Differential Associations of Inflammatory and Endothelial Biomarkers with Disease Activity in Rheumatoid Arthritis of Short Duration (original) (raw)
Related papers
PubMed, 2008
Objective: Cardiovascular disease is a leading cause of mortality in rheumatoid arthritis (RA). Endothelial dysfunction often precedes manifest atherosclerosis. We assessed endothelial dysfunction and atherosclerosis in RA in context with laboratory markers. Methods: Fifty-two patients with RA and 40 matched healthy controls were studied. We assessed common carotid intima-media thickness (ccIMT) and flow- (FMD) and nitroglycerine-mediated vasodilation (NMD). We also assayed numerous immunological and metabolic laboratory markers. Results: FMD was significantly lower in RA (5.32% +/- 4.66%) compared to controls (8.30% +/- 3.96%) (p = 0.001). NMD was preserved in RA. ccIMT was significantly greater in patients with RA (0.63 +/- 0.14 mm) versus controls (0.54 +/- 0.15 mm) (p = 0.012). In patients with RA, ccIMT correlated with FMD% (R = -0.318, p = 0.022), age (R = 0.831, p < 0.001), and anti-dsDNA levels (R = 0.463, p = 0.006). FMD% correlated with serum interferon-gamma (IFN-gamma) levels (R = 0.516, p = 0.014). NMD% correlated inversely with the percentage of Th0 lymphocytes (R = -0.636, p = 0.006), serum immune complex (R = -0.692, p < 0.001), and IgM levels (R = -0.606, p = 0.003). Patients with RA were divided as "low" (< 0.65 mm) versus "high" (> 0.65 mm) ccIMT groups, and into "normal" (> 5%) versus "impaired" (< 5%) FMD% subsets. Low and high ccIMT groups differed significantly in age and serum interleukin 1 (IL-1) and anti-dsDNA levels. RA patients with normal versus impaired FMD% differed significantly in age, disease duration, and serum IFN-gamma levels. Lipoprotein(a) [Lp(a)] also correlated with rheumatoid factor (RF) and C-reactive protein (CRP); homocysteine (HCy) correlated with CRP and correlated inversely with folate and vitamin B12 production. Paraoxonase-1 (PON-1) activity correlated with serum tumor necrosis factor-alpha(TNF-alpha) and IL-6 levels. Conclusion: This was a well characterized RA population, where FMD and ccIMT were impaired, indicating early endothelial dysfunction and accelerated atherosclerosis, respectively. RA-related autoimmune-inflammatory mechanisms and metabolic factors including anti-CCP, RF, CRP, circulating immune complexes, IgM, TNF-alpha, IL-6, Th0/Th1 ratio, HCy, folate, vitamin B12, and PON-1 may all be involved in the development of vascular disease in RA. Although ccIMT and FMD, as well as some laboratory factors, have been assessed by other investigators in RA-associated atherosclerosis, our results regarding the possible involvement of anti-CCP, anti-dsDNA, Lp(a), some cytokines, and PON-1 activity are novel. Early determination of FMD% and ccIMT may be useful to assess RA patients with high cardiovascular risk.
Rheumatoid Arthritis (RA), is a inflammatory joint disease of chronic nature with predominant articular symptoms of pain ,swelling and stiffness.The most common extraarticular manifestation is cardiovascular disease which accounts for 50 % mortality in RA patients . Complex interplay between traditional CVD risk factors ,systemic inflammation and vascular function in RA are the reasons behind the scene worse outcome in RA patients .5 The MCC of mortality in Rheumatoid Arthritis patients is cardiovascular disease .1,2 Endothelial dysfunction is directly related to RA associated systemic inflammation The aim of the review is to discuss Endothelium ,its morphology and normal physiology ,consider endothelial dysfunction (ED ) in RA patients and relate endothelial dysfunction to systemic inflammation and traditional CVD risk factors and also consider the effect of drugs on vascular function.
Endothelial Function in Rheumatoid Arthritis
QJM : monthly journal of the Association of Physicians, 2018
Rheumatoid arthritis (RA) patients are at higher risk of accelerated atherosclerosis. We sought to assess endothelial dysfunction in RA to find a possible mechanistic pathway that will explain this clinical phenomenon. A prospective study recruited 44 RA patients with an active long standing (>12 months) disease. All underwent a detailed assessment of disease activity. To estimate the endothelial function the Brachial Artery Method was performed, measuring flow mediated diameter percent change (FMD%). Clustering analyses (hierarchical and k-means) were performed. Patients were compared to healthy subjects. 44 RA patients (54.42±11.14 years, females (72.7%)) with co-morbidities (70.5%), not taking TNF-blockers or DMARDs (63.6%). Only 6 (13.6%) had a normal endothelial function. Hierarchical and k-means clustering techniques showed statistically significant differences among the three clusters concerning DAS-28-ESR (p = 0.000), DAS-28-CRP (p = 0.001), CDAI (p = 0.002), SDAI (p = 0....
Clinical Rheumatology, 2008
Considerable evidence indicates that patients with rheumatoid arthritis (RA) are at greater risk of developing atherosclerosis and cardiovascular disease. Recent studies support the predictive ability of endothelial function measures for subsequent atherosclerotic events. We have investigated the effects of infliximab, a chimeric monoclonal anti-tumor necrosis factor (TNF) antibody, on endothelial vasodilation, measured by brachial ultrasonography and on the levels of inflammatory biomarkers and adhesion molecules in ten consecutive patients with severe long-standing RA, despite methotrexate therapy, during the loading phase of infliximab therapy. Flow-mediated dilation (FMD) in RA patients at baseline was significantly impaired compared with healthy controls (7.71 ± 2.78% vs 14.91 ± 6.41%; p = 0.008) and improved significantly after infliximab infusion (12.63 ± 1.63% vs 7.71 ± 2.78%; p = 0.005). At baseline, a statistically significant correlation between C-reactive protein levels and FMD was found (r = −0.69, p = 0.026). However, this improvement was transitory, as FMD values returned to baseline values before each infliximab infusion at weeks 2, 6 and 14. There were no significant differences in baseline brachial artery diameter between visits, although at each time, the diameter was increased. According to European League Against Rheumatism response criteria, all ten patients were good responders. No significant differences were observed in intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1, vascular endothelial growth factor and E-selectin plasma levels before and after each infusions. This study demonstrates that endothelial dysfunction is a reversible phenomenon in RA. The addition of anti-TNFα treatment reduces inflammatory symptoms in patients with severe RA. The improvement of endothelial function during the loading phase of therapy is transitory, suggesting an enhanced and persistent TNF-α generation within the arterial wall.
Indian Journal of Rheumatology, 2011
Background: Patients of rheumatoid arthritis (RA) have close association with an increased risk of cardiovascular disease. The earliest stage of atherosclerosis is exhibited by endothelial dysfunction, which is an expression of a systemic phenomenon. Objective: To evaluate the effect of inflammation of RA on endothelial function and its correlation with inflammatory markers, in young patients RA with low disease activity and without traditional cardiovascular risk factors by measuring endothelial reactivity. Methods: Flow-mediated vasodilatation (FMV), assessed by non-invasive ultrasound on the brachial artery, was evaluated in 50 young to middle aged patients with RA (age between 18 and 55 years) with disease activity score ≤ 3.2, without overt cardiovascular disease, at the age of 50 years, and sex matched healthy controls. Results: Mean FMV was found significantly lower in RA patients than in controls ([4.03 ± 1.9 vs. 8.7 ± 1.7] %; P < 0.001), and it was inversely related to C-reactive protein level (r = −0.415; P < 0.01) expressed at the value measured at the time of ultrasound evaluation. Conclusions: RA patients, young to middle aged, having low disease activity, free from overt cardiovascular disease and cardiovascular risk factors, have an altered endothelial reactivity that seemed to be primarily related to the inflammatory state of the disease.
Mediators of inflammation, 2018
To define the prevalence and determinants of peripheral microvascular endothelial dysfunction (ED) in a large series of rheumatoid arthritis (RA) patients free of previous cardiovascular events. Data from 874 RA patients enrolled in the EDRA study (Endothelial Dysfunction Evaluation for Coronary Heart Disease Risk Estimation in Rheumatoid Arthritis-ClinicalTrials.gov: NCT02341066) were analyzed. Log-transformed reactive hyperemia index (Ln-RHI) was evaluated by peripheral arterial tonometry (PAT) using the EndoPAT2000 device: values of Ln-RHI < 0.51 were considered indicative of peripheral ED. Peripheral microvascular ED was documented in one-third of RA patients (33.5%); in multiple logistic regression analysis, ACPA negativity and higher triglycerides concentrations were independently associated with the presence of peripheral ED [OR (95% CI) = 1.708 (1.218-2.396),< 0.01 and OR (95% CI) = 1.005 (1.002-1.009),< 0.01, respectively]. Multiple regression analysis showed a pos...
Endothelial dysfunction in young patients with rheumatoid arthritis and low disease activity
Annals of the Rheumatic Diseases, 2004
Background: Rheumatoid arthritis (RA) is associated with an increased risk of cardiovascular disease. Endothelial dysfunction represents the earliest stage of atherosclerosis. Objective: To evaluate the influence of chronic inflammatory state on endothelial function in patients with RA by measuring endothelial reactivity in young patients with RA with low disease activity and without traditional cardiovascular risk factors. Methods: Brachial flow mediated vasodilatation (FMV), assessed by non-invasive ultrasound, was evaluated in 32 young to middle aged patients with RA (age (59 years), with DAS28 (3.2 and without overt cardiovascular disease, and in 28 age and sex matched controls. Results: Mean (SD) FMV was significantly lower in patients than in controls (3.2 (1.3)% v 5.7 (2.0)%; p,0.001), inversely related to low density lipoprotein cholesterol (r = 20.45, p,0.05) and C reactive protein (CRP), expressed as the value at the moment of ultrasound evaluation (r = 20.44, p,0.05), as the average of CRP levels evaluated at different times during the disease (r = 20.47, p,0.05), or as the average of >4 determinations multiplied by the disease duration (r = 20.40, p,0.05). In a multivariate regression model, a lower brachial flow mediated vasodilatation was independently predicted by low density lipoprotein cholesterol (b = 20.40, p,0.05), average CRP levels multiplied by the disease duration (b = 20.44, p,0.05), and brachial artery diameter (b = 20.28, p,0.05). Conclusions: Young to middle aged patients with RA with low disease activity, free from cardiovascular risk factors and overt cardiovascular disease, have an altered endothelial reactivity that seems to be primarily related to the disease associated chronic inflammatory condition.
2002
Background-Rheumatoid arthritis (RA) is associated with accelerated atherosclerosis and increased cardiovascular morbidity and mortality. Striking similarities exist in the inflammatory and immunologic response in RA and atherosclerosis. Indeed, adhesion molecules and cytokines, tumor necrosis factor (TNF)-␣ in particular, are key mediators of joint inflammation and of vascular dysfunction and progression of atherosclerotic vascular disease. Hence, the aim of the present study was to assess the effect of chronic antiinflammatory treatment with the anti-TNF-␣ antibody infliximab on disease activity and endothelial function in patients with active RA. Methods and Results-Eleven RA patients (mean age 46Ϯ5 years; disease duration 9Ϯ2 years) with high disease activity despite treatment with stable doses of methotrexate (Յ25 mg/wk) and prednisone (Յ10 mg/d) were investigated. Clinical status and endothelium-dependent and-independent vasodilation of the brachial artery as assessed by high-resolution ultrasound were measured before and after 12 weeks of infliximab therapy. Flow-mediated vasodilation improved from 3.2Ϯ0.4% to 4.1Ϯ0.5% (Pϭ0.018), whereas endothelium-independent vasodilation with nitroglycerin and baseline diameter remained unchanged (13.6Ϯ1.2% versus 12.8Ϯ1.4%, Pϭ0.98, and 3.74Ϯ0.15 versus 3.66Ϯ0.11 mm, Pϭ0.54, respectively). Disease activity score (DAS28) was significantly reduced, from 5.6Ϯ0.3 to 3.5Ϯ0.6 (Pϭ0.002). Erythrocyte sedimentation rate and C-reactive protein were lowered from 34Ϯ7 to 19Ϯ5 mm/h (Pϭ0.04) and from 38Ϯ11 to 15Ϯ10 mg/L (Pϭ0.08), respectively. Conclusions-This is the first study to show that anti-TNF-␣ treatment improves endothelial function in RA. The data suggest that in RA, endothelial dysfunction is part of the disease process and is mediated by TNF-␣. (Circulation. 2002; 106:2184-2187.
Rheumatology, 2005
Vascular pathology, in the form of angiogenesis, is important in the perpetuation of rheumatoid arthritis (RA) and, in the form of endothelial dysfunction, contributes to associated cardiovascular co-morbidity. Emerging evidence suggests that TNFα blockade may modify vascular pathology in RA. Serum concentrations of vascular endothelial growth factor (VEGF), a potent endothelial cell-specific growth factor that is up-regulated by pro-inflammatory cytokines and by hypoxia, are elevated in RA and correlate with disease ...
A Multi Marker Evaluation of Cardiovascular Disease Risk in Patients with Rheumatoid Arthritis
IP Innovative Publication Pvt. Ltd, 2016
Background: Rheumatoid arthritis (RA), an inflammatory joint disease, is also associated with systemic effects. Patients with RA have an increased risk of morbidity and mortality that is mainly attributable to cardiovascular disease (CVD). Both traditional and novel risk factors are implicated in causing the increased CVD risk in RA patients. Materials and Method: Forty six RA patients, diagnosed with RA as per 1987 revised ARA criteria and forty six age and sex matched healthy controls were studied. Fasting lipid profile (Total cholesterol, triglycerides, HDL cholesterol), inflammatory markers (high sensitivity C reactive protein [hsCRP] and fibrinogen), oxidant and antioxidant markers (malondialdehyde [MDA] and ferric reducing ability of plasma [FRAP]), uric acid, homocysteine and Nitric oxide (NO) were measured in all subjects. Results: Among the traditional lipid parameters studied, triglycerides were increased in RA patients compared to controls (p=0.023). Both hsCRP (p<0.001) and fibrinogen (p=0.006) were elevated in RA patients than in controls. MDA levels were increased (p<0.001) and FRAP levels decreased (p<0.001) in patients with RA compared to controls. Uric acid and homocysteine levels showed no significant difference between RA patients and controls. Nitric oxide levels were increased in RA patients when compared with controls (p=0.030). Conclusion: Patients with rheumatoid arthritis were found to have an increased risk of CVD as evidenced by increased triglyceride levels, increased inflammatory markers, presence of oxidative stress. Hence, management of these patients should also include evaluation of CVD risk besides treatment of joint symptoms.