PWA, SphygmoCor), BMI, fasting blood sample (lipids, glucose, RF and ESR), patient questionnaire (smoking, alcohol, diet, exercise, family history of premature coronary heart disease and Stanford HAQ), current medication and medical record review. Cumulative inflammatory burden was measured as ESR areaunder-the-curve (ESR-years) extracted from medical records. Arterial stiffness was measured using PWA [aortic augmentation index (AIX@75)]. Multiple linear regression was used to adjust for age, sex and nine other cardiovascular risk factors. Results. We recruited 114 RA patients (mean age 54 years, female 81%, current DMARD 90%, current NSAID 70%, ACR criteria 56%) comprising 1040 RA person-years. Cholesterol, glucose and BMI were similar in women and men. Women had a longer duration of arthritis (10 vs 7 years) and were more likely to be seropositive (85 vs 71%). BP, smoking and alcohol consumption were lower for women. On fully adjusted analysis, an increase of 100 ESR-years was associated with an increase in AIX@75 of 0.51 (95% CI 0.13, 0.88). On fully adjusted analysis restricted to women the increase was 0.43 (95% CI 0.01, 0.85).
Association of non-invasive hemodynamics with arterial stiffness in rheumatoid arthritis
Scandinavian Cardiovascular Journal, 2018
Objectives. Arterial stiffness has emerged as a surrogate marker of cardiovascular disease. We investigated the role of myocardial performance and hemodynamic parameters in arterial stiffness in patients with rheumatoid arthritis (RA), which is accompanied by excess cardiovascular risk. Design. Arterial stiffness was evaluated with pulse wave velocity (PWV) in RA patients and controls. Cardiac and hemodynamic characterization was based on impedance cardiography. Cardiovascular risk factors, inflammatory markers and disease-related parameters were assessed. Results. PWV (8.2 ± 2.1 vs 7.4 ± 1.4 m/s, p ¼ .016) was higher among RA patients (n ¼ 104) compared to controls (n ¼ 52). In the RA group, PWV correlated with markers of cardiac contractibility (acceleration and velocity index), myocardial blood flow (cardiac output and stroke volume), preload (thoracic fluid content) and afterload (systemic vascular resistance) (p < .05 for all). PWV tended to increase with decreasing oxygen delivery to the myocardium (r ¼ 0.055), as well as with shortening of the ejection duration of the left ventricle (p ¼ .058). However, these associations no longer remained significant after adjustment for classical cardiovascular risk factors, inflammation and corticosteroid use, which were independently associated with PWV. Conclusions. Among patients with RA, arterial stiffness appears as the composite of cardiovascular risk factors and inflammation, while corticosteroid use emerges as an additional adverse factor.