Cardiovascular Risk in Rheumatoid Arthritis and Mechanistic Links: From Pathophysiology to Treatment

2020 ◽  
Vol 18 (5) ◽  
pp. 431-446 ◽  
Author(s):  
George E. Fragoulis ◽  
Ismini Panayotidis ◽  
Elena Nikiphorou
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Current Evidence ◽  
Pharmacological Intervention ◽  
Cvd Risk ◽  
The Past ◽  
Increased Risk ◽  
Cv Disease ◽  
Obesity Hypertension ◽  
Inflammatory Burden

Rheumatoid arthritis (RA) is an autoimmune inflammatory arthritis. Inflammation, however, can spread beyond the joints to involve other organs. During the past few years, it has been well recognized that RA associates with increased risk for cardiovascular (CV) disease (CVD) compared with the general population. This seems to be due not only to the increased occurrence in RA of classical CVD risk factors and comorbidities like smoking, obesity, hypertension, diabetes, metabolic syndrome, and others but also to the inflammatory burden that RA itself carries. This is not unexpected given the strong links between inflammation and atherosclerosis and CVD. It has been shown that inflammatory cytokines which are present in abundance in RA play a significant role in every step of plaque formation and rupture. Most of the therapeutic regimes used in RA treatment seem to offer significant benefits to that end. However, more studies are needed to clarify the effect of these drugs on various parameters, including the lipid profile. Of note, although pharmacological intervention significantly helps reduce the inflammatory burden and therefore the CVD risk, control of the so-called classical risk factors is equally important. Herein, we review the current evidence for the underlying pathogenic mechanisms linking inflammation with CVD in the context of RA and reflect on the possible impact of treatments used in RA.

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

2021 ◽  
Vol 14 ◽  
pp. 117954412110287
Author(s):  
Mir Sohail Fazeli ◽  
Vadim Khaychuk ◽  
Keith Wittstock ◽  
Boris Breznen ◽  
Grace Crocket ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Cardiovascular Disease ◽  
Literature Review ◽  
Rheumatoid Factor ◽  
Qualitative Evidence Synthesis ◽  
Cvd Risk ◽  
Rheumatoid Arthritis Risk ◽  
Published Evidence ◽  
Increased Risk

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.

Assessment of microalbuminuria and ankle-brachial index in outpatients with schizophrenia treated with antipsychotics - a possible predictors of cardiovascular disease

2011 ◽  
Vol 26 (S2) ◽  
pp. 1436-1436
Author(s):  
R. Malý ◽  
D. Kalnická ◽  
J. Masopust ◽  
K. Minářová ◽  
M. Vašatová ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ankle Brachial Index ◽  
Systolic Pressure ◽  
Framingham Risk ◽  
Excess Morbidity ◽  
Increased Risk ◽  
Artery Disease ◽  
Glucose Tolerance Status ◽  
Cv Disease ◽  
Obesity Hypertension

Schizophrenia and related psychoses are associated with excess morbidity and mortality from cardiovascular (CV) disease. Microalbuminuria (MA) is associated with an increased risk of CV disease and mortality. This association is independent of other known CV risk factors such as hypertension, dyslipidemia, obesity, smoking, and impaired renal function. The ankle brachial index (ABI), which is the ratio of systolic pressure at the ankle to that in the arm, is quick and easy to measure and has been used to confirm the diagnosis and assess the severity of peripheral artery disease. Low ABI has been related to an increased incidence of total and CV mortality and CV events. The objective of prospective pilot study was to determine MA and ABI as well as the prevalence of CV risk factors (glucose tolerance status, lipids levels, obesity, hypertension, smoking) and assessment of Framingham risk score in patients with schizophrenia treated with antipsychotic drugs. The study included thirty-three outpatient subjects (female, n = 16), aged 21–66 years. The exclusion criteria included urinary infection and presence of diabetes mellitus. Three patients (7,7%) has abnormal (>26 mg/d) levels of MA, non of ABI.In conclusion, stratification by MA can help identify a high-risk subset of nondiabetic patients with schizophrenia in risk of CV events.

scholarly journals Rheumatoid arthritis: influence of inflammation and anti-inflammatory therapy on cardiovascular risk factors

2020 ◽  
pp. 32-44
Author(s):  
D. I. Trukhan ◽  
D. S. Ivanova ◽  
K. D. Belus
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Cardiovascular Risk ◽  
Cardiovascular Diseases ◽  
Cardiovascular Risk Factors ◽  
Chronic Inflammation ◽  
Pharmacological Intervention ◽  
Increased Risk ◽  
Inflammatory Drugs ◽  
Anti Inflammatory

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.

scholarly journals Cardiovascular Event Risk in Rheumatoid Arthritis Compared with Type 2 Diabetes: A 15-year Longitudinal Study

2019 ◽  
Vol 47 (3) ◽  
pp. 316-324 ◽  
Author(s):  
Rabia Agca ◽  
Luuk H.G.A. Hopman ◽  
Koen J.C. Laan ◽  
Vokko P. van Halm ◽  
Mike J.L. Peters ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Type 2 Diabetes ◽  
Incidence Rate ◽  
Cvd Risk ◽  
Cardiovascular Research ◽  
Number Of Patients ◽  
Cv Disease ◽  
Reference Cohort

Objective.Cardiovascular (CV) disease (CVD) risk is increased in rheumatoid arthritis (RA). However, longterm followup studies investigating this risk are scarce.Methods.The CARRÉ (CARdiovascular research and RhEumatoid arthritis) study is a prospective cohort study investigating CVD and its risk factors in 353 patients with longstanding RA. CV endpoints were assessed at baseline and 3, 10, and 15 years after the start of the study and are compared to a reference cohort (n = 2540), including a large number of patients with type 2 diabetes (DM).Results.Ninety-five patients with RA developed a CV event over 2973 person-years, resulting in an incidence rate of 3.20 per 100 person-years. Two hundred fifty-seven CV events were reported in the reference cohort during 18,874 person-years, resulting in an incidence rate of 1.36 per 100 person-years. Age- and sex-adjusted HR for CV events were increased for RA (HR 2.07, 95% CI 1.57–2.72, p < 0.01) and DM (HR 1.51, 95% CI 1.02–2.22, p = 0.04) compared to the nondiabetic participants. HR was still increased in RA (HR 1.82, 95% CI 1.32–2.50, p < 0.01) after additional adjustment for CV risk factors. Patients with both RA and DM or insulin resistance had the highest HR for developing CVD (2.21, 95% CI 1.01–4.80, p = 0.046 and 2.67, 95% CI 1.30–5.46, p < 0.01, respectively).Conclusion.The incidence rate of CV events in established RA was more than double that of the general population. Patients with RA have an even higher risk of CVD than patients with DM. This risk remained after adjustment for traditional CV risk factors, suggesting that systemic inflammation is an independent contributor to CV risk.

scholarly journals Role of Testosterone in the Treatment of Cardiovascular Disease

2017 ◽  
Vol 12 (02) ◽  
pp. 1 ◽  
Author(s):  
Carolyn M Webb ◽  
Peter Collins ◽  
◽  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Cardiovascular System ◽  
Serum Testosterone ◽  
Current Evidence ◽  
Premature Coronary Artery Disease ◽  
Cvd Risk ◽  
Testosterone Levels ◽  
Increased Risk

Cardiovascular disease (CVD) is the most prevalent non-communicable cause of death worldwide. Testosterone is a sex hormone that is predominant in males but also occurs in lower concentrations in females. It has effects directly on the blood vessels of the cardiovascular system and on the heart, as well as effects on risk factors for CVD. Serum testosterone concentrations are known to decrease with age and reduced testosterone levels are linked to premature coronary artery disease, unfavourable effects on CVD risk factors and increased risk of cardiovascular mortality independent of age. A significant number of men with heart failure demonstrate reduced serum testosterone concentrations and there is early evidence suggesting that low testosterone levels affect cardiac repolarisation. Any association between endogenous testosterone concentrations and CVD in women has yet to be established. Testosterone replacement is used to treat men with hypogonadism but also has cardiovascular effects. This review will present the current evidence, expert opinion and controversies around the role of testosterone in the pathophysiology of CVD and surrounding the use of testosterone treatment and its effects on the cardiovascular system and CVD.

scholarly journals Effects of a 12-week cardiovascular rehabilitation programme on systemic inflammation and traditional coronary artery disease risk factors in patients with rheumatoid arthritis (CARDIA trial): a randomised controlled trial

BMJ Open ◽  
2017 ◽  
Vol 7 (12) ◽  
pp. e018540
Author(s):  
Stefan Heinze-Milne ◽  
Volodko Bakowsky ◽  
Nicholas Giacomantonio ◽  
Scott A Grandy
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Heart Rate ◽  
Randomised Controlled Trial ◽  
Systemic Inflammation ◽  
Controlled Trial ◽  
Disease Assessment ◽  
Cvd Risk ◽  
Increased Risk ◽  
Randomised Controlled

IntroductionPatients with systemic inflammatory diseases such as rheumatoid arthritis (RA) have an increased risk of cardiovascular disease (CVD) above the baseline risk attributable to traditional CVD risk factors seen in the general population. Exercise in cardiac rehabilitation (CR) is designed specifically for high-risk primary prevention and those with established CVD. Even though the European League Against Rheumatism guidelines state that exercise is safe for individuals with RA and exercise can reduce CVD risk, patients with RA rarely participate in CR. Thus, little is known about CR’s impact on inflammatory and CVD risk in the RA population. The purpose of this trial is to determine the feasibility of a 12-week CR programme for patients with RA and whether it decreases CVD risk without exacerbating RA.Methods and analysisThis is a randomised controlled trial whereby 60 participants with RA will be recruited and randomly assigned to either standard of care (SOC) treatment or SOC plus a 12-week CR programme (60 min of education plus two 60 min aerobic exercise sessions/week). Exercise will be performed at 60%–80% of heart rate reserve. Outcome measures (Framingham Risk Score, resting heart rate, blood pressure, blood lipids, markers of systemic inflammation (ie, interleukin (IL) 6 and tumour necrosis factor-α (TNF-α), Clinical Disease Assessment Index, Disease Activity Score-28, physical activity levels and peak cardiorespiratory fitness) will be assessed preintervention (week-0), postintervention (week-13) and 6 months postintervention.Ethics and disseminationEthical approval was obtained from the Nova Scotia Health Authority Research Ethics Board. Results will be submitted for publication in an appropriate peer-reviewed journal.Trial registration numberNCT01534871; Pre-results

Effect of a treat-to-target intervention of cardiovascular risk factors on subclinical and clinical atherosclerosis in rheumatoid arthritis: a randomised clinical trial

2019 ◽  
pp. annrheumdis-2018-214075 ◽  
Author(s):  
Benjamin Burggraaf ◽  
Deborah F van Breukelen-van der Stoep ◽  
Marijke A de Vries ◽  
Boudewijn Klop ◽  
Anho H Liem ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Usual Care ◽  
Cardiovascular Events ◽  
Target Group ◽  
Secondary Outcome ◽  
Treat To Target ◽  
Cvd Risk Factors ◽  
Cvd Risk ◽  
Increased Risk

BackgroundPatients with rheumatoid arthritis (RA) have an increased risk for cardiovascular disease (CVD). No long-term intervention trials on CVD risk factors have been published, and a debate on the efficacy of controlling traditional risk factors in RA is ongoing. We aimed to evaluate a treat-to-target approach versus usual care regarding traditional CVD risk factors in patients with RA.MethodsIn this open-label, randomised controlled trial, patients with RA aged <70 years without prior CVD or diabetes mellitus were randomised 1:1 to either a treat-to-target approach or usual care of traditional CVD risk factors. The primary outcome was defined as change in carotid intima media thickness (cIMT) over 5 years, and the secondary outcome was a composite of first occurrence of fatal and non-fatal cardiovascular events.ResultsA total of 320 patients (mean age 52.4 years; 69.7% female) with RA underwent randomisation and 219 patients (68.4%) completed 5 years of follow-up. The mean cIMT progression was significantly reduced in the treat-to-target group compared with usual care (0.023 [95% CI 0.011 to 0.036] mm vs 0.045 [95% CI 0.030 to 0.059] mm; p=0.028). Cardiovascular events occurred in 2 (1.3%) of the patients in the treat-to-target group vs 7 (4.7%) in those receiving usual care (p=0.048 by log-rank test).ConclusionThis study provides evidence on the benefit of a treat-to-target approach of traditional CVD risk factors for primary prevention in patients with well-treated RA.Trial registration numberNTR3873.

Abstract 13659: Development of a TransAtlantic Cardiovascular risk Calculator for Rheumatoid Arthritis (ATACC-RA)

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Anne Grete Semb ◽  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
External Validation ◽  
Model Performance ◽  
Density Lipoprotein ◽  
Risk Calculator ◽  
Cvd Risk ◽  
Cox Models ◽  
C Statistic ◽  
Increased Risk

Introduction: Patients with rheumatoid arthritis (RA) have an increased risk of cardiovascular disease (CVD), which is not accurately predicted by risk calculators designed for the general population. Hypothesis: To develop a RA specific CVD risk calculator. Methods: The study population included RA patient cohorts from 8 centres in 7 countries. In all cases, data had been collected prospectively on CV outcomes (MI, revascularization, angina, stroke, TIA, PAD and CV death). At baseline RA characteristics (duration, seropositivity, disease activity (DAS28) and CRP/ESR) were collected in addition to traditional CV risk factors. Cox models stratified by centre were used to develop a CVD risk calculator considering traditional CV risk factors and RA characteristics. Model performance was assessed using measures of discrimination and calibration. Results: In total 3176 RA patients who did not have prior CVD were included (mean age: 55 [SD: 14] years, 73% female). During a mean follow-up of 7.8 years (24733 person years), 314 had a CVD event. The multivariable risk score modelling revealed 2 models including either seropositivity or DAS28 along with age, sex, current smoking, presence of hypertension, and ratio of total cholesterol to high-density lipoprotein (table). Both 10-fold cross validation and multiple imputation analyses confirmed these findings with little change to the estimated coefficients. Both models demonstrated good discrimination (c-statistic: 0.76 and 0.74) and calibration (observed/predicted ratio: 1.00; 95% confidence interval: 0.89, 1.12). The ATACC-RA (mean: 11.5%, SD 14.1%) showed significantly improved discrimination compared to either Framingham (c-statistic: 0.71, p<0.001) or SCORE (c-statistic: 0.72, p<0.001) risk algorithms. Conclusions: Development of an RA-specific CVD risk calculator is feasible by pooling resources from many centres. Further development including external validation is underway.

scholarly journals Fragility Fractures Are Associated with an Increased Risk for Cardiovascular Events in Women and Men with Rheumatoid Arthritis: A Population-based Study

2017 ◽  
Vol 44 (5) ◽  
pp. 558-564 ◽  
Author(s):  
Orla Ni Mhuircheartaigh ◽  
Cynthia S. Crowson ◽  
Sherine E. Gabriel ◽  
Veronique L. Roger ◽  
L. Joseph Melton ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Fragility Fracture ◽  
Fragility Fractures ◽  
Population Based ◽  
Cvd Risk ◽  
Cox Models ◽  
Excess Morbidity ◽  
Increased Risk ◽  
Time Dependent Covariates

Objective.Women and men with rheumatoid arthritis (RA) have an increased risk for fragility fractures and cardiovascular disease (CVD), each of which has been reported to contribute to excess morbidity and mortality in these patients. Fragility fractures share similar risk factors for CVD but may occur at relatively younger ages in patients with RA. We aimed to determine whether a fragility fracture predicts the development of CVD in women and men with RA.Methods.We studied a population-based cohort with incident RA from 1955 to 2007 and compared it with age- and sex-matched non-RA subjects. We identified fragility fractures and CVD events following the RA incidence/index date, along with relevant risk factors. We used Cox models to examine the association between fractures and the development of CVD, in which fractures and CVD risk factors were modeled as time-dependent covariates.Results.There were 1171 subjects (822 women; 349 men) in each of the RA and non-RA cohorts. Over followup, there were 406 and 346 fragility fractures and 286 and 225 CVD events, respectively. The overall CVD risk was increased significantly for RA subjects following a fragility fracture (HR 1.81, 95% CI 1.38–2.37) but not for non-RA subjects (HR 1.18, 95% CI 0.85–1.63). Results were similar for women and men with RA.Conclusion.Fragility fractures in both women and men with RA are associated with an increased risk for CVD events and should raise an alert to clinicians to target these individuals for further screening and preventive strategies for CVD.

scholarly journals POS0096 SPLENIC METABOLIC UPTAKE IN FDG-PET/CT PREDICTS RISK OF FUTURE CARDIOVASCULAR THROMBOSIS EVENTS IN PATIENTS WITH RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 258.2-259
Author(s):  
S. J. Lee ◽  
C. M. Hong ◽  
Y. M. Kang
Keyword(s):  
Rheumatoid Arthritis ◽  
Risk Factors ◽  
Disease Activity ◽  
Fdg Pet ◽  
Cvd Risk ◽  
Positron Emission ◽  
Increased Risk ◽  
Pet Ct ◽  
Fdg Pet Ct

Background:Patients with the rheumatoid arthritis (RA) have an increased risk of cardiovascular disease (CVD) compared to general population. However there are insufficient modality to predict future CVD risk in RA.Objectives:This study assessed whether splenic and arterial activity measured by positron emission tomography/ computed tomography (PET/CT) predict the risk of CVD thrombosis events beyond conventional risk factors in patients with RA.Methods:We enrolled 84 patients with active RA who underwent fluorine-18-fluorodeoxyglucose (FDG) PET/CT and disease activity evaluation at the same time. CVD thrombosis events were independently evaluated, while blinded to activity of PET/CT, during follow up periods. FDG uptake by nuclear medicine physician was examined in the spleen and ascending aorta and blood pool activity of superior vena cava as SUV (standardized uptake values) and target-to-background-ratio (TBR) while blinded to CVD events.Results:During follow-up periods, 19 patients developed CVD thrombosis events. Both splenic and arterial TBR were significantly increased in patients with subsequent CVD events compared to in patients without (2.19 ± 0.60 vs 1.80 ± 0.34, p < 0.013, 1.72 ± 0.22 vs 1.57 ± 0.22, p< 0.012). Splenic TBR was associated with an increased risk of CVD events after adjustment for conventional CVD risk factors [hazard ratio (HR): 3.15; 95% confidence interval (CI): 1.46 to 6.79; p = 0.003]. Moreover, the association between splenic TBR and CVD events remained significant after adjustment for disease activity (HR: 3.00; CI: 1.36 to 6.63; p = 0.007) and after adjustment for arterial TBR (HR: 3.00; CI: 1.36 to 6.63; p = 0.007).Conclusion:Our results show splenic metabolic uptake in FDG-PET/CT in patients with RA provide information for subsequent CVD events beyond conventional risk factors.References:[1]Lee SJ, Jeong JH, Lee CH, et al. Development and validation of an (18) F-fluorodeoxyglucose-positron emission tomography with computed tomography-based tool for the evaluation of joint counts and disease activity in patients with rheumatoid arthritis. Arthritis Rheumatol. 2019;71:1232-1240.Disclosure of Interests: :None declared

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