Subclinical Atherosclerosis In Rheumatoid Arthritis Research Articles

Relationship between Triglyceride-Glucose Index and Disease Activity and Subclinical Atherosclerosis in Rheumatoid Arthritis.

In rheumatoid arthritis (RA), insulin resistance (IR) is related to inflammatory markers, disease activity, and progression of atherosclerotic changes. Triglyceride-glucose (TyG) index is a relatively new indicator of IR. The present study aimed to investigate the relationship between TyG index, disease activity and subclinical atherosclerosis (SCA) in RA patients. The present case-control study included 100 RA patients and 50 age- and sex-matched healthy controls. All participants were subjected to careful history taking through clinical examination and standard laboratory assessment. The TyG index was calculated as TyG index = ln (Fasting triglyceride (mg/dL) × fasting glucose (mg/dL))/2. Carotid intima-media thickness (CIMT) measurement was done using B-mode ultrasound. Patients had significantly higher TyG index as compared to controls. Patients with high disease activity had significantly higher frequency of extraarticular manifestations (39.6% versus 51.6%, p = 0.028), higher Larsen score (3.8 ± 1.3 versus 2.8 ± 1.2, p < 0.001), higher anti-cyclic citrullinated peptide (anti-CCP) levels (median (IQR): 243.1 (205.0-408.0) U/ml versus 99.0 (78.0-332.5), p < 0.001), higher TyG index (4.8 ± 0.22 versus 4.67 ± 0.24, p = 0.006), and higher CIMT (0.87 ± 0.22 versus 0.77 ± 0.17 mm, p = 0.018). Patients with SCA had higher BMI (34.6 ± 6.2 versus 30.5 ± 5.3 Kg/m2, p < 0.001), higher Larsen score (3.7 ± 1.4 versus 3.1 ± 1.3, p = 0.028) and higher TyG index (4.89 ± 0.23 versus 4.64 ± 0.19, p < 0.001). Binary logistic regression analysis identified patients' age (OR (95% CI): 0.94 (0.89-0.99), p = 0.018), Larsen score (OR (95% CI): 1.93 (1.32-2.82), p = <0.001), anti-CCP (OR (95%): 1.04 (1.02-1.07), p = 0.032), and TyG index (OR (95% CI): 22.67 (2.14-240.4), p = 0.01) as significant predictors of high disease activity in multivariate analysis. IR estimated by the TyG index is related to disease activity and SCA in RA patients.

Angiopoietin-2, vascular endothelial growth factor family, and heparin binding endothelial growth factor are associated with subclinical atherosclerosis in rheumatoid arthritis

IntroductionPatients with RA are at a higher risk of developing CV diseases than the general population. The precise mechanisms are still unknown. We evaluated the associations between 8 plasma growth factors (GFs) (angiopoietin-2, EGF, HB-EGF, PLGF, TGF-α, VEGFa, VEGFc, and VEGFd) and subclinical arteriosclerosis in RA patients. Materials and methodsA total of 199 patients with RA treated at the Hospital Universitari Sant Joan de Reus (Spain) between 2011 and 2015 were included in this cross-sectional study. Carotid intima media thickness (cIMT), carotid plaque presence (cPP) and pulse wave velocity (PWV) were measured. GFs were measured with Bio-Plex Pro Human Cancer Biomarker Panel 2 (Bio-Rad). Multivariate models and partial least square discriminant analysis (PLS-DA) were used for analysis (RStudio, version 4.0.1). ResultsMultivariate models showed that angiopoietin-2 was associated with cPP and PWV in the overall cohort (OR = 1.53 and β = 0.20, respectively). VEGFc (β = 0.29), VEGFa (β = 0.26) and HB-EGF (β = 0.22) were also associated with PWV. VEGFa (OR = 2.36), VEGFd (OR = 2.29), EGF (OR = 2.62), PLGF (OR = 2.54), and HB-EGF (OR = 2.24) were associated with cPP in men. According to PLS-DA, GFs were able to distinguish between patients with and without cPP in the overall cohort, male cohort, and female cohort. In women, angiopoietin-2 was associated with PWV (β = 0.18). ConclusionsThe selected GFs were closely related to atherosclerosis in patients with RA and are potential predictors of CV disease in patients with RA.

Carotid atherosclerosis in the first five years since rheumatoid arthritis diagnosis: a cross sectional study

BackgroundSystemic inflammation, documented before rheumatoid arthritis (RA) diagnosis, is associated with accelerated atherosclerosis. We aimed to compare the prevalence of carotid plaque (CP) in RA patients in the first five years since diagnosis and healthy controls, and to determine disease characteristics associated with the presence of subclinical atherosclerosis in RA patients.MethodsThis was a cross-sectional study. We recruited 60 RA patients in the first five years since diagnosis and 60 matched healthy controls. Carotid ultrasound was performed to detect the presence of CP and measure carotid-intima media thickness (cIMT). Subclinical atherosclerosis was considered as the presence of CP and/or increased cIMT. Distribution was evaluated with the Kolmogorov-Smirnov test. Comparisons were made with Chi-square or Fisher’s exact test for qualitative variables and Student’s t or Mann-Whitney’s U test for quantitative variables. A p-value < 0.05 was considered significant.ResultsThere were no differences in the demographic characteristics between RA patients and controls. The mean disease duration was 2.66 ± 1.39 years. A higher prevalence of CP (30.0% vs. 11.7%, p = 0.013), bilateral CP (18.3% vs. 3.3%, p = 0.008), increased cIMT (30.0% vs. 6.7%, p = 0.001), and subclinical atherosclerosis (53.3% vs. 18.3%, p = < 0.001) was found in RA patients. RA patients with subclinical atherosclerosis were older (56.70 years vs. 50.00 years, p = 0.002), presented a higher prevalence of dyslipidemia (53.1% vs. 14.3%, p = 0.002), and higher prevalence of classification in moderate-high disease activity category measured by DAS28-CRP (68.8% vs. 35.7%, p = 0.010). The latter variable persisted independently associated with subclinical atherosclerosis in the binary logistic regression (OR 6.11, 95% CI 1.51–24.70, p = 0.011).ConclusionsIn the first five years since diagnosis, higher prevalence of subclinical atherosclerosis, including CP was found in RA patients. Carotid ultrasound should be considered part of the systematic CVR evaluation of RA at the time of diagnosis.

Association between periodontitis and cardiovascular health in rheumatoid arthritis patients: Prospective effect of periodontal treatment on cardiovascular risk

Rheumatoid arthritis (RA) patients are more likely to develop cardiovascular disease (CVD), which increases the risk of morbidity and mortality. Periodontitis is known to be associated with CVD, yet its relationship with CVD in RA is limited. To examine the relationship between periodontitis with subclinical atherosclerosis and with long term CVD risk. Examining if periodontitis treatment can be associated with CVD improvement was well thought out. This prospective interventional study included 49 adults with RA. Demographic, clinical and therapeutic data and laboratory markers were assessed. Dental examination for periodontitis was performed. The carotid intima media thickness (CIMT) and Framingham risk score (FRS) were evaluated. Medical treatment was provided to RA patients with periodontitis, and assessments were repeated after 6 months. The mean age of the patients was 46.4 ± 12.4 years, disease duration 10.9 ± 5.4 years and 79.6% were females. 25 (51%) patients had subclinical atherosclerosis, 30 (61.2%) had periodontitis and 25 (51%) had both. RA patients with subclinical atherosclerosis had higher clinical attachment loss (CAL) (3.12 ± 1.45) and higher probing depth (PD) (4.96 ± 1.37) compared to those without (p < 0.001). CAL (β = 0.01, 95 %CI: 0–0.01, p < 0.001), and PD (β = 0.01, 95% CI: 0–0.01; p < 0.001) were independently associated with CIMT. The 30 patients after treatment of periodontitis showed an average improvement in the mean CIMT (0.14 mm, p < 0.001). Periodontitis is associated with subclinical atherosclerosis in RA. Treatment of periodontitis could improve the cardiovascular health in RA patients and prompts physicians to early diagnose and treat periodontitis.

The comparison of cardiovascular disease risk prediction scores and evaluation of subclinical atherosclerosis in rheumatoid arthritis: a cross-sectional study.

Primary objectives estimated prevalence of traditional cardiovascular disease (CVD) risk factors and compared different CVD risk prediction algorithms in an Indian rheumatoid arthritis (RA) population. Secondary objectives evaluated associations between carotid intima-media thickness (CIMT) and subclinical atherosclerosis (SCA) with CVD risk factors and CVD risk scores. The presence of CVD risk factors were recorded, and 10-year CVD risk was predicted using Framingham risk scoring (FRS) using lipids (FRS-Lipids), FRS using body mass index (FRS-BMI), QRISK-2, SCORE, and the algorithm recommended by ACC/AHA (ASCVD). CIMT was measured on the far-wall of the common carotid artery. Subclinical atherosclerosis was defined as CIMT > 0.9mm or the presence of carotid plaque. A total of 332 patents were enrolled, 12% had diabetes mellitus, 21.4% hypertension, and 6.9% were current/past smokers. Proportions of RA with predicted 10-year CVD risk > 10% varied from 16.2 to 41.9% between scores. Highest magnitude of risk was predicted by FRS-BMI. Agreement between scores in predicting risk was moderate in general. Mean CIMT was 0.70 ± 0.15mm. Age, male sex, and extra-articular manifestations associated with greater CIMT. All risk scores except SCORE moderately correlated with CIMT. About one-seventh had SCA defined as CIMT > 0.9mm or the presence of carotid plaques, associated with increasing age, male gender, or higher ratio of total cholesterol to high-density lipoprotein cholesterol. ASCVD and QRISK-2 scores had maximum area under curve for distinguishing SCA. Individual CVD risk scores predict 10-year CVD risk differently in Indian patients with RA, and require validation for predicting hard end points (CVD events, mortality). Key Points • Diabetes mellitus and hypertension are the most prevalent cardiovascular disease risk factors in Indian patients with RA. • Individual cardiovascular risk prediction scores predict risk differently in Indian patients with RA, highest risk being predicted by the FRS-BMI. • Carotid intima-media thickness in RA associated with increasing age, male sex and extra-articular manifestations. • 14% RA had subclinical atherosclerosis, associated with increasing age, male sex, and higher total cholesterol to HDL-C ratio, best distinguished by ASCVD and QRISK-2 scores.

Plasma pentraxin 3 is associated with progression of radiographic joint damage, but not carotid atherosclerosis, in female rheumatoid arthritis patients: 3-year prospective study

Background: Pentraxin 3 (PTX3) has an important role in inflammation, immunity, and atherosclerosis. Rheumatoid arthritis (RA) is a chronic inflammatory disease featuring both joint damage and atherosclerosis. We investigated whether the plasma PTX3 level was associated with progression of joint destruction and subclinical atherosclerosis in RA patients.Methods: Plasma PTX3 levels were measured in 72 women with RA and 80 female control subjects. In RA patients, we also evaluated clinical characteristics, medications, and at one and three years, joint damage and atherosclerosis. Then we investigated whether PTX3 was associated with progression of joint destruction or an increase of carotid intima-media thickness (IMT).Results: Plasma PTX3 levels were significantly higher in the RA patients than in healthy controls (4.05 ± 2.91 ng/mL vs. 1.61 ± 1.05 ng/mL, p < .001). By multivariate linear regression analysis, the plasma pentraxin 3 level was independently associated with radiographic progression of joint damage for 3 years in the RA patients after adjustment for age, disease duration, body mass index, rheumatoid factor, MMP-3, Disease Activity Score 28-ESR, postmenopausal status, current use of corticosteroids and biologic use. On the other hands, pentraxin 3 was not associated with an increase of carotid intima-media thickness in RA patients.Conclusion: Female RA patients had elevated plasma PTX3 levels compared with control female subjects. PTX3 was independently associated with radiographic progression of joint damage in the RA patients, but not with carotid atherosclerosis.

Prevalence and associated factors of subclinical atherosclerosis in rheumatoid arthritis at the university hospital of Kinshasa

BackgroundRheumatoid arthritis (RA) is associated with a 5 to 10 years reduction in life expectancy due to premature atherosclerosis. This reduction is the consequence of traditional cardiovascular risk factors (TCRF) as well as systemic inflammation. The aim of the present study was to describe the prevalence and factors associated with subclinical atherosclerosis in RA at the University Hospital of Kinshasa (UHK).MethodsPatients with a diagnosis of RA based on the 2010 ACR/EULAR criteria were included in this cross-sectional study from 1 June 2014 to 31 May 2015 at the UHK. RA disease activity was measured using the DAS28-ESR. Active RA was defined by a DAS 28 > 2.6. Severe RA was defined by the presence of extra-articular manifestation, joint erosions on X-rays or HAQ ≥0.5. An assessment of subclinical atherosclerosis was performed by the measurement of the carotid intima-media thickness (cIMT) using two-dimensional ultrasonography. Subclinical atherosclerosis was defined by a cIMT ≥0.9 mm. A diagnosis of atheroma plaque was retained when the cIMT was ≥1.5 mm. The association between subclinical atherosclerosis and potential risk factors was modeled using logistic regression analysis.ResultsWe recruited 75 patients. The average age was 51.8 ± 14.6 years, with a sex ratio F/M of 4. The prevalence of subclinical atherosclerosis was 32%. In logistic regression being a woman of ≥55 years old (aOR 10.6, 95% CI [2.087–53.82], p = 0.028), DAS28-ESR > 2.6 (aOR 3.5,95% CI [1.55–10.38], p = 0.044), severe RA (aOR 32.6,95% CI [1.761–60.37],p = 0.035), high blood pressure (aOR 22.4,95% CI [5.04–99.41], p = 0.005) and obesity (aOR 32.3, 95% CI [2.606–40.73], p = 0.026) emerged as factors associated with subclinical atherosclerosis.ConclusionSubclinical atherosclerosis is common in RA patients attending the UHK. It appears to be associated with RA disease activity and severity apart from traditional cardiovascular risk factors. These results suggest that early management of subclinical atherosclerosis targeting remaining RA disease activity and cardiovascular risk factors could slow down progression to clinical cardiovascular disease.

Common atherosclerosis genetic risk factors and subclinical atherosclerosis in rheumatoid arthritis: the relevance of disease duration

Rheumatoid arthritis (RA) is a common systemic autoimmune disease characterized by increased cardiovascular morbidity. Several previous studies assessed associations between common atherosclerotic genetic risk factors and subclinical atherosclerosis (SA) in RA patients, yet most of them gave negative results. We undertook a cross-sectional study to evaluate the association between previously reported SNPs and subclinical atherosclerosis in a cohort of Polish RA patients. 29 SNPs associated with atherosclerosis in general population were genotyped in 289 RA patients: 116 patients with SA (increased carotid intima–media thickness and/or presence of carotid plaque) and 173 patients without SA. To assess the cumulative effect of SNPs we calculated 3 weighted genetic risk scores: GRSIMT, GRSCP and GRSCAD, comprising intima–media thickness-associated SNPs, carotid plaque-associated SNPs and coronary artery disease-associated SNPs, respectively. None of the SNPs showed a significant association with SA. However, we found an association between SA and GRSIMT. Interestingly, this association was limited to patients with short disease duration (P = 0.00004 vs. P > 0.5, for comparison of GRSIMT among patients within the 1st quartile of disease duration vs. others, respectively). Patients within the 1st quartile of disease duration were more frequently disease modifying anti-rheumatic drugs (DMARDs)-naïve and less frequently treated with biologics. Our study suggests that in patients with early RA subclinical atherosclerosis may be driven by similar genetic factors as in general population, while in long-lasting disease, the role common genetic risk factors may decrease. Possibly, this effect may be due to the influence of DMARDs.

Variables associated with subclinical atherosclerosis in a cohort of rheumatoid arthritis patients: Sex-specific associations and differential effects of disease activity and age.

ObjectiveTo advance the study of variables associated with subclinical atherosclerosis in rheumatoid arthritis (RA) with special consideration for the degree of disease activity, age and gender.MethodsThe carotid intima-media thickness (cIMT) and the presence of carotid atherosclerotic plaques along with clinical and biochemical characteristics were determined in 214 RA patients.ResultsAdjusted analysis reveals that men had a 0.059 mm significantly increased cIMT compared with women (p = 0.001; R2 = 3.8%) and that age was associated with cIMT (β = 0.0048 mm; p = 0.0001; R2 = 16%). Interestingly, we observed a significant interaction between gender and age. Thus, the effect of age on cIMT was significantly increased (12%) in men compared with women (p-value for interaction term = 0.041). Moreover, adjusted multivariable linear regression analysis revealed that disease activity score (DAS28) was significantly associated with cIMT in women (β = 0.021; p = 0.018: R2 = 0.03) but not men. In particular, women with high disease activity had a 0.079 mm increased cIMT compared with women in remission (p = 0.026). In addition, men in remission had a 0.134 mm increased cIMT compared with women in remission (p = 0.003; R2 = 8.7%). Active patients did not exhibit differences in cIMT values. Furthermore, 43% of patients presented carotid plaques. The variables independently associated with carotid plaques were age, smoking, health assessment questionnaire, erythrocyte sedimentation rate and rheumatoid factor (p<0.0001; R2 = 46%).ConclusionIn our cohort of patients with RA, DAS28 and age are differentially associated with cIMT in men and women. Our findings could explain the contradictory results that have previously been published in the literature.

Brachial artery flow-mediated dilation and carotid intima-media thickness for assessment of subclinical atherosclerosis in rheumatoid arthritis

ObjectiveThe aim of this study was to assess subclinical atherosclerosis in rheumatoid arthritis (RA) patients using flow-mediated dilation (FMD) and carotid intima–media thickness (CIMT) and find their relation to disease activity.Patients and methodsTotally, 30 RA patients without cardiac involvement and 10 controls were included in the study. Disease activity was evaluated using disease activity score 28 (DAS28) score. Low disease activity is defined by DAS28 of 3.2 or less, moderate disease activity as DAS28 3.3–5.3, and severe disease activity as DAS28 of 5.4 or more. Endothelial dysfunction is considered to be present when FMD on B-mode ultrasonography is below 4.5%. CIMT was calculated by measuring the greatest distance between lumen–intima and media–adventitia interface [mean value of two sides (right and left) was taken] using B-mode ultrasonography.ResultsThe mean CIMT was significantly higher in the RA patients (1.8±0.2) than in healthy controls (1.5±0.1) (P=0.001). Taking the mean±SD of the control group (1.6 mm) as the upper limit of the normal CIMT, 22 (73.3%) RA patients and three (30%) controls had abnormal mean CIMT, which was statistically significant. Brachial FMD% in RA patients was significantly lower (22.9±11.0) as compared with controls (35.5±23.2) (P=0.027). A statistically significant positive correlation was observed between CIMT values of patients with age, C-reactive protein, and low-density lipoprotein. There was a significant negative correlation between CIMT and hemoglobin and brachial FMD. FMD% showed a statistically significant negative correlation with age, disease duration, low-density lipoprotein, Framingham cardiovascular risk score, and mean CIMT.ConclusionCarotid ultrasound and endothelial function assessment by means of FMD may be a useful tool to predict the increased risk for cardiovascular disease in patients with RA, which requires aggressive therapy.

Association of Helicobacter Pylori Infection with Oxidative DNA Damage and Atherosclerosis in Rheumatoid Arthritis Patients

Objectives: to evaluate the associations between Helicobacter pylori (HP) with oxidative DNA damage and subclinical atherosclerosis in rheumatoid arthritis (RA) patients. Methods: Eighty RA patients were divided into two groups according to the presence of anti-HP antibodies. In addition, to forty healthy volunteers. All patients were subjected to DAS-28, ESR , hsCRP ,RF, Anti-CCP, Lipid profiles, serum anti-HP antibodies, 8-hydroxydeoxyguanosine, Oxidized LDL, IL-6,carotid intima media thickness (cIMT) and flow mediated dilatation of the brachial artery (FMD). Results: HP positive RA patients revealed significantly higher disease activity, RF, Anti-CCP, dyslipidemia, 8- OHdG, ox-LDL, cIMT and lower FMD% compared to HP negative patients. There was positive correlation between anti-HP antibodies with disease activity parameters, ox-LDL, 8-OHdG and cIMT as well as negative correlation with FMD℠. In multiple regression analysis, IgG antibodies against H pylori were associated with DAS-28 (p=p<0.001), hsCRP (p=p<0.01), 8-OHdG (p<0.01), cIMT (p<0.001) and FMD℠(p<0.001). Conclusions: Chronic infection with HP in RA patients is significantly associated with oxidative stress and DNA damage. Detection and eradication of HP infection in RA patients may reduce the burden of atherosclerosis and its associated morbidity and mortality.

Sensorineural Hearing Impairment and Subclinical Atherosclerosis in Rheumatoid Arthritis Patients Without Traditional Cardiovascular Risk Factors.

This study aims to evaluate the association of hearing impairment with carotid intima-media thickness and subclinical atherosclerosis in rheumatoid arthritis (RA) patients. A total of 41 RA patients (2 males, 39 females; mean age 46.5±10.2 years; range 20 to 63 years) with no known traditional cardiovascular risk factors were included. Routine clinical and laboratory assessments for RA patients were performed. Pure tone air (250-8000 Hz) and bone conduction (250-6000 Hz) thresholds were obtained, tympanograms and impedance audiometry were conducted. Sensorineural hearing impairment was defined if the average thresholds were ≥25 decibels. Carotid intima-media thickness was assessed and classified with a cut-off point of 0.6 mm. Thirteen patients (31.7%) had normal audition, while 28 (68.3%) had hearing impairment. Of these, 22 had bilateral sensorineural hearing impairment. Four patients had conductive hearing impairment (right in three patients and left in one patient). Patients with sensorineural hearing impairment had increased carotid intima-media thickness in the media segment of carotid common artery compared to patients with normal hearing (right ear p=0.007; left ear p=0.075). Thickening of the carotid intima-media thickness was associated with sensorineural hearing impairment in RA patients. Rheumatoid arthritis patients should be evaluated by carotid intima-media thickness as a possible contributing factor of hearing impairment in patients without cardiovascular risk factors.

Low levels of inflammation and the absence of subclinical atherosclerosis in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease. Patients with RA have an increased risk for the development of cardiovascular diseases, however, the pathophysiological mechanisms of arterial complications in RA remain to be fully elucidated. Understanding the early markers of vascular damage may aid in preventing cardiovascular complications in patients with RA. The current study investigated this by recruiting 30 patients with RA and 30 healthy subjects. Intima‑media thickness (IMT) was used to detect the presence of atherosclerotic disease and was measured in the carotid and femoral arteries. Tumor necrosis factor α, interleukin‑6 (IL‑6), IL‑8, IL‑10 and matrix metalloproteinase‑2 were measured as markers of inflammation. An IMT ≥0.9 mm was observed in 7/30 patients with RA, however, no significant differences between patients with RA and the controls were observed in the inflammatory markers analyzed. Of note, these results indicated that the appropriate management of RA may have affected the inflammatory status of these patients and consequently may have impacted upon subclinical atherosclerosis.

Carotid intima media thickness as a marker of subclinical atherosclerosis in rheumatoid arthritis: a case control study

Background: Increased cardiovascular morbidity and mortality has been observed in rheumatoid arthritis (RA) because of accelerated atherosclerosis. We measured carotid intima-media thickness (CIMT) as a surrogate marker of subclinical atherosclerosis in RA in this study. Methods: In this study 40 cases of RA and 26 matched individuals were recruited. CIMT measurements were done using B-mode ultrasound. Disease activity was assessed using DAS28, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels. Results: Mean age of the study groups was 52.45±7.43 years (range 41-69 years). Average disease duration was 9.34±4.18 years (range 5-20 years). Thirty two (32/40, 80%) cases of RA were RF positive. ESR was significantly higher in RA cases (51.75±24.13 mm Ist hr) compared to healthy controls (17.31±9.08 mm Ist hour, p <0.001). Significantly increased CIMT was observed in cases as compared to the control group (0.68 ± 0.06 mm versus 0.63±0.07; 𝑃 0.002). CIMT in the cases positively correlated with age (𝑟 = 0.500; 0.001), duration of disease (𝑟= 0.594; 𝑃 0.001). CIMT negatively correlated with HDL (𝑟 = -0.345; 0.029). Conclusions: Subclinical atherosclerosis (increase CIMT) is common in RA and correlated well with disease duration. So every patient of RA should be evaluated for development for atherosclerosis.

Brief report: lack of replication of an association between anti-citrullinated fibrinogen and subclinical atherosclerosis in patients with rheumatoid arthritis.

Results of a recent study suggested that the excess cardiovascular (CV) risk observed in patients with rheumatoid arthritis (RA) could be partially explained by the presence of immune complexes of antibodies against citrullinated proteins that locally promote and perpetuate inflammation and progression of atherosclerotic plaques. The present study was undertaken to attempt to replicate one of the observations supporting this hypothesis, i.e., association between anti-citrullinated fibrinogen (anti-Cit-fibrinogen) positivity and subclinical atherosclerosis. Three surrogate markers of atherosclerosis were assessed in 124 RA patients with no previous history of CV events: carotid intima-media thickness (CIMT) assessed by carotid ultrasonography, carotid plaques assessed by carotid ultrasonography, and Coronary Artery Calcification Score (CACS) determined by multidetector computed tomography (CT) scanning. We analyzed the relationship of these 3 subclinical atherosclerosis markers to the presence and levels of autoantibodies, including anti-Cit-fibrinogen, anti-cyclic citrullinated peptide 2 (anti-CCP-2), and rheumatoid factor (RF). Carotid plaques and CIMT >0.90 mm were present in 69.4% and 15.3%, of the patients, respectively, and the CACS was moderate or high in 21.0%. None of these surrogate markers of atherosclerosis showed a significant association with positivity for or the level of anti-Cit-fibrinogen antibodies (either against the whole protein [present in 33.9% of the patients] or against an immunodominant peptide [present in 23.4%]), anti-CCP-2 (present in 60.7%), or RF (present in 58.1%) in this series of patients with RA. Our results do not support the notion that there is a relationship between anti-Cit-fibrinogen antibodies and subclinical atherosclerosis in RA, thus calling into question the claim that these antibodies have a role in the increased risk of CV disease observed in patients with RA.

The clinical value of anti-cyclic citrullinated peptide (anti-ccp) antibodies and insulin resistance (IR) in detection of early and subclinical atherosclerosis in rheumatoid arthritis (RA)

Abstract Background Patients with rheumatoid arthritis (RA) have increased coronary atherosclerosis possibly related to several factors including insulin resistance. Anti-CCP antibodies are highly specific for RA but their association with cardiovascular morbidity has not been examined by enough studies. Aim The aim of this study was to evaluate the role of anti ccp antibodies and IR for detection of early and sub-clinical atherosclerosis in RA patients. Subjects and methods 56 RA patients and 19 age and sex matched healthy subjects were included in the present study. All patients and controls were subjected to full history, clinical examination, and laboratory investigations (including CBC, ESR, high sensitive CRP, rheumatoid factor and lipid profile). All patients were also subjected to measurement of intima-media thickness (IMT) of both carotid arteries as well as the flow mediated dilatation (FMD) of brachial artery. Also, measurements of IR (by HOMA 2) and anti-CCP were done for all subjects. Results IMT was significantly increased (P = 0.01) and FMD significantly decreased (P = 0.001) in RA patients than controls in spite of the absence of significant differences in traditional atherosclerotic risk factors. Both IR and anti-CCP (which are significantly increased in RA compared to controls, P = 0.02 and 0.001 respectively) were significantly positively correlated to IMT (P = 0.009 and 0.001 respectively) and negatively correlated to FMD (P = 0.0005 and 0.005 respectively). Conclusion IR and anti-CCP may be helpful in the early detection of subclinical atherosclerosis in RA patients.

Is Lipoprotein-Associated Phospholipase A2 a Link between Inflammation and Subclinical Atherosclerosis in Rheumatoid Arthritis?

Objective. Lipoprotein-associated phospholipase A2 (Lp-PLA2), a marker of vascular inflammation, is associated with cardiovascular disease. This prospective study of an inception cohort aimed to investigate whether the level of Lp-PLA2 is associated with subclinical atherosclerosis in patients with rheumatoid arthritis (RA). Methods. Patients from northern Sweden diagnosed with early RA were consecutively recruited into an ongoing prospective study. From these, all patients ≤60 years (n = 71) were included for measurements of subclinical atherosclerosis at inclusion (T0) and five years later (T5). Forty age- and sex-matched controls were included. The patients were clinically assessed, SCORE, Reynolds Risk Score, and Larsen score were calculated, and blood samples were drawn from all individuals at T0 and T5. Results. There was no significant difference in the level of Lp-PLA2 between patients with RA and controls (p > 0.05). In simple linear regression models among patients with RA, Lp-PLA2 at T0 was significantly associated with intima media thickness (IMT) at T0 and T5, flow mediated dilation (FMD) at T0 and T5, ever smoking, male sex, HDL-cholesterol (inversely), non-HDL-cholesterol, SCORE, Reynolds Risk Score, and Larsen score (p < 0.05). Conclusion. In this cohort of patients with early RA, the concentration of Lp-PLA2 was associated with both subclinical atherosclerosis and disease severity.

SAT0135 Low Levels of CD36 in Peripheral Blood Monocytes in Subclinical Atherosclerosis in Rheumatoid Arthritis: A Cross-Sectional Study of A Mexican Population

BackgroundRheumatoid arthritis (RA) patients have a higher risk for atherosclerosis mainly as a consequence of chronic systemic inflammation, notwithstanding, the implicated pathways have not been completely understood. CD36 is a...

AB0352 Osteoprotegerin, Disease Severity and Established Cardiovascular Disease in Rheumatoid Arthritis: A CASE Control Study

BackgroundOsteoprotegerin (OPG) may participate in the pathophysiology of rheumatoid arthritis (RA) (1). Recently reported evidence further supports a potential involvement of OPG in endothelial activation and subclinical atherosclerosis in RA...

Low levels of CD36 in peripheral blood monocytes in subclinical atherosclerosis in rheumatoid arthritis: a cross-sectional study in a Mexican population.

Patients with rheumatoid arthritis (RA) have a higher risk for atherosclerosis. There is no clinical information about scavenger receptor CD36 and the development of subclinical atherosclerosis in patients with RA. The aim of this study was to evaluate the association between membrane expression of CD36 in peripheral blood mononuclear cells (PBMC) and carotid intima-media thickness (cIMT) in patients with RA. Methods. We included 67 patients with RA from the Rheumatology Department of Hospital Civil “Dr. Juan I. Menchaca,” Guadalajara, Jalisco, Mexico. We evaluated the cIMT, considering subclinical atherosclerosis when >0.6 mm. Since our main objective was to associate the membrane expression of CD36 with subclinical atherosclerosis, other molecules related with cardiovascular risk such as ox-LDL, IL-6, and TNFα were tested. Results. We found low CD36 membrane expression in PBMC from RA patients with subclinical atherosclerosis (P < 0.001). CD36 mean fluorescence intensity had negative correlations with cIMT (r = −0.578, P < 0.001), ox-LDL (r = −0.427, P = 0.05), TNFα (r = −0.729, P < 0.001), and IL-6 (r = −0.822, P < 0.001). Conclusion. RA patients with subclinical atherosclerosis showed low membrane expression of CD36 in PBMC and increased serum proinflammatory cytokines. Further studies are needed to clarify the regulation of CD36 in RA.