Cardiovascular Disease Risk In Rheumatoid Arthritis Research Articles

Cardiovascular Risk in Rheumatoid Arthritis: Considerations on Assessment and Management.

In the context of holistic therapeutic practices, the cardiovascular risk of patients with rheumatoid arthritis (RA) needs to be addressed as a major factor of compromised disease prognosis and increased mortality. The elevated prevalence of cardiovascular disease (CVD) by more than twofold in RA has been attributed, inter alia, to chronic inflammation exacerbating arterial stiffness, increased onset of hypertension, dyslipidaemia and diabetes mellitus, sedentary lifestyle, and antirheumatic drug complications. CVD risk in RA can be currently assessed by practitioners through accessible adapted calculators, but it remains problematic as their diagnostic accuracy is not superior to calculators designed for the general population. Implementation of guideline-oriented personalised interventions remains the cornerstone for cardiovascular risk management in RA. Remarkably, there is lack of a consortium that brings together different health care providers engaged in the care of patients with RA (e.g., rheumatologists, cardiologists, general practitioners, etc), to guide cardiovascular risk assessment and management. This narrative review aims at providing an overview of current CVD risk assessment and management options, highlighting their pivotal role in the comprehensive treatment of RA patients.

Treating Cardiovascular Disease in the Inflammatory Setting of Rheumatoid Arthritis: An Ongoing Challenge.

Despite progress in treating rheumatoid arthritis, this autoimmune disorder confers an increased risk of developing cardiovascular disease (CVD). Widely used screening protocols and current clinical guidelines are inadequate for the early detection of CVD in persons with rheumatoid arthritis. Traditional CVD risk factors alone cannot be applied because they underestimate CVD risk in rheumatoid arthritis, missing the window of opportunity for prompt intervention to decrease morbidity and mortality. The lipid profile is insufficient to assess CVD risk. This review delves into the connection between systemic inflammation in rheumatoid arthritis and the premature onset of CVD. The shared inflammatory and immunologic pathways between the two diseases that result in subclinical atherosclerosis and disrupted cholesterol homeostasis are examined. The treatment armamentarium for rheumatoid arthritis is summarized, with a particular focus on each medication's cardiovascular effect, as well as the mechanism of action, risk-benefit profile, safety, and cost. A clinical approach to CVD screening and treatment for rheumatoid arthritis patients is proposed based on the available evidence. The mortality gap between rheumatoid arthritis and non-rheumatoid arthritis populations due to premature CVD represents an urgent research need in the fields of cardiology and rheumatology. Future research areas, including risk assessment tools and novel immunotherapeutic targets, are highlighted.

Clinical implications of seropositive and seronegative autoantibody status in rheumatoid arthritis patients: A comparative multicentre observational study.

Rheumatoid factor (RF) and anti-cyclic citrullinated protein (anti-CCP) have been used to improve the diagnosis and prognosis of rheumatoid arthritis (RA). However, their association with RA disease phenotypes, individually and in combination, is not well studied. The aim of the study was to compare patients' and disease characteristics, activity and severity in double seronegative (DNRA), single seropositive RF, single seropositive anti-CCP and double seropositive (DPRA) patients. Adults subjects with RA from Egyptian College of Rheumatology (ECR) database who had RF and anti-CCP results available were included. Demographic, clinical features, disease activity score 28 (DAS28), Health Assessment Questionnaire (HAQ) and laboratory data were collected and compared among different RA groups. 5268 RA patients with mean age of 44.9±11.6 years, and 4477 (85%) were females. 2900 (55%) had DPRA, 892 (16.9%) had single positive RF, 597 (11.3%) had single positive anti-CCP while 879 (16.7%) had DNRA. Patients with DPRA had significantly high percentage of metabolic syndrome (19.3%, P < 0.001), and functional impairment using HAQ (P = 0.01). Older age (RRR [relative risk ratio]: 1.03, 95%CI: 1.0, 1.0, P = 0.029), greater DAS28 (RRR: 1.51, 95%CI: 1.2, 1.9, P < 0.001), higher steroid use (RRR: 2.4, 95%CI: 1.36, 4.25, P = 0.002) were at higher risk of DPRA while longer disease duration (RRR: 1.08, 95%CI: 1.01, 1.16, P = 0.017) and fibromyalgia syndrome (RRR: 2.54, 95%CI: 1.10, 5.88, P = 0.028) were associated with higher odds of single positive RF status. Dual antibody-positive status has higher disease activity and severity, and higher chance of development of metabolic syndrome; highlighting the implicated role of inflammation, atherogenesis and cardiovascular disease risk in RA.

Dyslipidemia in rheumatoid arthritis: the possible mechanisms

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease, of which the leading cause of death is cardiovascular disease (CVD). The levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) in RA decrease especially under hyperinflammatory conditions. It is conflictive with the increased risk of CVD in RA, which is called “lipid paradox”. The systemic inflammation may explain this apparent contradiction. The increased systemic proinflammatory cytokines in RA mainly include interleukin-6(IL-6)、interleukin-1(IL-1)and tumor necrosis factor alpha(TNF-α). The inflammation of RA cause changes in the subcomponents and structure of HDL particles, leading to a weakened anti-atherosclerosis function and promoting LDL oxidation and plaque formation. Dysfunctional HDL can further worsen the abnormalities of LDL metabolism, increasing the risk of cardiovascular disease. However, the specific mechanisms underlying lipid changes in RA and increased CVD risk remain unclear. Therefore, this article comprehensively integrates the latest existing literature to describe the unique lipid profile of RA, explore the mechanisms of lipid changes, and investigate the impact of lipid changes on cardiovascular disease.

Skin microcirculation dynamics are impaired in patients with rheumatoid arthritis and no cardiovascular comorbidities.

Rheumatoid arthritis (RA) is associated with increased cardiovascular disease (CVD) risk. Microvascular endothelial dysfunction contributes to the development of vascular injury and subsequent CVD. We hypothesised that RA patients exhibit blunted microvascular reactivity regardless of CVD risk factors and investigated potential associations with coronary microvascular perfusion and surrogate markers of CVD. This case-control study recruited RA patients and non-RA individuals in the absence of cardiovascular comorbidities. Skin microvascular reactivity was dynamically assessed using laser speckle contrast imaging coupled with post-occlusive reactive hyperaemia protocol. Applanation tonometry was applied to assess subendocardial viability ratio, an index of myocardial microvascular perfusion, and central arterial stiffness [carotid-femoral pulse wave velocity (PWV), augmentation index]. Peripheral arterial stiffness (carotid PWV, β-stiffness index) and carotid atherosclerosis (intima-media thickness) were assessed with carotid ultrasound software. Skin microvascular responses before and following reperfusion [baseline flux, occlusion flux, time-to-peak, peak magnitude, peak-to-baseline magnitude, baseline cutaneous vascular conductance (CVC), and percentage increase in CVC] were significantly impaired in RA patients (n=35) compared to controls (n=35). Presence of RA independently predicted altered microvascular reactivity in multivariate analysis. Skin microcirculation dynamics significantly correlated with coronary microvascular perfusion and peripheral arterial stiffness, yet not carotid atherosclerosis, even after adjustment for CVD risk factors. Patients with RA present impaired microvascular reactivity regardless of CVD risk factors at a preclinical stage preceding CVD. Assessment of skin microvascular dysfunction may reflect a state of generalised vasculopathy, including myocardial microvascular abnormalities, and serve as a non-invasive surrogate indicator of CVD risk in RA.

Antirheumatic treatment is associated with reduced serum Syndecan-1 in Rheumatoid Arthritis.

The endothelial glycocalyx (EG) is essential for proper function of the endothelium and for vascular integrity, but its role in premature atherogenesis in rheumatoid arthritis (RA) has not been studied yet. EG impairment can play a role in pathogenesis of vascular disease, and one of its characteristics is shedding of syndecan-1 from endothelial cells. Syndecan-1 shedding is mediated by matrix metalloproteinase-9 (MMP-9) and counteracted by tissue inhibitor of metalloproteinases (TIMP)-1. Cardiovascular disease risk in RA is reversible by disease modifying antirheumatic drugs (DMARDs), but the exact modes of action are still unclear. Therefore, we examined effects of DMARDs on syndecan-1, MMP-9 and TIMP-1 in RA patients, and searched for associations between these parameters and inflammatory activity. From the observational PSARA study, we examined 39 patients starting with methotrexate (MTX) monotherapy (in MTX naïve patients, n = 19) or tumor necrosis factor inhibitors (TNFi) in combination with MTX (in MTX non-responders, n = 20) due to active RA. Serum syndecan-1, MMP-9 and TIMP-1 were measured at baseline and after six weeks of treatment. Serum syndecan-1 (p = 0.008) and TIMP-1 (p<0.001) levels decreased after six weeks of anti-rheumatic treatment. Levels of MMP-9 also decreased, but the difference was not statistically significant. The improvement in syndecan-1 levels were independent of changes in inflammatory activity. There was no significant difference in changes in syndecan-1 levels from baseline to 6 weeks between the MTX and TNFi groups, however the change was significant within the MTX group. Six weeks of antirheumatic treatment was associated with reduction in serum levels of syndecan-1, which might reflect reduced syndecan-1 shedding from EG. Thus, it is possible that EG-preserving properties of DMARDs might contribute to their cardioprotective effects. These effects may be at least partly independent of their anti-inflammatory actions. Our findings do not support the notion that syndecan-1 shedding in RA is mediated mainly by increased MMP-9 or decreased TIMP-9 serum concentration.

Low Soluble Receptor for Advanced Glycation End Products Precedes and Predicts Cardiometabolic Events in Women With Rheumatoid Arthritis.

Background: Cardiovascular disease (CVD) causes premature mortality in rheumatoid arthritis (RA). Levels of soluble (s)RAGE change with aging, hypertension and hypercholesterolemia. We assessed whether sRAGE was associated with increased risk of CVD in RA patients.Methods: Serum sRAGE was measured in 184 female RA patients and analyzed with respect to CVD risk estimated by the Framingham algorithm (eCVR), metabolic profile and inflammation. Levels of sRAGE in 13 patients with known cardio-metabolic morbidity defined the cut-off for low sRAGE. Prospective 5-year follow-up of new CV and metabolic events was completed.Results: Low sRAGE was significantly associated with previous history and with new imminent cardiometabolic events in the prospective follow-up of RA patients. In both cases, low sRAGE reflected higher estimation of CVR in those patients. Low sRAGE was attributed to adverse metabolic parameters including high fasting plasma glucose and body fat content rather than inflammation. The association of sRAGE and poor metabolic profile was prominent in patients younger than 50 years.Conclusions: This study points at low sRAGE as a marker of metabolic failure developed during chronic inflammation. It highlights the importance for monitoring metabolic health in female RA patients for timely prevention of CVD.Trial registration: ClinicalTrials.gov with ID NCT03449589. Registered 28, February 2018.

Cardiovascular Disease in Rheumatoid Arthritis: Risk Factors, Autoantibodies, and the Effect of Antirheumatic Therapies.

Objective:To scope the current published evidence on cardiovascular risk factors in rheumatoid arthritis (RA) focusing on the role of autoantibodies and the effect of antirheumatic agents.Methods:Two reviews were conducted in parallel: A targeted literature review (TLR) describing the risk factors associated with cardiovascular disease (CVD) in RA patients; and a systematic literature review (SLR) identifying and characterizing the association between autoantibody status and CVD risk in RA. A narrative synthesis of the evidence was carried out.Results:A total of 69 publications (49 in the TLR and 20 in the SLR) were included in the qualitative evidence synthesis. The most prevalent topic related to CVD risks in RA was inflammation as a shared mechanism behind both RA morbidity and atherosclerotic processes. Published evidence indicated that most of RA patients already had significant CV pathologies at the time of diagnosis, suggesting subclinical CVD may be developing before patients become symptomatic. Four types of autoantibodies (rheumatoid factor, anti-citrullinated peptide antibodies, anti-phospholipid autoantibodies, anti-lipoprotein autoantibodies) showed increased risk of specific cardiovascular events, such as higher risk of cardiovascular death in rheumatoid factor positive patients and higher risk of thrombosis in anti-phospholipid autoantibody positive patients.Conclusion:Autoantibodies appear to increase CVD risk; however, the magnitude of the increase and the types of CVD outcomes affected are still unclear. Prospective studies with larger populations are required to further understand and quantify the association, including the causal pathway, between specific risk factors and CVD outcomes in RA patients.

THU0132 ASSOCIATION OF RHEUMATOID ARTHRITIS AND DEMENTIA: A NATIONWIDE POPULATION-BASED STUDY

Background: Cumulative inflammation correlates with coronary plaque increase and cardiovascular disease (CVD) events in rheumatoid arthritis (RA). Coronary plaque progression predicts CVD risk beyond baseline burden in general patients. Statins inhibit plaque progression and are effective for CVD prevention in general patients. Nevertheless, their impact on coronary plaque trajectory and CVD risk in RA are less clear. Objectives: To explore if statin treatment may reduce CVD event risk, inhibit new plaque formation or promote the regression or protective calcification of prevalent atherosclerotic lesions in RA. We also evaluated whether statins moderate the effects of inflammation (CRP) on CVD risk and on coronary plaque progression. Methods: One hundred-fifty patients underwent computed tomography angiography for coronary atherosclerosis evaluation (total, non-calcified, mixed/calcified plaque); 101 had repeat assessments within 6.9±0.3 years to evaluate plaque progression. CVD events were prospectively recorded, including cardiac death, myocardial infarction, unstable angina, revascularization, stroke, claudication, and heart failure hospitalization. Framingham-D’Agostino score assessed clinical risk. Plaque burden was measured as segment stenosis score (cumulative stenosis). Robust cox proportional hazards regression models evaluated the effects of time-varying statin use, log-transformed time-varying CRP (mg/dL) and their interaction on CVD risk controlling for Framingham-D’Agostino score, plaque burden and time-varying bDMARD use. Per-segment robust logistic regression assessed the effect of statin duration (years), log-transformed time-averaged CRP, and their interaction on likelihood of plaque formation in segments without plaque, and plaque regression or calcification in segments with non-calcified lesions. Models accounted for clustering of coronary segments within patients and controlled for Framingham-D’Agostino score, total prednisone dose, bDMARD duration, and time between scans. Results: Sixteen patients incurred 19 CVD events. There was no main effect of current statin use on CVD risk (adjusted HR 1.10, 95% CI 0.33-3.67). However, there was an interaction between current statin use and time-varying CRP (p-interaction=0.030); higher time-varying CRP predicted greater CVD risk in patients not receiving statins (adjusted HR 2.78, 95% CI 1.01-7.65), but not current statin users (Figure 1A). Likewise, current statin use associated with lower CVD risk when patients had higher time-varying CRP (>0.5 mg/dL) but not when CRP was lower ( Conclusion: In RA, statins moderated the effect of CRP on CVD event risk and new plaque formation in coronary segments without plaque. Longer statin duration was also associated with an increased likelihood of protective calcification of non-calcified plaque. Disclosure of Interests: George Karpouzas Grant/research support from: Pfizer, Consultant of: Sanofi-Genzyme-Regeneron, Janssen, Speakers bureau: Sanofi-Genzyme-Regeneron, BMS, Sarah Ormseth: None declared, Elizabeth Hernandez: None declared, Matthew Budoff: None declared

THU0139 STATINS MODERATE THE EFFECT OF INFLAMMATION ON CORONARY PLAQUE PROGRESSION AND CARDIOVASCULAR DISEASE RISK IN RHEUMATOID ARTHRITIS

Background:Cumulative inflammation correlates with coronary plaque increase and cardiovascular disease (CVD) events in rheumatoid arthritis (RA). Coronary plaque progression predicts CVD risk beyond baseline burden in general patients. Statins inhibit plaque progression and are effective for CVD prevention in general patients. Nevertheless, their impact on coronary plaque trajectory and CVD risk in RA are less clear.Objectives:To explore if statin treatment may reduce CVD event risk, inhibit new plaque formation or promote the regression or protective calcification of prevalent atherosclerotic lesions in RA. We also evaluated whether statins moderate the effects of inflammation (CRP) on CVD risk and on coronary plaque progression.Methods:One hundred-fifty patients underwent computed tomography angiography for coronary atherosclerosis evaluation (total, non-calcified, mixed/calcified plaque); 101 had repeat assessments within 6.9±0.3 years to evaluate plaque progression. CVD events were prospectively recorded, including cardiac death, myocardial infarction, unstable angina, revascularization, stroke, claudication, and heart failure hospitalization. Framingham-D’Agostino score assessed clinical risk. Plaque burden was measured as segment stenosis score (cumulative stenosis). Robust cox proportional hazards regression models evaluated the effects of time-varying statin use, log-transformed time-varying CRP (mg/dL) and their interaction on CVD risk controlling for Framingham-D’Agostino score, plaque burden and time-varying bDMARD use. Per-segment robust logistic regression assessed the effect of statin duration (years), log-transformed time-averaged CRP, and their interaction on likelihood of plaque formation in segments without plaque, and plaque regression or calcification in segments with non-calcified lesions. Models accounted for clustering of coronary segments within patients and controlled for Framingham-D’Agostino score, total prednisone dose, bDMARD duration, and time between scans.Results:Sixteen patients incurred 19 CVD events. There was no main effect of current statin use on CVD risk (adjusted HR 1.10, 95% CI 0.33-3.67). However, there was an interaction between current statin use and time-varying CRP (p-interaction=0.030); higher time-varying CRP predicted greater CVD risk in patients not receiving statins (adjusted HR 2.78, 95% CI 1.01-7.65), but not current statin users (Figure 1A). Likewise, current statin use associated with lower CVD risk when patients had higher time-varying CRP (&gt;0.5 mg/dL) but not when CRP was lower (&lt;0.5 mg/dL, Figure 1B). Statin duration had no main effect on new plaque formation in segments without plaque at baseline (adjusted OR 1.13, 95% CI 0.95-1.05); however, statin use moderated the effect of time-averaged CRP on new plaque formation (p-interaction=0.030, Figure 2A). Time-averaged CRP associated with a higher likelihood of new plaque in patients receiving statins less than one year (adjusted OR 1.75, 95% CI 1.38-2.20) but not those treated for longer (adjusted OR 1.26, 95% CI 0.78-2.02). In segments with non-calcified plaque, longer statin duration predicted protective calcification (adjusted OR 1.28, 95% CI 1.07-1.53, Figure 2B).Conclusion:In RA, statins moderated the effect of CRP on CVD event risk and new plaque formation in coronary segments without plaque. Longer statin duration was also associated with an increased likelihood of protective calcification of non-calcified plaque.Disclosure of Interests:George Karpouzas Grant/research support from: Pfizer, Consultant of: Sanofi-Genzyme-Regeneron, Janssen, Speakers bureau: Sanofi-Genzyme-Regeneron, BMS, Sarah Ormseth: None declared, Elizabeth Hernandez: None declared, Matthew Budoff: None declared

Physical activity, sedentary behavior, and long-term cardiovascular risk in individuals with rheumatoid arthritis

ABSTRACTObjective: Individuals with rheumatoid arthritis (RA) have increased risk of cardiovascular disease (CVD). Lifestyle factors such as prolonged sedentary behavior (SB) and reduced physical activity (PA) may heighten the risk of CVD. The objective of the study was to investigate the role of SB and PA as predictors for long-term CVD risk in RA patients.Methods: A subsample of 273 people diagnosed with RA was extracted from the 2003–2006 National Health and Nutrition Examination Survey and included in this cross-sectional study. Valid accelerometry data were categorized into sedentary behavior, very light, light, and moderate-to-vigorous physical activity. Functional limitations were assessed using a physical function questionnaire. The Framingham risk score (FRS) was used to calculate 10-year CVD risk. Regression models were used to examine the relationships between SB, PA, and 10-year CVD risk while controlling for potential confounders.Results: Participants spent an average of 9 h/day sedentary, 4 h in very light PA, 1 h in light PA, and 0.4 h in moderate-to-vigorous PA. Greater sedentary time was associated with higher 10-year CVD risk (p= 0.019). Increased daily PA, at all intensities, was inversely associated with 10-year CVD risk (p< 0.01). In the fully adjusted regression model, associations between 10-year CVD risk and SB (β = 0.31, R2 = 0.27, p< 0.01), very light PA (β = −0.19, R2 = 0.26, p< 0.01), light PA (β = −0.16, R2 = 0.25, p< 0.01), and moderate-to-vigorous PA (β = −0.15, R2 = 0.25, p< 0.01) remained significant.Conclusions: Strategies for decreasing SB and increasing PA should be explored with individuals with RA in order to decrease long-term CVD risk.

Comparison of the effects of exercise and anti-TNF treatment on cardiovascular health in rheumatoid arthritis: results from two controlled trials

People with rheumatoid arthritis (RA) are at increased risk for cardiovascular disease (CVD). Both pharmacological treatment and exercise are suggested in the management of CVD risk in RA. This study explored the effects of exercise and anti-TNF treatment on CVD risk in RA. Twenty RA patients (70% female, 50 (10) years) completed a 3-month exercise intervention and 23 RA patients (65% female, 54 (15) years) started anti-TNF treatment. Markers of disease activity, CVD risk, and vascular function were assessed before and after 3-months of intervention/treatment. Both exercise and anti-TNF treatment improved functional ability and fatigue, anti-TNF treatment was more successful in improving inflammation, disease activity, functional ability and pain. Exercise induced a reduction in overall CVD risk and improvement in vascular function, which was significantly different from anti-TNF treatment where no such changes were found. These findings showed that exercise and anti-TNF had differential effects on CVD risk in RA, and should be combined for optimal CVD risk reduction. Whereas anti-TNF treatment is likely to impact on CVD risk through reducing the systemic inflammatory load, exercise should be recommended to people with RA as an effective self-management strategy to reduce CVD risk further. Once RA patients have responded successfully to anti-TNF treatment, increasing exercise should be encouraged to reduce the risk for CVD. Thus, supporting exercise programmes when the disease is controlled, is likely to enhance the uptake and the maintenance of exercise, which will result in additional benefits to cardiovascular health and wellbeing in people with RA.

Is Rheumatoid Arthritis a Cardiovascular Risk-Equivalent to Diabetes Mellitus?

The 2013 American College of Cardiology/American Heart Association cholesterol treatment guidelines recommend statins for patients with diabetes mellitus ages 40-75 years due to their elevated cardiovascular disease (CVD) risk. We compared the incidence of hospitalized acute myocardial infarction (MI), stroke, and coronary revascularization according to whether patients had diabetes mellitus, rheumatoid arthritis (RA), both, or neither. Using 2006-2010 private and public health plan claims, we identified 4 mutually exclusive retrospective cohorts ages >40 years: patients with RA and diabetes mellitus, RA only, diabetes mellitus only, or neither condition. Patients with prevalent CVD were excluded. Outcomes included acute MI and stroke, identified from inpatient discharge diagnosis codes, and coronary revascularization from procedure codes. Across the 4 cohorts, we calculated incidence rates (IRs) of the outcomes, standardized to the 2010 US census age and sex distribution. We identified 920,772 eligible participants. The age- and sex-standardized IRs (per 1,000 person-years) for MI were highest among patients with RA and diabetes mellitus (IR 12.6 [95% confidence interval (95% CI) 10.7-14.7]), followed by patients with diabetes mellitus only (IR 10.7 [95% CI 10.3-11.0]), RA only (IR 5.7 [95% CI 5.2-6.3]), and with neither condition (IR 4.2 [95% CI 4.1-4.3]). Findings from the present study suggest that while CVD risk in RA is elevated, it is lower in magnitude compared to the CVD risk associated with diabetes mellitus. Therefore, considering RA a diabetes mellitus risk-equivalent with respect to hyperlipidemia management may not be appropriate.

Update on Cardiovascular Disease Risk in Patients with Rheumatic Diseases

Cardiovascular disease (CVD) risk is 1.5-fold higher in rheumatoid arthritis (RA), partly due to subclinical atherosclerosis that develops before the diagnosis of RA. Dyslipidemia in RA is better quantified by lipoproteins and apolipoproteins than by cholesterol levels. Current risk factors likely underestimate CVD risk by underestimating prior risk factor levels. Some of the 2-fold higher risk of heart failure and total mortality in RA may be due to myocardial disease caused by inflammation. Per recent recommendations, to reduce CVD risk in RA, control disease activity, reduce inflammation, and aggressively treat CVD risk factors.

Risk of cardiovascular disease in Chinese patients with rheumatoid arthritis: A cross-sectional study based on hospital medical records in 10 years.

ObjectiveThough the risk of cardiovascular disease (CVD) in rheumatoid arthritis (RA) has been established in Western population, little is known about the risk in Chinese people with RA. Our objective was to estimate the risk of CVD in Chinese people with RA using hospital medical records data.MethodsThe inpatients medical record database 2005–2015 of Sichuan provincial people’s hospital was examined. All individuals with a primary diagnosis of RA were included as cases, and those of osteoarthritis (OA) were included as controls, which consisted of the unmatched dataset. Then, RA cases and OA controls were matched by sex and age at 1:1 ratio, forming the matched dataset. The morbidity of CVD (including ischemia heart disease (IHD), congestive heart failure (CHF), et al), stroke and arthrosclerosis were extracted from the database, so as the demographic data and comorbidities related to CVD. Multiple logistic regression analysis was used to estimate the risk of CVD in RA adjusted for demographics and comorbidities using the unmatched dataset. Sensitivity analysis was conducted 1) considering interaction terms between RA and comorbidities, and 2) using multivariable conditional logistic regression for the matched dataset.ResultsThe unmatched dataset comprised of 1824RA cases and 1995 OA controls and the matched dataset comprised of 1022 pairs of sex and age matched RA and OA patients. RA exhibited increased odds of prevalent CVD compared with OA, and the adjusted ORs (95%CIs) for CVD, stroke, IHD, CHF, and atherosclerosis were1.86(1.42–2.43), 1.11(0.71–1.74), 1.47(0.97–2.24), 2.09(1.03–4.22), and 2.49 (1.97–3.13), respectively, and was 2.26 (1.29–3.96)for IHD further adjusted for interaction term. The matched dataset analysis found similar results.ConclusionsChinese people with RA were approximated 2 times more likely to have CVD, IHD, CHF and atherosclerosis compared with those with OA. The findings justified the need of further longitudinal study to establish the causal-relationship between RA and CVD and to estimate the precise risk in this population.

Cardiovascular Risk Factors and Disease Characteristics Are Consistently Associated with Arterial Function in Rheumatoid Arthritis.

Arterial properties influence cardiovascular disease (CVD) risk. We identified potential determinants of arterial function in patients with rheumatoid arthritis (RA). Relationships of traditional cardiovascular risk factors and RA characteristics with arterial stiffness (pulse wave velocity), wave reflection (augmentation index, reflected wave pressure, and reflection magnitude), and pressure pulsatility (central systolic and pulse pressure, peripheral pulse pressure, pulse pressure amplification, and forward wave pressure) were identified in multivariable backward regression models among 177 patients without established CVD (118 white, 32 Asian, 22 black, 5 mixed ancestry). Recorded characteristics explained 37% (pulse wave velocity) to 71% (reflected wave pressure) of the variability in arterial function. These factors were particularly associated with wave reflection and pressure pulsatility: RA duration (p = 0.04), rheumatoid factor status (p = 0.01 to 0.03), leukocyte counts (p = 0.02 to 0.05), and total cholesterol (p < 0.01 to 0.03). Body mass index (p < 0.01 to 0.02) and insulin resistance (p < 0.01 to 0.01) were related to reduced wave reflection and peripheral pulse pressure. Exercise (p = 0.02) and alcohol consumption (p < 0.01) were associated with increased pulse pressure amplification and decreased peripheral pulse pressure, respectively. Tumor necrosis factor-α inhibition (p < 0.01) was related to reduced pulse wave velocity, and tetracycline use (p = 0.02) to decreased peripheral pulse pressure. Traditional cardiovascular risk factors and disease characteristics are consistently associated with vascular hemodynamic alterations in RA. The relative effect of arterial stiffness, wave reflection, and pressure pulsatility on CVD risk in RA needs further study.

Managing Cardiovascular Disease Risk in Rheumatoid Arthritis: Clinical Updates and Three Strategic Approaches.

By critically reviewing literature published within the past 5years, we aim to clarify current knowledge and gaps regarding CVD risk management in RA. We examine recent guidelines, recommendations, and evidence and discuss three approaches: (1) RA-specific management including treat-to-target and medication management, (2) assessment of comprehensive individual risk, and (3) targeting traditional CVD risk factors (hypertension, smoking, hyperlipidemia, diabetes, obesity, and physical inactivity) at a population level. Considering that 75% of US RA visits occur in specialty clinics, further research is needed regarding evidence-based strategies to manage and reduce CVD risk in RA. This review highlights clinical updates including US cardiology and international professional society guidelines, successful evidence-based population approaches from primary care, and novel opportunities in rheumatology care to reduce CVD risk in RA.

Risk factors for the rapid increase in risk of acute coronary events in patients with new-onset rheumatoid arthritis: a nested case-control study.

To investigate risk factors for acute coronary syndrome (ACS) in patients with new-onset rheumatoid arthritis (RA). We performed a nested case-control study of patients with incident RA included in the Epidemiological Investigation of RA study. Cases with ACS were identified using Swedish national health registers and matched with up to 5 controls without ACS, based on incidence density-based sampling. Information on potential exposures (clinical disease activity, serologic features, genetic markers, comorbidities, pharmacotherapies, and sick leave) was collected from medical charts and register-based sources. We identified 138 cases and 624 controls. Smoking, history of myocardial infarction, and >50 days of sick leave the year following RA onset were associated with an increased risk of ACS. Area under the curve measurements of C-reactive protein level, erythrocyte sedimentation rate, Disease Activity Score in 28 joints (DAS28), and global health in the upper tertile during the first year and the complete followup period were both strongly associated with an increased risk of ACS. Treatment with disease-modifying antirheumatic drugs did not alter the ACS risk, nor did the presence of rheumatoid factor (RF) or shared epitope alleles, whereas high anti-citrullinated protein antibody (ACPA) levels were borderline significantly associated with ACS risk. In this study of risk factors for ACS in incident RA, clinical markers of inflammatory activity, disease activity, and total number of days of sick leave and disability pension during the first year following RA onset were identified as ACS risk factors. We found no association with RF, which was previously linked to cardiovascular disease risk in RA, but there was a borderline significant association with high ACPA levels.

Abstract 46: Cellular Cholesterol Homeostasis is Altered in Murine Models of Rheumatoid Arthritis and is Linked to Enhanced Myelopoiesis

Rheumatoid arthritis (RA) is associated with a ~2-fold elevated risk of morbidity and mortality from atherosclerotic cardiovascular disease (CVD) compared with the general population. Atherosclerosis in RA patients tends to be more aggressive and therefore more challenging to treat. Identifying CVD in these patients is difficult as traditional CVD risk factors, such as changes in plasma lipid profiles (i.e. elevated LDL, decreased HDL) are not always observed, underscoring the need for better understanding of the reasons contributing to the enhanced atherosclerosis in RA patients. People with RA often have monocytosis and neutrophilia, which we hypothesize to plays causal roles in atherosclerosis. Two mouse models of RA were used, K/BxN serum transfer and collagen induced arthritis (CIA). Flow cytometry was used to quantify the abundance of leukocyte and stem cell subsets. BODIPY-cholesterol was employed to determine the membrane cholesterol status of the various cells. Prominent monocytosis and neutrophilia due to an expansion and increased proliferation of the haematopoietic stem and multipotential progenitor cells (HSPCs) in the bone marrow (BM) was observed in both models of RA. There was also an increase in the mobilisation of HSPCs into the circulation, which homed to the spleen, resulting in extramedullary haematopoiesis. Interestingly, key cholesterol efflux genes, Abca1, Abcg1 and Apoe were down regulated in the BM HSPCs isolated from the K/BxN mice, resulting in increased cell membrane cholesterol levels. We also observed an increase in the expression of the common beta subunit of the interlukin-3 receptor on the HSPCs and the M-CSF receptor in myeloid progenitor cells, likely explaining their increased proliferation and skewing to the myeloid lineage. Moreover, blood monocytes and neutrophils had increased membrane cholesterol content, independent of changes in plasma cholesterol levels. These data suggest that while plasma cholesterol levels may not be increased in RA, cellular cholesterol homeostasis might be increased. We hypothesize that this, together with enhanced monocyte production, underlies the increased risk of CVD in RA.

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...