Cardiovascular Risk In Rheumatoid Arthritis Research Articles

Nesfatin-1 and visfatin expression is associated with reduced atherosclerotic disease risk in patients with rheumatoid arthritis

Nesfatin is an anti-inflammatory molecule that reduces atherosclerotic cardiovascular risk. By contrast, visfatin has pro-inflammatory properties and is pro-atherogenic. We examined the potential impact of nesfatin and visfatin on atherosclerotic disease in 232 (113 black and 119 white) consecutive rheumatoid arthritis (RA) patients from 2 centers. Independent relationships of nesfatin and visfatin concentrations with metabolic risk factors, endothelial activation, carotid atherosclerosis and altered plaque stability were determined in multivariable regression models. Rheumatoid factor (RF) positivity was associated with both nesfatin (β = 0.650, p < 0.0001) and visfatin levels (β = 0.157, p = 0.03). Visfatin concentrations were related to increased diastolic blood pressure (β = 4.536, p = 0.01) and diabetes prevalence (β = 0.092, p = 0.04). Nesfatin levels were associated with reduced carotid intima-media thickness (β = −0.017, p = 0.008). Nesfatin (β = 0.116, p = 0.001) and visfatin concentrations (β = 0.234, p = 0.001) were related to those of matrix metalloproteinase-2 (MMP-2), a plaque stability mediator. Nesfatin and visfatin concentrations were directly correlated (Spearman’s rho = 0.516). The nesfatin-MMP-2 and visfatin-MMP-2 relations were both stronger in RF negative compared to RF positive patients (interaction p = 0.01 and p = 0.04, respectively). Nesfatin is associated with reduced atherosclerosis and increased plaque stability mediator levels in RA. Visfatin is related to adverse cardio-metabolic risk in RA. Increased MMP-2 expression in relation to visfatin may represent a compensatory mechanism aimed at reducing cardiovascular risk in RA.

The Role of Statins in Disease Modification and Cardiovascular Risk in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an autoimmune, inflammatory disorder associated with excess cardiovascular morbidity and mortality. A complex interplay between traditional risk factors (dyslipidemia, insulin resistance, arterial hypertension, obesity, smoking) and chronic inflammation is implicated in the development of premature atherosclerosis and consequently in the higher incidence of cardiovascular events observed in RA patients. Despite the acknowledgment of elevated cardiovascular risk among RA individuals, its management remains suboptimal. While statin administration has a crucial role in primary and secondary cardiovascular disease prevention strategies as lipid modulating factors, there are limited data concerning the precise benefit of such therapy in patients with RA. Systemic inflammation and anti-inflammatory treatments influence lipid metabolism, leading to variable states of dyslipidemia in RA. Hence, the indications for statin therapy for cardiovascular prevention may differ between RA patients and the general population and the precise role of lipid lowering treatment in RA is yet to be established. Furthermore, some evidence supports a potential beneficial impact of statins on RA disease activity, attributable to their anti-inflammatory and immunomodulatory properties. This review discusses existing data on the efficacy of statins in reducing RA-related cardiovascular risk as well as their potential beneficial effects on disease activity.

Lipids in RA: Is Less Not Necessarily More?

In rheumatoid arthritis (RA), lipid levels are dynamic and can fluctuate along with changes in inflammation. A reduction in inflammation, most commonly as a result of disease-modifying anti-rheumatic drug (DMARD) therapy, is associated with increases in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). In this review, we discuss new evidence shedding light on the potential mechanism underlying changes in lipid levels observed with changes in inflammation. Measured lipid levels in the blood are a result of a balance between synthesis and catabolism or absorption. Recent human studies in active RA show that the catabolic rates of lipids are higher than expected compared to expected rates in the general population. DMARD therapy appears to allow a return to baseline lower catabolic rates, resulting in an apparent increase in lipids. Increases in lipids observed with control of inflammation and RA treatment suggest a return to homeostasis. Studies are underway to understand the overall impact on cardiovascular risk in RA when lipid levels increase as a result of controlling inflammation.

High Expression of STAT3 in Subcutaneous Adipose Tissue Associates with Cardiovascular Risk in Women with Rheumatoid Arthritis.

Despite the predominance of female patients and uncommon obesity, rheumatoid arthritis (RA) is tightly connected to increased cardiovascular morbidity. The aim of this study was to investigate transcriptional activity in the subcutaneous white adipose tissue (WAT) with respect to this disproportionate cardiovascular risk (CVR) in RA. CVR was estimated in 182 female patients, using the modified Systematic Coronary Risk Evaluation scale, and identified 93 patients with increased CVR. The overall transcriptional activity in WAT was significantly higher in patients with CVR and was presented by higher serum levels of WAT products leptin, resistin and IL-6 (all, p < 0.001). CVR was associated with high WAT-specific transcription of the signal transducer and activator of transcription 3 (STAT3) and the nuclear factor NF-kappa-B p65 subunit (RELA), and with high transcription of serine-threonine kinase B (AKT1) in leukocytes. These findings suggest Interleukin 6 (IL-6) and leptin take part in WAT-specific activation of STAT3. The binary logistic regression analysis confirmed an independent association of CVR with IL-6 in serum, and with STAT3 in WAT. The study shows an association of CVR with transcriptional activity in WAT in female RA patients. It also emphasizes the importance of STAT3 regulatory circuits for WAT-related CVR in RA.

Lipids and lipid changes with synthetic and biologic disease-modifying antirheumatic drug therapy in rheumatoid arthritis: implications for cardiovascular risk.

To highlight recently published studies addressing lipid changes with disease-modifying antirheumatic drug use and outline implications on cardiovascular outcomes in rheumatoid arthritis (RA). Growing evidence suggests lower lipid levels are present in patients with active RA vs. general population, and significant modifications of lipid profile with inflammation suppression. Increase in lipid levels in patients with RA on synthetic and biological disease-modifying antirheumatic drugs may be accompanied by antiatherogenic changes in lipid composition and function. The impact of lipid changes on cardiovascular outcomes in RA is a subject of active research. The role of lipids in cardiovascular risk in RA may be overpowered by the benefits of inflammation suppression with antirheumatic medication use. Recommendations on lipid management in RA are evolving but uncertainty exists regarding frequency of lipid testing and goals of treatment. Knowledge about quantitative and qualitative lipid changes in RA is expanding. The relative role of lipids in cardiovascular risk in the context of systemic inflammation and antirheumatic therapy remains uncertain, delaying development of effective strategies for cardiovascular risk management in RA. Studies are underway to address these knowledge gaps and may be expected to inform cardiovascular risk management in RA and the general population.

Cardiovascular risk in patients with rheumatoid arthritis.

Substantial epidemiologic data have shown an increased risk of cardiovascular (CV) disease in rheumatoid arthritis (RA) patients. Traditional CV risk factors may partly contribute to CV disease in RA; however, current evidence underlines the important role of inflammation in the pathogenesis of atherosclerosis and amplification of CV risk. Interplays between inflammation and lipid metabolism in the development of atherosclerosis have been established by recent scientific advances. Atherosclerosis is currently viewed as an inflammatory disease, and modifications of lipoproteins during inflammation accelerate atherogenesis. The role of inflammation in the increased CV risk in RA has been further demonstrated by the CV protective effect of methotrexate and TNF antagonists, particularly in patients responding to these treatments. The management of CV risk in RA should include the use of effective disease-modifying anti-rheumatic drugs to control disease activity and the treatment of traditional CV risk factors.

Measurement of carotid intima media thickness, a marker of cardiovascular risk in Rheumatoid Arthritis

Abstract Background Rheumatoid Arthritis (RA) is a multisystem disease. In addition to the involvement of joints, eyes, pleura, less known are effects on the heart. This study aims to generate more data by measuring carotid intima media thickness (CIMT) in patients with RA. Methods A cross sectional study performed at Dr Baba Saheb Ambedkar Hospital and Medical College, a tertiary care referral centre which included 80 patients with RA as cases divided further into 2 groups. Group 1 had 50 with disease duration more than 5 years while group 2 included 30 with duration less than 5 years. 40 healthy age and sex matched subjects were taken as controls. Cases and controls symptomatic for atherosclerosis or with risk factors for atherosclerosis were excluded. Both groups were subjected to carotid ultrasound examination. Results The study population included 90% females and 10% males. The mean CIMT of RA patients (0.6900 ± 0.197 mm) was significantly greater than the controls (0.3875 ± 0.082), p Conclusion Patients with RA exhibit premature atherosclerosis by way of increased CIMT, and hence are at increased cardiovascular risk as compared to age and sex matched controls.

Association of Paraoxonase 1 Polymorphism and Serum 25-Hydroxyvitamin D with the Risk of Cardiovascular Disease in Patients with Rheumatoid Arthritis.

Patients with rheumatoid arthritis (RA) have significantly increased cardiovascular (CV) morbidity and mortality that are not accounted for by traditional risk factors alone. Paraoxonase 1 (PON1) and 25-hydroxyvitamin D have been shown to be involved in the pathogenesis of CV diseases. Objective: This study aimed to investigate PON1 gene polymorphism and serum 25-hydroxyvitamin D concentrations in RA patients, and to determine their association with CV risk in RA. Serum samples from 46 RA patients and 45 healthy controls were tested for PON1 R192Q genotypes and serum vitamin D concentrations. The cardiovascular risks were assessed by Q-risk. Lipoprotein cholesterol levels, traditional CV risk factors, medication use, and RA disease activity status were also assessed. PON1 polymorphism and low serum 25-hydroxyvitamin D were significantly associated with increased CV risk (p < 0.05). Compared to patients with either the PON1 QQ genotype or the QR genotype, patients with the RR genotype demonstrated decreased CV risk on multivariate analysis, controlling for traditional CV risk factors, C-reactive protein levels, prednisone use, and cholesterol-lowering medication use (p < 0.05). There was a relationship of the genetic determinants of paraoxonase 1 (PON1 192) and serum 25-hydroxyvitamin D to CV risk in RA patients. Paired measurement of paraoxonase 1 genotype and serum 25-hydroxyvitamin D can be used as biomarkers of CV risk in RA patients.

Methotrexate and Cardiovascular Protection: Current Evidence and Future Directions

Patients with autoimmune rheumatic conditions, particularly rheumatoid arthritis, have an increased cardiovascular risk when compared with the general population. Methotrexate is a relatively old, yet effective, immunomodulatory drug for the management of autoimmune and chronic inflammatory disorders, such as rheumatoid arthritis, particularly in terms of symptom control, quality of life, and disease progression. Recent meta-analyses have also shown that methotrexate treatment is associated with a lower risk of cardiovascular events when compared with other disease-modifying antirheumatic drugs. This suggests that methotrexate might exert specific protective effects against atherosclerosis and thrombosis. This mini-review discusses the mechanisms associated with the increased cardiovascular risk in rheumatoid arthritis, the pharmacokinetics and pharmacodynamics of methotrexate, the available evidence on the in vitro and in vivo effects of methotrexate on modifiable cardiovascular risk factors, and suggest...

Increased sympathetic nerve activity and reduced cardiac baroreflex sensitivity in rheumatoid arthritis.

Key points Rheumatoid arthritis (RA) is a chronic inflammatory condition associated with an increased risk of cardiovascular mortality.Increased sympathetic nerve activity and reduced cardiac baroreflex sensitivity heighten cardiovascular risk, althogh whether such autonomic dysfunction is present in RA is not known.In the present study, we observed an increased sympathetic nerve activity and reduced cardiac baroreflex sensitivity in patients with RA compared to matched controls.Pain was positively correlated with sympathetic nerve activity and negatively correlated with cardiac baroreflex sensitivity.The pattern of autonomic dysfunction that we describe may help to explain the increased cardiovascular risk in RA, and raises the possibility that optimizing pain management may resolve autonomic dysfunction in RA. Rheumatoid arthritis (RA) is a chronic inflammatory condition associated with increased cardiovascular morbidity/mortality and an incompletely understood pathophysiology. In animal studies, central and blood borne inflammatory cytokines that can be elevated in RA evoke pathogenic increases in sympathetic activity and reductions in baroreflex sensitivity (BRS). We hypothesized that muscle sympathetic nerve activity (MSNA) was increased and BRS decreased in RA. MSNA, blood pressure and heart rate (HR) were recorded in age‐ and sex‐matched RA‐normotensive (n = 13), RA‐hypertensive patients (RA‐HTN; n = 17), normotensive (NC; n = 17) and hypertensive controls (HTN; n = 16). BRS was determined using the modified Oxford technique. Inflammation and pain were determined using serum high sensitivity C‐reactive protein (hs‐CRP) and a visual analogue scale (VAS), respectively. MSNA was elevated similarly in RA, RA‐HTN and HTN patients (32 ± 9, 35 ± 14, 37 ± 8 bursts min–1) compared to NC (22 ± 9 bursts min–1; P = 0.004). Sympathetic BRS was similar between groups (P = 0.927), whereas cardiac BRS (cBRS) was reduced in RA, RA‐HTN and HTN patients [5(3–8), 4 (2–7), 6 (4–9) ms mmHg–1] compared to NC [11 (8–15) ms mmHg–1; P = 0.002]. HR was independently associated with hs‐CRP. Increased MSNA and reduced cBRS were associated with hs‐CRP although confounded in multivariable analysis. VAS was independently associated with MSNA burst frequency, cBRS and HR. We provide the first evidence for heightened sympathetic outflow and reduced cBRS in RA that can be independent of hypertension. In RA patients, reported pain was positively correlated with MSNA and negatively correlated with cBRS. Future studies should assess whether therapies to ameliorate pain and inflammation in RA restores autonomic balance and reduces cardiovascular events.

Cardiovascular risk in rheumatoid arthritis: assessment, management and next steps.

Rheumatoid arthritis (RA) is associated with increased cardiovascular (CV) morbidity and mortality which cannot be fully explained by traditional CV risk factors; cumulative inflammatory burden and antirheumatic medication-related cardiotoxicity seem to be important contributors. Despite the acknowledgment and appreciation of CV disease burden in RA, optimal management of individuals with RA represents a challenging task which remains suboptimal. To address this need, the European League Against Rheumatism (EULAR) published recommendations suggesting the adaptation of traditional risk scores by using a multiplication factor of 1.5 if two of three specific criteria are fulfilled. Such guidance requires proper coordination of several medical specialties, including general practitioners, rheumatologists, cardiologists, exercise physiologists and psychologists to achieve a desirable result. Tight control of disease activity, management of traditional risk factors and lifestyle modification represent, amongst others, the most important steps in improving CV disease outcomes in RA patients. Rather than enumerating studies and guidelines, this review attempts to critically appraise current literature, highlighting future perspectives of CV risk management in RA.

Romatoid artritte kardiyovasküler risk ve risk yönetimi

Romatoid artritte kardiyovasküler risk ve risk yönetimi

Disease Activity, Oxidized-LDL Fraction and Anti-Oxidized LDL Antibodies Influence Cardiovascular Risk in Rheumatoid Arthritis.

Patients with rheumatoid arthritis (RA) have a shortened lifespan compared to the general population. The high rate of premature mortality in the RA population can be attributed to cardiovascular disease (CVD). The aim of the study was to look for non-classic risk factors that can at least partially explain the enhanced cardiovascular (CV) risk in patients with RA. This was an observational study with 37 RA patients and 24 healthy volunteers as controls. The participants' medical history was taken, and systematic coronary risk evaluation (SCORE) and carotid ultrasonography examinations were performed on all the participants. Laboratory tests included antibodies anti-cyclic citrullinated peptide (anti-CCP), inflammatory markers, lipid level, oxidized low-density lipoprotein (oxLDL) level and the level of anti-oxLDL antibodies. Both SCORE and oxLDL fraction were elevated in RA patients as compared to the healthy controls (3.1 ± 3.7 vs. 0.8 ± 1.2, p = 0.005; and 0.029 ± 0.033% vs. 0.014 ± 0.006%, p = 0.04, respectively). In the RA group, the presence of anti-CCP was associated with thickening of the carotid intima-media complex and SCORE elevation. In the RA group, significant correlations were found between SCORE and mean carotid intima-media thickness (IMT; RP = 0.34, p = 0.040), disease activity score (RP = 0.42, p = 0.011), erythrocyte sedimentation rate (ESR; RP = 0.35, p = 0.036), and disease duration (RP = 0.52, p = 0.002). In RA patients with carotid plaques, the oxLDL fraction was significantly elevated in comparison to those without plaques (0.055 ± 0.070% vs. 0.022 ± 0.018%, p = 0.033). In the RA group, there was a significant negative correlation between mean carotid IMT and the serum concentration of anti-oxLDL antibodies (RP = -0.38, p = 0.02). No association was noted between the presence of rheumatoid nodules and SCORE or carotid IMT. Among RA patients, disease activity, ESR, disease duration, the presence of anti-CCP antibodies, the oxLDL fraction and the level of anti-oxLDL antibodies influence CV risk.

Le risque cardiovasculaire dans la spondyloarthrite axiale

An increased cardiovascular risk has been consistently reported in inflammatory rheumatic diseases. An important number of studies found the same higher cardiovascular risk in rheumatoid arthritis and systemic lupus erythematosus. On the contrary, the presence of this increase cardiac risk is less documented in ankylosing spondylitis (AS) with some contradictory information in the studies. This review aims to report the current data in 2014 on the high cardiovascular risk in AS, the prevalence of cardiovascular risk factors in this rheumatic disease, the cardiovascular effects of treatment and the guidelines for cardiovascular risk management.

Patients' Experiences of Nurse-Led Screening for Cardiovascular Risk in Rheumatoid Arthritis.

Patients with rheumatoid arthritis (RA) have increased morbidity and mortality due to cardiovascular disease (CVD). Screening for cardiovascular risk is recommended by the European League Against Rheumatism (EULAR). There is a lack of evidence of the experiences of RA patients who are screened for CVD. Such information is important in order to organize and further develop screening programmes for CVD in patients with RA. The aim of the present study was to explore RA patients' experiences of participation in nurse-led screening for CVD and to identify key issues for the future organization of screening programmes. Three qualitative focus group interviews were carried out with 14 outpatients diagnosed with RA. The participants were stratified into groups, depending on whether they had a low-to-moderate or high ten-year risk of cardiovascular death according to the European Systematic Coronary Risk Evaluation (SCORE) system. Data were analysed using meaning condensation to identify key themes. Five themes were identified: reactions to receiving the invitation to the screening consultation; screening consultation adapted to needs and RA; duration reflected needs; screening consultation brought a sense of relief; and motivation and sense of control. Regardless of their CV risk, the participants found it important that the screening consultation was adapted to their needs and their illness as RA had a major impact on their daily life. When planning future screening programmes for CVD for patients with RA, it is important that the screening consultation is individualized and tailored to patients' needs and their RA. Copyright © 2015 John Wiley & Sons, Ltd.

Prediction of cardiovascular risk in rheumatoid arthritis: performance of original and adapted SCORE algorithms

ObjectivesPredictive performance of cardiovascular disease (CVD) risk calculators appears suboptimal in rheumatoid arthritis (RA). A disease-specific CVD risk algorithm may improve CVD risk prediction in RA. The objectives of this...

Cardiovascular risk in rheumatoid arthritis: recent advances in the understanding of the pivotal role of inflammation, risk predictors and the impact of treatment.

Risk of cardiovascular (CV) disease is increased among RA patients. High inflammatory burden associated with RA appears to be a key driver of the increased cardiovascular risk. Inflammation is linked with accelerated atherosclerosis and associated with a paradoxical inversion of the relationship between CV risk and lipid levels in patients with untreated RA, recently coined the lipid paradox. Furthermore, the inflammatory burden is also associated with qualitative as well as quantitative changes in lipoproteins, with the anti-inflammatory and atheroprotective roles associated with high-density lipoprotein cholesterol significantly altered. RA therapies can increase lipid levels, which may reflect the normalization of lipids due to their inflammatory-dampening effects. However, these confounding influences of inflammation and RA therapies on lipid profiles pose challenges for assessing CV risk in RA patients and interpretation of traditional CV risk scores. In this review we examine the relationship between the increased inflammatory burden in RA and CV risk, exploring how inflammation influences lipid profiles, the impact of RA therapies and strategies for identifying and monitoring CV risk in RA patients aimed at improving CV outcomes.

SP0165 How to Evaluate Cardiovascular Risk in Patients with Inflammatory Joint Disease – A Review of the Evidence

The increased risk of cardiovascular (CV) morbidity and mortality in patients with rheumatoid arthritis (RA) has been known for decades [1]. CV disease is a major factor in the widening...

THU0490 Mthfr C677T Polymorphism but not DDAH Gene Variants Are Associated with Asymmetric Dimethylarginine in Patients with Rheumatoid Arthritis

BackgroundEndothelial dysfunction is highly prevalent in patients with Rheumatoid Arthritis (RA) contributing to the excess cardiovascular (CV) risk observed in this population. Assymetric dimethylarginine (ADMA) is an endogenous inhibitor of...

SAT0129 Whole Body DXA Bone Tissue and Cardiovascular Risk in Rheumatoid Arthritis

BackgroundAtherosclerosis and osteoporosis share an age-independent bidirectional correlation.[1] Rheumatoid arthritis (RA) represents a risk factor for both conditions. So far, only hip and lumbar spine indices were used in clinical...