Cardiovascular Disease In Rheumatoid Arthritis Patients Research Articles

Actual and Perceived Risk of Cardiovascular Disease among Sample of Iraqi Patients with Rheumatoid Arthritis

Background: Independent of conventional risk factors, patients with rheumatoid arthritis (RA) have a significantly increased risk of cardiovascular disease (CVD). Aims of the study: To evaluate the actual and perceived 10-year CVD risk among Iraqi patients with RA as well as their level of knowledge about CVD risk. Patients and methods: This cross-sectional study included 100 RA patients (85 females and 15 males) who visited Baghdad Teaching Hospital/Rheumatology Unit from January 2021 till July 2021. The Framingham Risk Score (FRS) was used to calculate the actual 10-year risk of CVD. The Heart Disease Fact-Rheumatoid Arthritis Questionnaire (HDFQ-RA) was used to assess the subjects’ cardiovascular disease knowledge. Results: Among a hundred Iraqi patients with RA, the median age was 51.23 ± 8.4 years. The findings of the study revealed that 23% had high risk for CVD and 27% & 50% had moderate and low risk respectively based on FRS calculator. The risk of CVD was significantly affected by the age of disease onset and seropositivity and steroid use (p value 0.001). When the perceived risk was compared to the actual risk of cardiovascular disease, there was a weak agreement between them, only 31% had corresponding answers. Conclusions: The study showed an elevated risk of CVD in rheumatoid arthritis patients, as well as a gap between actual and perceived CVD risk.

Actual and Perceived Risk of Cardiovascular Disease among Sample of Iraqi Patients with Rheumatoid Arthritis

Background: Independent of conventional risk factors, patients with rheumatoid arthritis (RA) have a significantly increased risk of cardiovascular disease (CVD). Aims of the Study: To evaluate the actual and perceived 10-year CVD risk among Iraqi patients with RA as well as their level of knowledge about CVD risk. Patients and methods: This cross-sectional study included 100 RA patients (85 females and 15 males) who visited Baghdad Teaching Hospital/Rheumatology Unit from January 2021 to July 2021. The Framingham Risk Score (FRS) was used to calculate the actual 10-year risk of CVD. The Heart Disease Fact-Rheumatoid Arthritis Questionnaire (HDFQ-RA) was used to assess the subjects' knowledge of cardiovascular disease. Results: Among hundred Iraqi patients with RA, the median age was 51.23 8.4 years. The study's findings revealed that 23% had a high risk for CVD and 27% & 50% had moderate and low risk, respectively, based on the FRS calculator. The risk of CVD was significantly affected by the age of disease onset and seropositivity and steroid use (p-value 0.001). When the perceived risk was compared to the actual risk of cardiovascular disease, there was a weak agreement between them; only 31% had corresponding answers. Conclusions: The study showed an elevated risk of CVD in rheumatoid arthritis patients and a gap between actual and perceived CVD risk.

Prevalence of cardiovascular diseases and traditional cardiovascular risk factors in patients with rheumatoid arthritis: a real-life evidence from BioSTAR nationwide registry.

Patients with rheumatoid arthritis (RA) have increased morbidity and mortality due to cardiovascular (CV) comorbidities. The association of CV diseases (CVD) and traditional CV risk factors has been debated, depending on patient and RA characteristics. This study aimed to find the prevalence of CVD and CV risk factors in patients with RA. A multi-center cross-sectional study was performed on RA patients using the BioSTAR (Biological and Targeted Synthetic Disease-Modifying Antirheumatic Drugs Registry) in September 2022. Socio-demographic, clinical, and follow-up data were collected. Myocardial infarction, ischemic heart disease, peripheral vascular disorders, congestive heart failure, ischemic stroke, and transient ischemic attack were regarded as major adverse cardiovascular events (MACEs). CVD was defined as the presence of at least one clinical situation of MACE. Group 1 and Group 2 included patients with and without CVD. Prevalence rates of CVD and traditional CV risk factors were the primary outcomes. Secondary outcomes were the differences in the clinical characteristics between patients with and without CVD. An analysis of 724 patients with a mean age of 55.1 ± 12.8years diagnosed with RA was conducted. There was a female preponderance (79.6%). The prevalence rate of CVD was 4.6% (n = 33). The frequencies of the diseases in the MACE category were ischemic heart disease in 27, congestive heart failure in five, peripheral vascular disorders in three, and cerebrovascular events in three patients. The patients with CVD (Group 1) were significantly male, older, and had higher BMI (p = 0.027, p < 0.001, and p = 0.041). Obesity (33.4%) and hypertension (27.2%) were the two CV risk factors most frequently. Male sex (HR = 7.818, 95% CI 3.030-20.173, p < 0.001) and hypertension (HR = 4.570, 95% CI 1.567-13.328, p = 0.005) were the independent risk factors for CVD. The prevalence of CVD in RA patients was 4.6%. Some common risk factors for CVD in the general population, including male sex, older age, and hypertension, were evident in RA patients. Male sex and hypertension were the independent risk factors for developing CVD in patients with RA.

Meta-analysis of risk factors for cardiovascular disease in patients with rheumatoid arthritis.

Cardiovascular disease (CVD) is a common complication of rheumatoid arthritis (RA). We aimed to explore the risk factors for cardiovascular disease in patients with rheumatoid arthritis and provide a scientific basis on effective prevention and treatments for CVD in RA patients. We searched for a combination of the subject words and free words involved arthritis, rheumatoid, CVD, heart disease, vascular disease, risk factors, etc. from China Knowledge Network, Wanfang, Vip, China Biomedical Literature Database, Pubmed, Embase, Web of Science, Cochrane and other databases for documents published in public in 2000-October 2022.RevMan 5.3 and Stata14.0 analysis software was used to perform a meta-analysis of case-control and cohort studies on risk factors of CVDs in patients with RA published from 2000 to 2022.The Egger method was used to determine whether there was publication bias. Seventeen pieces of literature were included in this meta-analysis. We explored the associations between CVD and different clinical characters such as DAS28 score, rheumatoid factor, triglyceride, age, sex, C-reactive protein, total cholesterol (TC), hypertension, and D dimer. High serum levels of C-reactive protein, TC, and D-dimer, as well as hypertension, are the main risk factors for CVD in patients with RA. The OR and 95% CI of C-reactive protein were 2.06 (1.91-2.23), RR and 95% CI of TC were 1.7 (1.49-1.93), RR and 95% CI of hypertension were 3.58 (2.37-5.40), as well as OR and 95% CI of D dimer were 2.83 (1.48-5.40).Our results performed by the meta-analysis were reliable, with low publication bias existed. C-reactive protein, TC, hypertension, and D dimer are the main risk factors for CVD in patients with RA. No protective factors were found.

Evaluation of CXCL2 and autophagy genes expression in rheumatoid arthritis patients and its relation to cardiovascular diseases

Background Cardiovascular disease (CVD) is among the most common comorbidity and the leading cause of mortality in rheumatoid arthritis (RA) patients. The aim of this study was to assess at the levels of CXCL2 and autophagy genes such LC3 and Beclin 1 in RA patients and how they relate to the clinical manifestations and carotid intimal medial thickness. Methods This cross-sectional study included RA patients. Sociodemographic characteristics, clinical and therapeutic data were recorded. Thorough medical and clinical examination was conducted to evaluate the disease status including the number of swollen and tender joints, visual analogue scale and disease activity score 28 (DAS28).About 5ml of whole blood was collected from each subject and CXCL2, LC3 and Beclin-1 expression levels were evaluated. The carotid intima-media thickness (CIMT) was assessed by a duplex ultrasound system. As a control group, 79 healthy individuals of matching age and gender were included. Results Seventy-nine patients with RA were included in the study with mean age 45.24 years with (SD=10.07 years). Most of them were females (87.3%) and the median duration of RA was 7 years. Approximately 85% had positive RF, while 70.9% had positive Anti CCP antibody. CXCL2 and LC3 had a statistically significant positive correlation of medium strength (P = 0.026). CXCL2 showed significant positive correlation with presence of subcutaneous rheumatoid nodules while there was a positive correlation of low strength between CXCL2 and systolic BP, diastolic BP and HAQ score. For LC3 gene expression, it was significantly correlated positively with presence of joint deformities, negatively with hypercholesteremia. There was a statistically significant positive correlation of medium strength between LC3 and CIMT in those with disease duration ≥7 years after controlling (adjusting) for patient’s age. Conclusions CXCL2 and autophagy gene expression levels (LC3 and beclin1) are positively correlated with the clinical manifestations and CIMT in RA patients. These genes may serve as predictors for CVD in RA patients.

Increased Risk of Cardiovascular Diseases in Rheumatoid Arthritis: A Systematic Review.

Rheumatoid arthritis (RA) is an autoimmune condition in which the body's jointsare attacked by the immune system, leaving the patient disabled in severe cases, with irreversible joint damageand a lower quality of life. RA patients are more likely to develop cardiovascular (CV) disease, which increases their risk of morbidity and mortality. This study systematically reviews various CV diseases that might occur with RA including heart failure (HF), coronary artery disease, acute coronary syndrome, ischemic heart disease, stroke, cardiac death, venous thromboembolism, and valvular diseases. The relation between these complications and RA is specifically assessed. Systematic search was carried out on literature reporting the risk of each of the CV diseases in RA patients from databases in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The databases searched were MEDLINE(through PubMed) and Google Scholar usinga combination of keywords and medical subject headings (MeSH). Our keywords were mainly "cardiovascular diseases" and "arthritis and rheumatoid". We found a total of 33articles reporting each CV comorbidity. Interestingly, a wide spectrum of CV diseases is reported in patients with RA. Many tools were implemented in the diagnosis of each disease such as carotid intima-media thickness for atherosclerosis and echocardiography for HF. We confirmed that RA is associated with an increased risk of different CV events, and prophylactic measures should be implemented.

Prevalence and influence of hypouricemia on cardiovascular diseases in patients with rheumatoid arthritis

BackgroundSerum uric acid (SUA) acts as an antioxidant and abnormally low SUA may raise the risk of developing atherosclerotic disorders. There is a U-shaped association between SUA with cardiovascular diseases (CVDs) in general population. However, the prevalence of hypouricemia and its influence on CVDs in rheumatoid arthritis (RA) remains unclear.MethodsThis cross-sectional study collected clinical data from a Chinese RA cohort. Hypouricemia was defined as SUA ≤ 3.0 mg/dL, and hyperuricemia was defined as SUA ≥ 7.0 mg/dL. CVDs were defined as a history of angina pectoris, myocardial infarction, heart failure, stroke and peripheral arterial disease. Restricted cubic spline regression and logistic regression analysis were conducted to evaluate the associations between SUA levels and CVDs.ResultsAmong 1130 RA patients recruited, the mean age was 53.2 years and 79.0% were female. The prevalence of hypouricemia and hyperuricemia were 10.6% and 12.0%, respectively. RA patients with hyperuricemia had a higher rate of CVDs than normouricemic patients (27.9% vs. 7.1%, P < 0.05). Surprisingly, RA patients with hypouricemia also had a higher rate of CVDs (20.7% vs. 7.1%, P < 0.05) even without higher traditional cardiovascular risk factors. A U-shaped association between SUA levels and total CVDs was found (Pnon-linear < 0.001). Multivariate logistic regression analysis revealed that compared with normouricemia, both hypouricemia [adjusted OR (AOR) = 4.707, 95% CI 2.570–8.620] and hyperuricemia (AOR = 3.707, 95% CI 2.174–6.321) were associated with higher risk of CVDs.ConclusionsHypouricemia may be a potential risk factor of CVDs in RA patients

Augmentation index, but not pulse wave velocity, is associated with disease activity in rheumatoid arthritis

Rheumatoid arthritis (RA) is associated with premature atherosclerosis and increased risk of cardiovascular disease (CVD). The purpose of this study was to assess the relationship between disease activity and arterial stiffness indexes for CVD in RA patients. Two hundred twenty-two female RA patients were retrospectively recruited. Non-invasive arterial stiffness was assessed by brachial-ankle PWV (baPWV) and ankle-brachial index (ABI) using pulse wave analyses and the augmentation index (AIx). The AIx was classified into two groups of normal (grade 0) and abnormal (grade 1, 2, and 3). The baPWV was associated with only age and rheumatoid factor titer, but not disease activity index, DAS28-ESR. Univariate analysis indicated that AIx was related to body mass index, disease duration, and DAS28-ESR. In addition, the baPWV was associated with DAS28-ESR and disease duration after adjusting for confounding factors (β = 0.147, p = 0.032 and β = 0.183, p = 0.034, respectively). Multivariate logistic regression analysis showed that the tendency for abnormal AIx increased as DAS28-ESR increased, and the result was significant ( p for trend = 0.026). The results of this study indicated that the relationship between AIx and DAS28-ESR suggests that disease activity could affect arterial stiffness in RA.

Sex-Specific Association of Left Ventricular Hypertrophy With Rheumatoid Arthritis.

Objectives: Clinical expression of rheumatoid arthritis (RA) varies by gender, but whether cardiovascular disease (CVD) is gender related in RA is unknown. Left ventricular (LV) hypertrophy (LVH) is a hallmark of CVD in RA patients. We investigated whether the association of LVH with RA is gender driven.Methods: Consecutive outpatients with established RA underwent echocardiography with measurement of LVH at baseline and one follow-up. All participants had no prior history of CVD or diabetes mellitus. We assessed CVD risk factors associated with LVH at follow-up, including sex, age, arterial blood pressure, and body mass index (BMI). We also evaluated inflammatory markers, autoimmunity, disease activity, and the use of RA medications as predictors of LVH.Results: We recruited 145 RA patients (121 females, 83%) and reassessed them after a median (interquartile range) of 36 months (24–50). At baseline, women were more dyslipidemic but otherwise had fewer CVD risk factors than men, including less prevalent smoking habit and hypertension, and smaller waist circumference. At follow-up, we detected LVH in 42/145 (44%) RA patients. LV mass significantly increased only in women. In multiple Cox regression analysis, women with RA had the strongest association with LVH, independently from the presence of CVD risk factors (OR, 6.56; 95% CI, 1.34–30.96) or RA-specific characteristics (OR, 5.14; 95% CI, 1.24–21.34). BMI was also significantly and independently associated with LVH.Conclusion: Among established RA patients, women carry the highest predisposition for LVH.

Cardiovascular Risk in Rheumatoid Arthritis: Literature Review.

Rheumatoid arthritis (RA) is the most common inflammatory arthritis disease with a worldwide prevalence of 1–3%. RA patients are at higher risk of atherosclerosis than their matched age-sex controls. Cardiovascular diseases (CVDs) account for a 50% risk of increased mortality and morbidity in RA. The pattern of CVD in RA patients differs from that in the general population; RA patients are more likely to have silent ischemic heart disease, sudden death, heart failure, and die early. RA patients tend to have a 5–10 years reduction in their life span than their matched healthy population. Traditional (classical) CV risk factors work separately or synergistically with the underlying inflammation to increase CVD risk in RA. Moreover, inflammation is defined as an independent CVD risk factor. This literature review aims to discuss the traditional CVD risk factors and their association with inflammation in RA.

Long-term outcomes after coronary artery bypass surgery in patients with rheumatoid arthritis

Objective To investigate the long-term outcomes of coronary artery bypass grafting surgery (CABG) in patients with rheumatoid arthritis (RA). Methods Patients with RA (n = 378) were retrospectively compared to patients without RA (n = 7560), all treated with CABG in a multicentre, population-based cohort register study in Finland. The outcomes were studied with propensity score-matching adjustment for baseline features. The median follow-up was 9.7 years. Results Diagnosis of RA was associated with an increased risk of mortality after CABG compared to patients without RA (HR 1.50; CI 1.28–1.77; p < .0001). In addition, patients with RA were in higher risk of myocardial infarction during the follow-up period (HR 1.61; CI 1.28–2.04; p < .0001). Cumulative rate of repeated revascularization after CABG was 14.4% in RA patients and 12.0% in control patients (p = .060). Duration of RA before CABG (p = .011) and preoperative corticosteroid usage in RA (p = .041) were independently associated with higher mortality after CABG. There were no differences between the study groups in 30-d mortality or in the post-operative usage of cardiovascular medications. Conclusions RA is independently associated with worse prognosis in coronary artery disease treated with CABG. Preoperative corticosteroid use and longer RA disease duration are additional risk factors for mortality. Key messages Patients with rheumatoid arthritis (RA) have impaired long-term outcomes after coronary artery bypass surgery (CABG). Glucocorticoid use before CABG and duration of RA are associated with higher mortality. Special attention should be paid in secondary prevention of cardiovascular disease in RA patients after CABG.

Diabetes mellitus and cardiovascular risk management in patients with rheumatoid arthritis in a large international audit

Abstract Background The cardiovascular disease (CVD) risk in patients with rheumatoid arthritis (RA) is comparable to that of patients with diabetes mellitus (DM). Although several studies have indicated high prevalence's of DM in RA patients, little is known about how this affects their CVD risk. Objectives To examine indications for, and use of antihypertensive treatment (a-HT) and lipid-lowering therapy (LLT) in RA patients with DM (RA-DM) and RA patients without DM (RAwoDM). Further, to compare the prevalence of various types of CVD across RA-DM and RAwoDM. Methods The cohort was derived from the SUrvey of cardiovascular disease Risk Factor in patients with Rheumatoid Arthritis (SURF-RA), which was performed in 53 centres/17 countries in 5 world regions (West and East Europe; North and Latin America; and Asia) from 2014 - 2019. Indication for a-HT was defined as: 1) systolic/diastolic blood pressure (BP) ≥140/90 mm Hg, 2) self-reported hypertension, and/or 3) current use of a-HT. Indication for LLT was defined according to ESC guidelines. CVD risk estimates (by SCORE) were multiplied by 1.5 according to EULAR recommendations. Target treatment targets for BP and lipids were defined according to ESC guidelines applicable at the time data were recorded. Results Presence of comorbid DM was available in 10 602 (73.1%) of the 14 503 RA patients included in SURF-RA, of whom 75 and 1262 patients reported DM type 1 and type 2, respectively (total 1337 patients, 12.6%). Although less often current smokers, RA-DM patients were more often previous smokers, male sex and had higher body mass index compared to RAwoDM (p&amp;lt;0.0001 for all). a-HT (84.7% vs 62.3%) and LLT (100% vs 47.2%) were more frequently indicated in RA-DM than in RAwoDM patients (p&amp;lt;0.0001 for both). RA-DM were more likely than RAwoDM to receive a-HT on indication (60.4% vs 57.6%, p&amp;lt;0.0001), while the difference in LLT use on indication was not significantly different (45.7% vs 42.5%, p=0.06). Moreover, RA-DM compared to RAwoDM patients had more often reached treatment goals when on a-HT (60.7% vs 54.1%, p&amp;lt;0.0001) and LLT (62.8% vs 48.9%, p&amp;lt;0.0001). Finally, the risk of all recorded established CVD (coronary heart disease, stroke, peripheral artery disease and atrial fibrillation) was increased by a factor of 2 to 3 in RA-DM compared to RAwoDM (Figure). Conclusion The effect of RA and comorbid DM on CVD risk appears to be additive. While CVD preventive medications are more often indicated in RA-DM than in RAwoDM patients, they are also more likely to receive such therapy and to reach CVD preventive treatment goals. The latter finding may be due to more developed CVD preventive care in DM compared to RA patients. Improved CVD preventive systems for patients with RA are warranted. CVD in RA patients with and without DM Funding Acknowledgement Type of funding source: Other. Main funding source(s): Lilly

Prediction of cardiovascular events in rheumatoid arthritis using risk age calculations: evaluation of concordance across risk age models

BackgroundIn younger individuals, low absolute risk of cardiovascular disease (CVD) may conceal an increased risk age and relative risk of CVD. Calculation of risk age is proposed as an adjuvant to absolute CVD risk estimation in European guidelines. We aimed to compare the discriminative ability of available risk age models in prediction of CVD in rheumatoid arthritis (RA). Secondly, we also evaluated the performance of risk age models in subgroups based on RA disease characteristics.MethodsRA patients aged 30–70 years were included from an international consortium named A Trans-Atlantic Cardiovascular Consortium for Rheumatoid Arthritis (ATACC-RA). Prior CVD and diabetes mellitus were exclusion criteria. The discriminatory ability of specific risk age models was evaluated using c-statistics and their standard errors after calculating time until fatal or non-fatal CVD or last follow-up.ResultsA total of 1974 patients were included in the main analyses, and 144 events were observed during follow-up, the median follow-up being 5.0 years. The risk age models gave highly correlated results, demonstrating R2 values ranging from 0.87 to 0.97. However, risk age estimations differed > 5 years in 15–32% of patients. C-statistics ranged 0.68–0.72 with standard errors of approximately 0.03. Despite certain RA characteristics being associated with low c-indices, standard errors were high. Restricting analysis to European RA patients yielded similar results.ConclusionsThe cardiovascular risk age and vascular age models have comparable performance in predicting CVD in RA patients. The influence of RA disease characteristics on the predictive ability of these prediction models remains inconclusive.

Examination of the Epicardial Fat Area in Patients with Rheumatoid Arthritis by Computed Tomography of the Thorax

Objective: Rheumatoid arthritis (RA) is an autoimmune and inflammatory disease. The prevalence of cardiovascular diseases (CVDs) increases in RA. The CVDs were shown as the major cause of death in RA. In this study, it was aimed to determine the difference between the patients and the control group by measuring the epicardial adipose tissue (EAT) at the left major coronary artery, which is known as one of the major risk factors for CVDs in RA patients who underwent computerized tomography (CT) of the thorax due to any reason, through the CT. Method: The study includes 87 patients diagnosed with RA in the remission period and 45 healthy people as the control group. The files and archive records were reviewed and the clinical features of the patient and control groups, the EAT areas in the thorax CT performed, ascending aorta, pulmonary truncus, and pulmonary artery diameters, as well as, the cardiothoracic rates (CTR) measured with CT were recorded. Results: There was no significant difference between the groups in terms of age and gender (p>0.05). It was determined that the EAT measured with CT increased in patients diagnosed with RA compared to the control group and this increase was closely related to the aortic and pulmonary artery width (p<0.05). In addition, the increase in the EAT area was directly proportional with the CTR in patients diagnosed with RA (p<0.05). It was seen that the ascending aorta diameter, pulmonary truncus diameter, and right and left pulmonary artery diameters increased compared to the control group (p<0.05). Conclusions: In the present study, it was determined that the EAT measured with CT increased in patients with RA compared to normal people and this increase was closely related to the aortic and pulmonary artery width. In addition, the increase in the EAT area was directly proportional with the CTR in patients diagnosed with RA. The patients with RA were under a significant risk compared to normal people in terms of the development of CVDs. It is considered that more prospective studies including patients diagnosed with RA should be conducted.

Cardiorenal syndrome in patients with rheumatoid arthritis

In 2008, the term cardiorenal syndrome (CRS) was proposed by the Acute Dialysis Quality Initiative (ADQI) Group to denote pathological reciprocal conditions involving the heart and kidneys, which develop due to acute or chronic dysfunction of one of the organs, followed by acute or chronic dysfunction of the other one. The problem of CRS in patients with rheumatoid arthritis (RA) has not been studied. Of the greatest interest is CRS type 5 or secondary CRS that occurs in patients with systemic diseases, including in those with RA. Currently, there is no doubt that the risk of developing cardiovascular diseases in RA patients and the prevalence of non-ischemic and ischemic chronic heart failure (CHF) are higher than those in the general population. There is evidence that the prevalence of chronic kidney disease (CKD) and renal pathology-associated cardiovascular risk factors (RF) is high in patients with RA. In addition to traditional RFs for cardiovascular and kidney diseases, autoimmune inflammation is an independent predictor for CHF and CKD. The characteristics of CRS in RA should be investigated to develop an effective treatment strategy for this category of patients.

Functional implications of single nucleotide polymorphisms rs662 and rs854860 on the antioxidative activity of paraoxonase1 (PON1) in patients with rheumatoid arthritis

BackgroundAtherosclerosis leading to cardiovascular disease (CVD) is the main cause of mortality and morbidity in patients with rheumatoid arthritis (RA). Paraoxonase1 (PON1) is the best understood member of plasma paraoxonases with anti-atherogenic properties.Patients and methodsSpanish RA (n = 549) consecutively recruited from 1 single center and 477 ethnically matched healthy controls were included in a case-control study. The concentration of PON1 was evaluated by means of an enzyme-linked immunosorbent sssay (ELISA). An arylesterase/paraoxonase assay kit was used to evaluate PON1 activity. Sample genotyping was performed by using TaqMan assays-on-demand. All results were expressed as medians ± interquartile range. One-way ANOVA comparisons were done using a nonparametric Kruskall-Wallis test. P values under 0.05 were considered to be significant.ResultsThe concentration of PON1 in the RA group was higher than in control group (p = 0.0003), although the differences were not significant when PON1 activities were compared between both groups. No significant differences were found related to distributions of rs662 genotypes in RA patients compared to healthy controls. Among rs854860 polymorphisms, overall genotype was widely distributed between RA patients and controls. Overall PON1 concentration in plasma was not significantly different between individuals carrying any of rs662 (p = 0.8501) or rs854860 (p = 0.2741) polymorphisms. Although PON1 levels were not associated with any of the SNPs in the study, differences appear when enzyme activities are compared for each SNP separately. CVD in RA patients correlate with increased PON1 levels and lower PON1 activity.ConclusionsAlthough protective role of PON1 against oxidative damage in vivo could be related to other activities, in our study arylesterase activity was useful to identify phenotypic differences with emphasis placed on two SNPs coding for nonconservative amino acid changes in the functional protein.

Impact of anti-rheumatic treatment on cardiovascular risk in Asian patients with rheumatoid arthritis.

To estimate the incidence of cardiovascular disease (CVD) in Asian patients with rheumatoid arthritis (RA) and to evaluate the impact of anti-rheumatic treatment on the development of CVD. A retrospective cohort of Asian patients with RA was established to identify the incidence rate (IR) of CVD in RA patients. The cohort was generated using the Korean National Healthcare claims database, which contained claims from Jan 2009 to Dec 2013. A total of 137,512 RA patients were identified; individuals with a history of CVD for 6 months or more before the index date were excluded. Nested case-control samples were drawn from the full study population with a case:control ratio of 1:4 (n = 7102 cases; n = 27,018 controls without CVD). A conditional multivariate regression model was used to evaluate the impact of anti-rheumatic treatment on the development of CVD in RA patients after matching for age, sex, RA index date, comorbidities, and drug use (e.g., antiplatelet agents and cholesterol-lowering agents). The IR for development of overall CVD in RA patients was 182.1 (95% CI: 178.4-185.9) per 10,000 person-years. In models adjusted for other CVD risk factors, disease-modifying anti-rheumatic drugs (DMARDs) (OR = 0.79) were protective against CVD, and biologic DMARDs were not significantly associated with CVD risk (OR = 0.85). Corticosteroids (OR = 1.26) and NSAIDs (nonselective NSAIDs: OR = 1.32, Cox-2 inhibitors: OR = 1.31) were risk factors for CVD in RA patients. The use of DMARDs is protective against CVD, while corticosteroids and NSAIDs increased the risk of CVD in RA patients.

Comorbidity in rheumatoid arthritis: A focus on cardiovascular diseases

Cardiovascular diseases (CVD) in patients with rheumatoid arthritis (RA) are ranked first in the structure of comorbidity and mortality. This review includes recent data on common pathogenic mechanisms of inflammation and atherosclerosis, the impact of traditional and specific risk factors, biomarkers of CVD in RA patients. Variants of CVD in RA, the possible pathogenic mechanisms of their development and methods of diagnosis and prevention are described.

Abstract 15297: Active Rheumatoid Arthritis is Associated With Subclinical Left Ventricular Systolic Myocardial Dysfunction

Introduction: Patients with rheumatoid arthritis (RA) have comparable cardiovascular risk to patients with diabetes mellitus. Lately, disease activity has emerged as a new, independent risk factor for cardiovascular disease in RA patients. Hypothesis: We tested if RA disease activity was associated with subclinical systolic left ventricular (LV) dysfunction independent of traditional cardiovascular risk factors. Methods: Echocardiography was performed in 78 patients with active RA (Simplified Disease Activity Index [SDAI] &gt;3.3), 41 patients in remission (SDAI ≤3.3), and 46 controls, all without known cardiac disease. LV endocardial systolic function was determined by biplane Simpson ejection fraction and LV myocardial function by stress-corrected midwall shortening (scMWS) and global longitudinal strain (GLS). Results: Patients with active RA had higher frequencies of hypertension, diabetes and use of disease modifying antirheumatic drugs (all p&lt;0.05) compared to patients in remission, while age and sex did not differ from RA patients in remission (Table). LV ejection fraction was normal in all groups, while mean GLS and scMWS were reduced in RA patients with active disease compared to RA in remission (p&lt;0.05) (Table). In multivariate analyses, having active RA was associated with lower GLS (β=0.21) and scMWS (β=-0.22, both p&lt;0.05) independent of cardiovascular risk factors and LV ejection fraction. Assessment of RA disease activity by other composite scores yielded similar results. Conclusions: Active RA is associated with subclinical reduced LV systolic myocardial function despite normal ejection fraction, and independent of presence of hypertension and diabetes.

Therapeutic potential of folic acid supplementation for cardiovascular disease prevention through homocysteine lowering and blockade in rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that preferentially affects joints, and characterized by an approximately two-fold increased risk of cardiovascular diseases compared with the general population. Beyond classical cardiovascular risk factors, systemic inflammatory markers are primarily involved. Hence, anti-inflammatory strategies such as homocysteine-lowering interventions are warranted. Indeed, hyperhomocysteinemia is commonly found in RA patients as a result of both genetic and non-genetic factors including older age, male gender, disease-specific features and disease-modifying antirheumatic drugs. Most importantly in the pathophysiology of hyperhomocysteinemia and its related cardiovascular diseases in RA, there is a bi-directional link between immuno-inflammatory activation and hyperhomocysteinemia. As such, chronic immune activation causes B vitamins (including folic acid) depletion and subsequent hyperhomocysteinemia. In turn, hyperhomocysteinemia may perpetrate immuno-inflammatory stimulation via nuclear factor ƙappa B enhancement. This chronic immune activation is a key determinant of hyperhomocysteinemia-related cardiovascular diseases in RA patients. Folate, a homocysteine-lowering therapy could prove valuable for cardiovascular disease prevention in RA patients in the near future with respect to homocysteine reduction along with blockade of subsequent oxidative stress, lipid peroxidation, and endothelial dysfunction. Thus, large scale and long term homocysteine-lowering clinical trials would be helpful to clarify the association between hyperhomocysteinemia and cardiovascular diseases in RA patients and to definitely state conditions surrounding folic acid supplementation. This article reviews direct and indirect evidence for cardiovascular disease prevention with folic acid supplementation in RA patients.