scholarly journals POS0205 AMELIORATION OF ENDOTHELIAL DYSFUNCTION WITH JAK INHIBITION IN RHEUMATOID ARTHRITIS: JAK CV-RISK REDUCTION STUDY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 318.2-319
Author(s):  
A. Syngle ◽  
N. Garg ◽  
K. Chauhan

Background:Cardiovascular (CV) disease is the leading cause of premature mortality and sudden death in Rheumatoid Arthritis (RA). Conventional CV risk factors and disease specific risk factors are responsible for endothelial dysfunction (ED) in RA. ED is the barometer of CV health and key initial event in atherosclerosis. Tofacitinib, a JAK inhibitor, is in clinical use since 2012 and has had the most extensive development program in RA, but its impact on ED has not yet been explored in humans.Objectives:To investigate the impact of tofacitinib on endothelial dysfunction in RAMethods:40 RA patients fulfilling the 2010 Rheumatoid Arthritis classification criteria with active disease (DAS28>3.2) were randomized to receive 24 weeks of treatment with Tofacitinib (5mg bd, n=20) and placebo (n=20) as an adjunct to existing stable antirheumatic drugs. Primary endpoints included endothelial dysfunction assessed by FMD using Angiodefender and lipids were estimated at baseline and after 12 weeks of treatment. The secondary end points included: DAS28, ESR, CRP, HAQ-DI and cardiovascular risk using SCORE chart assessed at week 0 and 12.Results:At baseline, endothelial function was impaired and levels of inflammatory measures were elevated in both groups. CV risk SCORE was high and HAQ-DI was impaired at baseline. After treatment, FMD improved significantly in the tofacitinib group from (8.16±1.38% to 10.98±2.33%, p≤0.05) as compared to placebo (7.12±0.25% to 8.04±0.30%, p=0.35) (Fig. 1A). DAS28 (Fig. 1B), ESR and CRP (Fig. 1C) levels improved significantly in tofacitinib group as compared to placebo (p≤0.05). Tofacitinib significantly decreased HAQ-DI and SCORE (Fig. 1D) values as compared to placebo. There was significant increase in HDL (p≤0.05) after treatment with tofacitinib as compared to placebo. After 12 weeks of treatment, FMD and HDL increased by 34.55% and 13.58% respectively where as DAS28, ESR and CRP decreased by 37.40%, 36.10% and 76.59% respectively in the tofacitinib group. Significant negative correlation was observed between FMD and DAS28 (r= -0.50, p≤0.05) and CRP (r= -52, p≤0.05) after treatment with tofacitinib where as no such correlation was found in placebo group.Figure 1.Impact of Tofacitinib on FMD, DAS 28, CRP & SCOREConclusion:First study to show that tofacitinib, apart from its anti inflammatory activity, improves endothelial dysfunction and cardiovascular risk in RA. Thus, JAK inhibition with tofacitinib has vasculoprotective and cardioprotective effect mediated through anti-inflammatory and probably other mechanisms. This study would stimulate further research in exploring the vasculoprotective and cardioprotective potential of tofacitinib in RA.References:[1]Tofacitinib reversed endothelial dysfunction in rheumatoid arthritis: mechanistic insights from the rat adjuvant-induced arthritis model. http://dx.doi.org/10.1136/annrheumdis-2020-eular.2747Disclosure of Interests:None declared

2020 ◽  
pp. 32-44
Author(s):  
D. I. Trukhan ◽  
D. S. Ivanova ◽  
K. D. Belus

Rheumatoid arthritis is a frequent and one of the most severe immuno-inflammatory diseases in humans, which determines the great medical and socio-economic importance of this pathology. One of the priority problems of modern cardiac rheumatology is an increased risk of cardiovascular complications in rheumatoid arthritis. In patients with rheumatoid arthritis, traditional cardiovascular risk factors for cardiovascular diseases (metabolic syndrome, obesity, dyslipidemia, arterial hypertension, insulin resistance, diabetes mellitus, smoking and hypodynamia) and a genetic predisposition are expressed. Their specific features also have a certain effect: the “lipid paradox” and the “obesity paradox”. However, chronic inflammation as a key factor in the development of progression of atherosclerosis and endothelial dysfunction plays a leading role in morbidity and mortality from cardiovascular diseases in rheumatoid arthritis. This review discusses the effect of chronic inflammation and its mediators on traditional cardiovascular risk factors and its independent significance in the development of CVD. Drug therapy (non-steroidal anti-inflammatory drugs, glucocorticosteroids, basic anti-inflammatory drugs, genetically engineered biological drugs) of the underlying disease also has a definite effect on cardiovascular risk factors in patients with rheumatoid arthritis. A review of studies on this problem suggests a positive effect of pharmacological intervention in rheumatoid arthritis on cardiovascular risk factors, their reduction to a level comparable to the populations of patients not suffering from rheumatoid arthritis. The interaction of rheumatologists, cardiologists and first-contact doctors (therapist and general practitioner) in studying the mechanisms of the development of atherosclerosis in patients with rheumatoid arthritis will allow in real clinical practice to develop adequate methods for the timely diagnosis and prevention of cardiovascular diseases in patients with rheumatoid arthritis.


2015 ◽  
Vol 78 (1) ◽  
Author(s):  
Donatella Ruggiero ◽  
Gianluigi Savarese ◽  
Roberto Formisano ◽  
Ada Bologna ◽  
Giacomo Mattiello ◽  
...  

Aim: to evaluate endothelial function (EF) in diabetic and non-diabetic patients without CAD by peripheral artery tonometry (PAT) technique. Methods: a cohort of 94 patients (55 men and 39 postmenopausal women; mean age 63±9 years) undergoing coronary angiography was divided into 2 groups: 58 patients with DM and (group 1) and 36 patients without DM. Endothelial dysfunction (ED) was assessed by digital pulse amplitude, using a fingertip peripheral arterial tonometry (PAT). As a measure of ED, reactive hyperemia index (RHI) was calculated as the ratio of the digital pulse volume during reactive hyperemia following 5 min ischemia and its basal value. Results: prevalence of cardiovascular risk factors was similar between the two groups. RHI values were significantly lower in diabetic patients compared to non-diabetics (1.72±0.34 vs 2.00±0.44; p<0.005) and they correlated with levels of glycosylated hemoglobin (p=0.05; r=-0.266). Conclusion: despite similar level of other risk factors, EF was much more impaired in diabetic patients than in non-diabetics. These evidences further support the impact of DM on cardiovascular risk.


2012 ◽  
Vol 10 (5) ◽  
pp. 639-646 ◽  
Author(s):  
Cecilia Chighizola ◽  
Tommaso Schioppo ◽  
Francesca Ingegnoli ◽  
Pier Luigi Meroni

2020 ◽  
Vol 16 ◽  
Author(s):  
Rahil Taheri ◽  
Shahram Molavynejad ◽  
Parvin Abedi ◽  
Elham Rajaei ◽  
Mohammad Hosein Haghighizadeh

Aim: The aim of this study was to investigate the effect of dietary education on cardiovascular risk factors in patients with rheumatoid arthritis. Method: In this randomized clinical trial, 112 patients with rheumatoid arthritis were randomly assigned into two groups, intervention and control. Dietary education was provided for the intervention group in 4 sessions; anthropometric measurements, serum levels of RF, triglycerides, cholesterol, HDL, LDL, and fasting blood sugar were measured before and three months after intervention. Data was analyzed using SPSS software and appropriate statistical tests. Results: The mean of total cholesterol (p <0.001), triglycerides (p = 0.004), LDL (p <0.001), systolic blood pressure (p = 0.001), diastolic blood pressure (p = 0.003), FBS and BMI (p <0.001) were decreased significantly in the intervention group after education compared the control group. Conclusion: Traditional care for rheumatoid arthritis patients is not enough. Patients need more education in order to improve their situation.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 526.1-526
Author(s):  
L. Nacef ◽  
H. Riahi ◽  
Y. Mabrouk ◽  
H. Ferjani ◽  
K. Maatallah ◽  
...  

Background:Hypertension, diabetes, and dyslipidemia are traditional risk factors of cardiac events. Carotid ultrasonography is an available way to detect subclinical atherosclerosis.Objectives:This study aimed to compare the intima-media thickness in RA patients based on their personal cardiovascular (CV) history of hypertension (hypertension), diabetes, and dyslipidemia.Methods:The present study is a prospective study conducted on Tunisian RA patients in the rheumatology department of Mohamed Kassab University Hospital (March and December 2020). The characteristics of the patients and those of the disease were collected.The high-resolution B-mode carotid US measured the IMT, according to American Society of Echocardiography guidelines. The carotid bulb below its bifurcation and the internal and external carotid arteries were evaluated bilaterally with grayscale, spectral, and color Doppler ultrasonography using proprietary software for carotid artery measurements. IMT was measured using the two inner layers of the common carotid artery, and an increased IMT was defined as ≥0.9 mm. A Framingham score was calculated to predict the cardiovascular risk at 10-year.Results:Forty-seven patients were collected, 78.7% of whom were women. The mean age was 52.5 ±11.06 [32-76]. The rheumatoid factor (RF) was positive in 57.8% of cases, and anti-citrullinated peptide antibodies (ACPA) were positive in 62.2% of cases. RA was erosive in 81.6% of cases. Hypertension (hypertension) was present in 14.9% of patients, diabetes in 12.8% of patients, and dyslipidemia in 12.8% of patients. Nine patients were active smokers. The mean IMT in the left common carotid (LCC) was 0.069 ±0.015, in the left internal carotid (LIC) was 0.069 ±0.015, in the left external carotid (LEC) was 0.060 ±0.023. The mean IMT was 0.068 ±0.01 in the right common carotid (RCC), 0.062 ±0.02 in the right internal carotid (RIC), and 0.060 ±0.016 in the right external carotid (REC). The IMT was significantly higher in the left common carotid (LCC) in patients with hypertension (p=0.025). There was no significant difference in the other ultrasound sites (LIC, LEC, RCC, RIC, and REC) according to the presence or absence of hypertension. The IMT was also significantly increased in patients with diabetes at LCC (p=0.017) and RIC (p=0.025). There was no significant difference in the IMT at different ultrasound sites between patients with and without dyslipidemia.Conclusion:Hypertension was significantly associated with the increase in IMT at the LCC level in RA patients. Diabetes had an impact on IMT in LCC and RIC. However, dyslipidemia did not affect the IMT at the different ultrasound sites.References:[1]S. Gunter and al. Arterial wave reflection and subclinical atherosclerosis in rheumatoid arthritis. Clinical and Experimental Rheumatology 2018; 36: Clinical E.xperimental.[2]Aslan and al. Assessment of local carotid stiffness in seronegative and seropositive rheumatoid arthritis. SCANDINAVIAN CARDIOVASCULAR JOURNAL, 2017.[3]Martin I. Wah-Suarez and al, Carotid ultrasound findings in rheumatoid arthritis and control subjects: A case-control study. Int J Rheum Dis. 2018;1–7.[4]Gobbic C and al. Marcadores subclínicos de aterosclerosis y factores de riesgo cardiovascular en artritis temprana. Subclinical markers of atherosclerosis and cardiovascular risk factors in early arthritis marcadores subclínicos de aterosclerose e fatores de risco cardiovascular na artrite precoce.Disclosure of Interests:None declared


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 973-973
Author(s):  
R. Gonzalez Mazario ◽  
J. J. Fragio-Gil ◽  
P. Martinez Calabuig ◽  
E. Grau García ◽  
M. De la Rubia Navarro ◽  
...  

Background:Cardiovascular disease (CV) is the most frequent cause of death in rheumatoid arthritis (RA) patients. It is well known that RA acts as an independent cardiovascular risk factor.Objectives:To assess the CV risk in RA patients using carotid ultrasonography (US) additionally to the traditional CV risk factors.Methods:A prospective transversal case control study was performed, including adult RA patients who fulfilled ACR/EULAR 2010 criteria and healthy controls matched according to CV risk factors. Population over 75 years old, patients with established CV disease and/or chronic kidney failure (from III stage) were excluded. The US evaluator was blinded to the case/control condition and evaluated the presence of plaques and the intima-media thickness. Statistical analysis was performed with R (3.6.1 version) and included a multivariate variance analysis (MANOVA) and a negative binomial regression adjusted by confounding factors (age, sex and CV risk factors).Results:A total of 200 cases and 111 healthy controls were included in the study. Demographical, clinical and US data are exposed in table 1. Not any difference was detected in terms of CV risk factors between the cases and controls. In both groups a relationship between age, BMI and high blood pressure was detected (p<0.001).Table 1.Table 2.RA basal characteristicsDisease duration (years)16,98 (11,38)Erosions (X-Ray of hands/feet)163 (81,5%)Seropositive (RF/anti-CCP)146 (73%)Extra-articular symptoms44 (22%)Intersticial difusse lung disease10 (5%)Rheumatoid nodules14 (7%)Prednisone use103 (51,5%)Median dose of Prednisone last year (mg)2,34 (2,84)sDMARDsMethotrexate104 (52%)Leflunomide29 (14,5%)Hydroxycloroquine9 (4,5%)bDMARDs89 (44,5%) TNFi41 (20,5%) Abatacept15 (7,5%) IL6i22 (11%) RTX11 (5,5%)JAKi26 (13%) Baricitinib11 (5,5%) Tofacitinib15 (7,5%)DAS 28-ESR3,1 (2,3, 3,9)SDAI7,85 (4,04, 13,41)HAQ0,88 (0,22, 1,5)RF (U/mL)51 (15, 164,25)Anti-CCP (U/mL)173 (22, 340)Patients showed higher intima-media (both right and left) thickness compared to controls (p<0.006). Moreover it was also related to the disease duration and DAS28 score (p<0.001). A higher plaque account was noted in cases(p<0.004) and it was also related to the disease duration (p<0.001).Conclusion:RA implies a higher CV risk. Traditional CV risk factors explains only partially the global risk. These findings support that RA acts as an independent cardiovascular risk factor.Disclosure of Interests:None declared


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