scholarly journals Changes of Metabolic Biomarker Levels upon One-Year Anti-TNF-α Therapy in Rheumatoid Arthritis and Ankylosing Spondylitis: Associations with Vascular Pathophysiology

Biomolecules ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1535
Author(s):  
Monika Czókolyová ◽  
Anita Pusztai ◽  
Edit Végh ◽  
Ágnes Horváth ◽  
Anita Szentpéteri ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Ankylosing Spondylitis ◽  
Disease Activity ◽  
Vascular Function ◽  
Certolizumab Pegol ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Metabolic Parameters ◽  
Clinical Markers ◽  
One Year

Background: Cardiovascular (CV) morbidity, mortality, and metabolic syndrome are associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Here, lipids and other metabolic markers in relation to vascular function and clinical markers were evaluated in RA and AS patients undergoing one-year anti-TNF therapy. Patients and methods: Fifty-three patients including 36 RA patients treated with either etanercept (ETN) or certolizumab pegol (CZP) and 17 AS patients treated with ETN were included in a 12-month follow-up study. Various lipids, paraoxonase (PON) and arylesterase (ARE) activities, myeloperoxidase (MPO) and adipokine levels were determined overtime. Ultrasonography was performed to determine flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT), and arterial pulse-wave velocity (PWV) in all patients. All assessments were performed at baseline and 6 and 12 months after treatment initiation. Results: Anti-TNF therapy decreased ARE activity, MPO, adiponectin, and chemerin levels after 12 months (p < 0.05). Lipids, PON activity, and leptin remained unchanged. Regression analyses suggested variable associations of IMT, PWV, and FMD with ARE, MPO, leptin, and lipids (p < 0.05). On the other hand, these metabolic parameters were significantly associated with disease duration, CV history, CRP, obesity, PWV, and IMT (p < 0.05). One-year anti-TNF treatment together with baseline leptin (p = 0.039) or CRP (p = 0.016) levels determined 12 months of lipid changes overtime. TNF inhibition together with baseline disease activity determined ARE activity changes (p = 0.046). Anti-TNF therapy and baseline chemerin levels determined IMT changes overtime (p = 0.003). Conclusions: Assessment of various metabolic parameters together with disease activity, CRP, and ultrasound-based techniques may exert additional value in determining CV burden and in monitoring the effects of biologics on preclinical vascular pathophysiology.

scholarly journals Effects of 1-year anti-TNF-α therapy on vascular function in rheumatoid arthritis and ankylosing spondylitis

2019 ◽  
Vol 40 (3) ◽  
pp. 427-436 ◽  
Author(s):  
Edit Végh ◽  
György Kerekes ◽  
Anita Pusztai ◽  
Attila Hamar ◽  
Szilvia Szamosi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Ankylosing Spondylitis ◽  
Vascular Function ◽  
Certolizumab Pegol ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Cardiovascular Morbidity And Mortality ◽  
Tnf Α ◽  
Flow Mediated Vasodilation

AbstractAccelerated atherosclerosis, increased cardiovascular morbidity and mortality have been associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Vascular function, clinical and laboratory markers and the effects of anti-TNF therapy were assessed in arthritides. Fifty-three 53 patients including 36 RA patients treated with either etanercept (ETN) or certolizumab pegol and 17 AS patients treated with ETN were included in a 12-month follow-up study. Ultrasonography was performed to determine flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT) and arterial pulse-wave velocity (PWV) in all patients. All assessments were performed at baseline and 6 and 12 months after treatment initiation. A significant improvement of brachial artery FMD was observed after 6 months (p = 0.004). A tendency of FMD improvement was also observed after 12 months (p = 0.065). ccIMT did not change throughout the year. PWV significantly improved after 12 months (p = 0.034). Higher baseline ccIMT (p = 0.009) and PWV (p = 0.038) were associated with clinical non-response (cNR) versus response (cR) to biologics. Multiple analysis confirmed the association of baseline ccIMT with age (p = 0.003) and cNR (p = 0.009), as well as that of baseline PWV with age at diagnosis (p = 0.022) and current chest pain (p = 0.004). Treatment itself determined the 12-month changes in FMD (p = 0.020) and PWV (p = 0.007). In a mixed cohort of RA and AS patients, TNF inhibition improved or stabilized vascular pathophysiology. Inflammation may be associated with FMD, while, among others, cNR may influence vascular function.

Soluble vascular biomarkers in rheumatoid arthritis and ankylosing spondylitis: effects of one-year anti-TNF-α therapy

2020 ◽  
pp. jrheum.200916
Author(s):  
Anita Pusztai ◽  
Attila Hamar ◽  
Ágnes Horváth ◽  
Katalin Gulyás ◽  
Edit Végh ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Ankylosing Spondylitis ◽  
Oxidized Ldl ◽  
Certolizumab Pegol ◽  
Intima Media Thickness ◽  
Serum Levels ◽  
Urokinase Plasminogen Activator Receptor ◽  
Tnf Α ◽  
One Year ◽  
Vascular Biomarkers

Objective Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) have been associated with cardiovascular (CV) disease. The treatment of arthritis by tumour necrosis factor α (TNF- α) inhibitors may decrease the serum concentrations of vascular biomarkers. We determined circulating levels of oxidized LDL (oxLDL)/β2 glycoprotein I (β2GPI) complexes, antibodies to 60 kDa heat shock protein (anti-Hsp60), soluble urokinase plasminogen activator receptor (suPAR) and Brain type natriuretic peptide (BNP) fragment in sera of RA and AS patients undergoing anti-TNF treatment. Methods Fifty-three RA/AS patients were treated with etanercept (ETN) or certolizumab pegol (CZP) for one year. Circulating oxLDL/β2GPI complex (AtherOx®), anti- Hsp60 IgG and BNP8-29 fragment levels were assessed by ELISA. suPAR levels were determined by suPARnostic® Quick Triage test. Flow-mediated vasodilation (FMD), carotid intima-media thickness (IMT) and arterial pulse-wave velocity (PWV) were determined by ultrasound. Results One-year anti-TNF treatment significantly decreased oxLDL/β2GPI levels, as well as suPAR levels in patients with “critically” high suPAR levels at baseline. In RA, BNP levels were higher in seropositive vs seronegative patients. Serum levels of these vascular biomarkers variably correlated with lipids, ACPA, RF and CRP. IMT positively correlated with BNP, PWV with suPAR and anti-Hsp60, while FMD inversely associated with anti-Hsp60. In RM-ANOVA analysis, disease activity supported the effects of anti-TNF treatment on 12-month changes in oxLDL/β2GPI. IMT supported the effects of therapy on changes of anti-Hsp60 and suPAR. Conclusion These biomarkers may be involved in the pathogenesis of atherosclerosis underlying RA/AS. TNF inhibition variably affect the serum levels of oxLDL/β2GPI, suPAR and BNP.

scholarly journals Associations of vascular and bone status in arthritis patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anita Pusztai ◽  
Attila Hamar ◽  
Monika Czókolyová ◽  
Katalin Gulyás ◽  
Ágnes Horváth ◽  
...  
Keyword(s):  
Disease Activity ◽  
Certolizumab Pegol ◽  
Cathepsin K ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Quantitative Ct ◽  
Bone Status ◽  
Vascular Markers ◽  
One Year ◽  
Vascular Biomarkers

AbstractCardiovascular (CV) disease and osteoporosis (OP) have been associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Bone and vascular biomarkers and parameters along with the effect of 1-year anti-TNF therapy on these markers were assessed in order to determine correlations between vascular pathophysiology and bone metabolism in RA and AS. Thirty-six patients treated with etanercept or certolizumab pegol and 17 AS patients treated with ETN were included in a 12-month follow-up study. Bone and vascular markers were previously assessed by ELISA. Bone density was measured by DXA and quantitative CT (QCT). Flow-mediated vasodilation (FMD), common carotid intima-media thickness (IMT) and pulse-wave velocity (PWV) were assessed by ultrasound. Multiple correlation analyses indicated associations between bone and vascular markers. Osteoprotegerin, sclerostin and cathepsin K were significantly associated with FMD, IMT and PWV, respectively (p < 0.05). Moreover, total and trabecular BMD determined by QCT inversely correlated with IMT (p < 0.05). On the other hand, among vascular parameters, platelet-derived growth factor BB and IMT correlated with DXA femoral and QCT total BMD, respectively (p < 0.05). In the RM-ANOVA analysis, anti-TNF treatment together with baseline osteocalcin, procollagen 1 N-terminal propeptide (P1NP) or vitamin D3 levels determined one-year changes in IMT (p < 0.05). In the MANOVA analysis, baseline disease activity indices (DAS28, BASDAI), the one-year changes in these indices, as well as CRP exerted effects on multiple correlations between bone and vascular markers (p < 0.05). As the pattern of interactions between bone and vascular biomarkers differed between baseline and after 12 months, anti-TNF therapy influenced these associations. We found a great number of correlations in our RA and AS patients undergoing anti-TNF therapy. Some of the bone markers have been associated with vascular pathophysiology, while some vascular markers correlated with bone status. In arthritis, systemic inflammation and disease activity may drive both vascular and bone disease.

scholarly journals AB0234 ASSOCIATION OF HOMOCYSTEINE LEVEL AND CAROTID INTIMA-MEDIA THICKNESS IN PATIENTS WITH RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1417.3-1417
Author(s):  
D. Anghel ◽  
L. Otlocan ◽  
R. Bursuc ◽  
E. Busuioc ◽  
A. Manolache ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Homocysteine Level ◽  
Intima Media Thickness ◽  
Antiplatelet Agents ◽  
Carotid Intima Media Thickness ◽  
Tnf Alpha ◽  
Das28 Score ◽  
Media Thickness ◽  
Alpha Therapy

Background:Homocysteine (Hcy) has been implicated in atherogenesis. High homocysteine level can predict cardiovascular events, including death. Atherosclerosis has a high incidence in patients with Rheumatoid Arthritis (RA).Objectives:The aim of this study is to evaluate the relationship between serum homocysteine levels and carotid atherosclerosis in patients with RA and anti-TNF therapy.Methods:Our study included 80 RA patients divided into two groups: 45 patients were with anti-TNF-alpha therapy (Adalimumab, Infliximab, Etanercept) and 35 RA patients with disease-modifying antirheumatic drugs (DMARDs). The patients were diagnosed with RA used ACR/EULAR 2010 Classification Criteria. We measured carotid intima-media thickness (CIMT) using high-resolution Doppler ultrasonography at baseline and then at 12 months. CIMT above 0.9 mm is an atherosclerosis marker. We considered high levels of homocysteine in the serum above 15 µmol/L. All patients had treatment with hypolipemiant drugs and antiplatelet agents during the 12 months. Other parameters were analyzed at baseline and after 12 months: age, lipid profile (HDL, LDL, and cholesterol), ESR and disease activity score (DAS28<2.6 means remission; DAS28=2.6-3.2 means low disease activity, DAS28=3.2-5.1 means moderate disease activity; DAS28>5.1 high disease activity).Results:45 patients received anti-TNF-alpha therapy (mean age 45.50±9.69 years) and 35 RA patients had treatment with DMARDs (mean age 48.3±8.9 years). High Hcy levels were found on 34% patients in DMARDs group and 21% patients in anti-TNF group. After 12 months of treatment, patients with high levels of Hcy and anti-TNF therapy had a significant decrease in CIMT. In patients with low Hcy level the decrease in CIMT was insignificantly statistic. In DMARDs group atherosclerotic plaque was detected to 26 patients (74.29%) and 21 (46.66%) patients were detected into anti-TNF group. After 12 months CIMT was significantly higher in DMARDs group and the difference was statistically significant compared to baseline and to anti-TNF group (p=0.0002). High DAS28 score was associated with increased CIMT and hyperhomocysteinemia in both groups (p=0.0001).Conclusion:Increased Hcy levels were associated with increased CIMT values in both groups. In RA patients with anti-TNF therapy and high Hcy levels, reduction of CIMT was statistically higher than in patients with DMARDs treatment.Disclosure of Interests:None declared

scholarly journals Factors affecting carotid intimal medial thickness in patients with rheumatoid arthritis, an analytical cross-sectional study

2019 ◽  
Vol 6 (3) ◽  
pp. 628
Author(s):  
K. M. Prabhuswamy ◽  
M. Virgin Joena
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Cross Sectional Study ◽  
Healthy Controls ◽  
Sectional Study ◽  
Cross Sectional ◽  
Media Thickness ◽  
The Mean

Background: IMT assessment as a non-invasive imaging test is quite widely used especially among RA patients, the clinical applications of using such knowledge is scarce, hence study was conducted to compare the carotid artery intima-media thickness (CIMT) in patients with rheumatoid arthritis (RA) with healthy controls also to study the correlation between duration of rheumatoid arthritis, the activity of rheumatoid arthritis and other factors influencing (CIMT).Methods: In analytical cross-sectional study, of 80 participants of RA and 40 healthy controls, “DAS28” was used to assess disease activity.  Carotid intima-media thickness assessed using carotid ultrasonography.Results: Mean age of the cases and controls was 43.9 and 44.38 years. Subjects with duration of disease <2 years, to 5 years and >5 years were 35%, 45% and 20%. The mean carotid intima-media thickness was 5.61mm in controls, and CIMT was 6.11mm in people below 2 years and 7.08 mm in people between 2 to 5 years and 8.00mm in people above 5 years which was statistically significant. The mean carotid intima-media thickness was 5.61mm controls and 6.86mm in people with low, 7.00mm in people with moderate and 6.95mm in people with high disease activity, which was statistically significant.Conclusions: Study findings revealed risk of increase in carotid intima-media thickness higher among RA patients in the later stages and can increase the patients’ susceptibility to cardiovascular events. The factors showing strong association with intimal medial thickness were the age and symptoms duration.

scholarly journals Correlation Between Carotid Intima-Media Thickness and the Activity of Rheumatoid Arthritis: A 1-Year Cross-Sectional Study

2018 ◽  
Vol 30 (3) ◽  
pp. 34-41
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Tender Joint Count ◽  
Tender Joint ◽  
Media Thickness ◽  
Das 28 ◽  
Significant Difference ◽  
The Mean

Background and objectives: Among several noninvasive techniques available, a high-resolution B-mode ultrasonography is the widely used technique to measure carotid intima-media thickness (CIMT) in rheumatoid arthritis (RA) patients with elevated cardiovascular risk. The present study was undertaken to explore the clinical relationship between CIMT and disease activity in patients with RA. Methods: This study involved 50 adult patients with RA. Demographic, physical, systemic, and clinical data and history of the patients were recorded. Investigations, such as erythrocyte sedimentation rate, highly sensitive C-reactive protein, renal and liver function tests, RA factor, and anticyclic citrullinated peptide antibody tests were performed. CIMT was assessed using highresolution B-mode ultrasonography and the disease severity was assessed based on disease activity score (DAS) 28. Results: The mean age of the RA patients was 49.88 ± 12.12 years with male predilection. The mean duration, mean European League Against Rheumatism (EULAR) criteria score, and mean DAS 28 score in RA patients were 3.62 ± 3.25 years, 8.10 ± 1.58, and 4.91 ± 1.11, respectively. The mean CIMT observed in RA patients was 0.94 ± 0.31 cm. Significant difference was observed in the mean CIMT values of different variables, including duration of joint pain (P = 0.007), tender joint count (P < 0.001), swollen joint count (P < 0.001), EULAR criteria score (P < 0.001), and DAS 28 score (P < 0.001). Also, CIMT correlated positively with tender joint count (r = 0.711; P < 0.001), swollen joint count (r = 0.673; P < 0.001), EULAR criteria score (r = 0.611; P < 0.001), and DAS 28 score (r = 0.729; P < 0.001). Conclusion: A strong correlation was observed between CIMT and disease activity in patients with RA. Hence, CIMT can be a useful surrogate marker for detecting atherosclerosis in patients with RA.

scholarly journals Gender Differences in Cardiovascular Risk Profile in Rheumatoid Arthritis Patients with Low Disease Activity

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Bożena Targońska-Stępniak ◽  
Małgorzata Biskup ◽  
Wojciech Biskup ◽  
Maria Majdan
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Hdl Cholesterol ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Risk Profile ◽  
Atherogenic Index ◽  
Low Disease Activity ◽  
Amino Terminal ◽  
Cv Disease

Objective. Patients with rheumatoid arthritis (RA) have an excess risk of cardiovascular (CV) disease (CVD). The objective of the study was to compare CV risk profile in female and male RA patients with low disease activity. Materials and Methods. The study group consisted of 70 RA patients with continuous low disease activity and no CVD (54 women, 16 men) and 33 healthy controls of comparable age. The groups were assessed for blood pressure, serum amino-terminal pro-brain natriuretic peptide (NT-proBNP), carotid intima media thickness (cIMT), electrocardiography, ejection fraction (EF), and diastolic dysfunction (DD). Results. Significantly higher burden of atherosclerosis, as revealed by higher cIMT, was found in males [0.93 (0.2) mm] vs females [0.80 (0.2) mm]. The risk of 10-year CVD was significantly higher in men than in women with RA. High/very high risk of fatal CVD was found in 62.5% of male patients. Males were significantly more often current/ex-smokers and had lower HDL-cholesterol and higher atherogenic index. There were no significant differences in NT-proBNP, QTc duration, and parameters of EF and DD. Conclusions. In RA patients with continued low disease activity, a higher burden of atherosclerosis was found in males than in females. The data suggest a significant impact of traditional CV risk factors.

Evaluation of serum endothelial cell-specific molecule-1 levels and carotid intima-media thickness in patients with ankylosing spondylitis / Ankilozan spodilitli hastalarda serum endothelial cell-specific molecule-1 ve karotis intima media kalınlığının değerlendirilmesi

2016 ◽  
Vol 41 (1) ◽  
Author(s):  
Hakan Türkön ◽  
Ferhat Gökmen ◽  
Sema Uysal ◽  
Ayla Akbal ◽  
Beşir Şahin İnceer ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Ankylosing Spondylitis ◽  
Disease Activity ◽  
Activity Index ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Chronic Inflammatory Disease ◽  
Control Group ◽  
Media Thickness ◽  
Significant Difference

AbstractObjective: Ankylosing spondylitis (AS) is a chronic inflammatory disease and the increased mortality in these patients is largely caused by cardiovascular diseases. Endothelial cell-specific molecule-1 (ESM-1) is a novel marker to assess endothelial dysfunction and expressed by the vascular endothelium. In this study, the serum ESM-1 levels in patients with AS and the possible association between serum ESM-1 and carotid intima-media thickness (CIMT) as a marker of atherosclerosis was evaluated.Methods: A total of thirty-seven patients with AS and thirty healthy control subjects were included in this study. ESM-1, erythrocyte sedimentation rate(ESR),C-reactive protein (CRP) and CIMT were measured in all subjects. ESM-1 levels were measured by ELISA method. The disease activity of patients with AS were assessed using questionnaires Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI).Results: Serum ESM-1 levels were lower in AS patients than in healthy controls. However, there was no statistically significant difference between ESM-1 levels (304.3±185.2 vs. 373.9±206.9 ng/L, respectively; p=0.064). Patients with AS had significantly higher CIMT levels compared with controls (0.77±0.16 vs. 0.53±0.09 mm, respectively; p<0.001). While a statistically significant positive correlation was detected in all subjects between CIMT levels and ESR, CRP (r=0.378, p=0.002, r=0.547, p<0.001, respectively), no significant correlation was detected between serum ESM-1 levels and ESR, CRP, BASDAI, BASFI and CIMT.Conclusion: The results showed that CIMT values in AS patients were increased when compared to control group. There was no correlation among ESM-1 levels, disease activity and CIMT. In order to reveal the pathological role of the ESM-1 levels in patients with AS need more studies.

scholarly journals Carotid Intima Media Thickness and Endothelial Function: Useful Surrogate Markers for Cardiovascular Risk in Rheumatoid Arthritis Patients

2021 ◽  
pp. 38-48
Author(s):  
Riham A. El-Sehly ◽  
Abeer A. Shahba ◽  
Raghda G. Elsheik ◽  
Mahmoud F. Selim
Keyword(s):  
Rheumatoid Arthritis ◽  
Endothelial Function ◽  
Disease Activity ◽  
Brachial Artery ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
University Hospital ◽  
Control Group ◽  
Carotid Imt ◽  
Media Thickness

Introduction: Cardiovascular diseases (CVDs) are the main cause of morbidity and mortality in RA disease. In active RA patients, the majority of cardiovascular deaths result from accelerates atherosclerosis. Aim of the Work: The aim of this work is to assess carotid intima media thickness (C-IMT) and endothelial function by brachial artery flow mediated dilatation (FMD) in Rheumatoid arthritis patients and relation to the disease activity. Subjects and Methods: Our study included 50 RA patients, from Tanta University Hospital. 47 women and 3 men and their age ranged from 30-62 years.  They were divided into group 1:  25 active RA patients, group 2:  25 inactive RA patients who were   diagnosed by American College of Rheumatology (ACR) revised criteria for diagnosis of RA 1987 and disease activity was evaluated using disease activity score 28(DAS28). Group 3: 25 normal subjects as a control group.  We measured C-IMT and FMD in all groups. Results: By comparing the groups, we found that active RA patients had increased C-IMT compared to inactive rheumatoid arthritis patients and controls which is indicator of atherosclerosis. FMD of the brachial artery impaired in RA patients compared to controls which is indicator of endothelial dysfunction. There was highly statistically significant relation between duration, activity of RA disease and atherosclerosis in RA patients. Conclusion: With increasing the frequency of atherosclerosis in asymptomatic RA patients, carotid IMT increased and FMD impaired when compared with general population. Active RA patients have increased carotid IMT and impaired FMD compared with inactive RA patients.

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