Atherosclerosis In Rheumatoid Arthritis Research Articles

New insights to the mechanisms underlying atherosclerosis in rheumatoid arthritis.

Rheumatoid arthritis (RA) is an inflammatory circumstance, which has been associated with increased risk of cardiovascular disease (CVD). Although RA management has been promoted, mortality rate due to CVD remains remarkable. Approximately, 50% of premature death cases in RA are attributable to CVD. RA patients develop atherosclerosis in a greater amount than the general population. Moreover, atherosclerotic lesions develop rapidly in RA patients and might be more susceptible to rupture. The inflammatory condition of RA, such as cytokines, abnormally activated immune cells, play a role in the initiation, perpetuation and exacerbation of atherosclerosis. RA and CVD have genetic and environmental contributing risk factors in common, implying to potential coincidence of both disorders. Accelerated atherosclerosis in RA is attributed to inflammation, which carries its role out both through modulation of traditional risk factors and direct effect on the vessel wall. Hence, anti-inflammatory medications in RA like tumor necrosis factor blockers might have a beneficial effect on preventing cardiovascular development. Increasing age, smoking, hypertension, male gender, hypercholesterolemia and diabetes are enumerated as traditional CVD risk factors. Hopefully, further understanding of the cardiovascular risk factors by perceiving the disease conditions behind CVD, will improve management of cardiovascular risks in patients with RA.

Influence of coronary artery disease and subclinical atherosclerosis related polymorphisms on the risk of atherosclerosis in rheumatoid arthritis

A genetic component influences the development of atherosclerosis in the general population and also in rheumatoid arthritis (RA). However, genetic polymorphisms associated with atherosclerosis in the general population are not always involved in the development of cardiovascular disease (CVD) in RA. Accordingly, a study in North-American RA patients did not show the association reported in the general population of coronary artery disease with a series of relevant polymorphisms (TCF21, LPA, HHIPL1, RASD1-PEMT, MRPS6, CYP17A1-CNNM2-NT5C2, SMG6-SRR, PHACTR1, WDR12 and COL4A1-COL4A2). In the present study, we assessed the potential association of these polymorphisms with CVD in Southern European RA patients. We also assessed if polymorphisms implicated in the increased risk of subclinical atherosclerosis in non-rheumatic Caucasians (ZHX2, PINX1, SLC17A4, LRIG1 and LDLR) may influence the risk for CVD in RA. 2,609 Spanish patients were genotyped by TaqMan assays. Subclinical atherosclerosis was determined in 1,258 of them by carotid ultrasonography (assessment of carotid intima media thickness and presence/absence of carotid plaques). No statistically significant differences were found when each polymorphism was assessed according to the presence/absence of cardiovascular events and subclinical atherosclerosis, after adjustment for potential confounder factors. Our results do not show an association between these 15 polymorphisms and atherosclerosis in RA.

Abatacept and cardiovascular risk in rheumatoid arthritis: update

Cardiovascular events (CVEs), such as myocardial infarction, stroke, and sudden cardiac death, which are due to the early development and rapid progression of atherosclerosis, are one of the main causes of mortality in rheumatoid arthritis (RA). Traditional risk factors (TRFs) and immunoinflammatory mechanisms underlying the pathogenesis of these diseases are shown to be responsible for atherosclerosis and its clinical manifestations in RA. Since the key role in the development of atherosclerosis and related CVEs in RA is played by chronic inflammation and autoimmune disorders, effective anti-inflammatory therapy occupies an important place in the prevention of the latter. The review gives an update on the effect of abatacept on overall mortality and CVEs, TRFs for cardiovascular disease, and the clinical and subclinical manifestations of atherosclerosis in RA.

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.

Apelin concentrations are associated with altered atherosclerotic plaque stability mediator levels and atherosclerosis in rheumatoid arthritis

Background and aimsApelin-APJ signaling reduces cardiovascular disease (CVD) risk. In rheumatoid arthritis (RA), the atherosclerosis burden and plaque vulnerability to rupture are increased. We explored relationships between apelin concentrations and subclinical CVD in RA. MethodsApelin levels were measured in 235 (114 black, 121 white) RA patients. Associations between apelin concentrations and ultrasound determined carotid artery intima-media thickness (cIMT) and plaque, and levels of matrix metalloproteinase (MMP)-2 and -9 that mediate plaque stability and vulnerability respectively, were identified in confounder adjusted multivariate regression analysis. ResultsIn all patients, apelin concentrations were directly associated with those of MMP-2 (β (SE) = 0.324 (0.112), p = 0.004) and inversely with those of MMP-9 (β (SE) = -0.239 (0.060), p = 0.000). Apelin concentration-subclinical CVD relations were influenced by population origin, RA disease activity, erythrocyte sedimentation rate (ESR) and interleukin (IL)-6 concentrations (interaction p = 0.001 to 0.04). Accordingly, the apelin-MMP-2 concentration relationship was reproduced in white (β (SE) = 0.367 (0.146), p = 0.01) but not black RA patients (β (SE) = 0.197 (0.220), p = 0.4), and only in those without (but not with) large erythrocyte sedimentation rates (β (SE) = 0.428 (0.143), p = 0.003) or interleukin-6 levels (β (SE) = 0.485 (0.288), p = 0.04). By contrast, the apelin-MMP-9 concentration relation was reproduced more consistently. Apelin levels were inversely related to cIMT in patients with RA remission or mild (β (SE) = -0.068 (0.033), p = 0.04) but not moderate or high disease activity (β (SE) = 0.015 (0.112), p = 0.7). ConclusionsApelin concentrations are associated with altered plaque stability mediator levels and atherosclerosis in patients with RA. These relations are partially dependent on population origin and systemic inflammatory status.

LBPS 02-11 ARTERIAL STIFFNESS IS ASSOCIATED WITH INFLAMMATORY ACTIVITY IN PATIENTS WITH RHEUMATOID ARTHRITIS

Objective: Patients with rheumatoid arthritis (RA) are at higher risk of cardiovascular morbidity and mortality. Aortic stiffness (AS) is a predictor of cardio-vascular events. Chronic inflammation plays a role in the development of atherosclerosis in RA. Relationships between inflammation and AS in patients with RA are not well understood. The aim of the study was to evaluate parameters of AS and their associations with inflammatory activity in patients with RA. Design and Method: 42 patients with RA (EULAR 2010) were examined (67%female, age 59.7 ± 15.2 years, 14% smokers, 60% with AH, 47% with dyslipidemia. Median duration of RA was 9 years (interquartile range (IQR)3–17). Seropositive RA was diagnosed in 42% of patients. All patients received disease-modifying antirheumatic drugs (DMARDs), 20% - biological treatment. hs-CRP and RF were assessed in all patients. AS was measured by applanation tonometry (SphygmoCor, AtCor) and cardio-ankle vascular index (CAVI) was assessed (VaSera1500).p < 0.05 was considered significant. Results: Median CRP was 13 mg/dl (IQR 3–24 mg/dl), median RF was 32 IU/ml (IQR8–165 IU/ml). Median PWV was 9.4 m/s (IQR7–11 m/s). PWV increase > 10 m/s was observed in 16 (37.8%) patients. Patients with PWV > 10m/s were older (72.0 ± 8.5 vs 53.3 ± 14.9 years), had higher BMI (30.5 ± 5.9 vs 24.9 ± 4.5 kg/m2) and longer duration of AH (median 14 years [IQR 7.5–18] vs 0 years [IQR 0–4.5]) and higher BP levels (143 ± 21/84 ± 9 vs 124 ± 13/78 ± 9 mmHg). They also had higher levels of LDL-C (3.0 ± 1.0 vs 4.1 ± 0.8 mmol/l), plasma glucose (5.6 ± 0.9vs4.9 ± 0.8 mmol/l), hs-CRP (median 9[IQR 2–17.1] vs 22[IQR 13–56.6] mg/dl) and CAVI (9.2 ± 0.5vs7.2 ± 1.2), p < 0.05 for trend. Spearmen analysis revealed positive correlations of PWV with age (r =0.65), BMI (r = 0.53), SBP (r = 0.62), DBP (r = 0.41), LDL-C (r = 0.60), glucose (r = 0.38), AH duration (r = 0.69) and hs-CRP (0.28), р < 0.05 for trend. Multiple regression analysis confirmed that age (β = 0.3, р = 0.0012), AH duration (β = 0.4, р = 0.0001), SBP (β = 0.42, р < 0.0001) and hs-CRP-level (β = 0.26, р = 0.0004) were independent predictors of AS increase. Conclusions: Inflammatory activity is a predictor of AS increase in patients with RA receiving DMADs.

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.

Telomere Length and Coronary Atherosclerosis in Rheumatoid Arthritis.

Telomeres protect against chromosomal end damage and shorten with each cell division; their length may be a marker of cardiovascular and overall biological aging. We examined the hypothesis that reduced telomere length is associated with increased coronary atherosclerosis in rheumatoid arthritis (RA). We performed a cross-sectional study in 145 patients with RA and 87 control subjects frequency-matched for age, race, and sex. Coronary artery calcium score was determined by noncontrast cardiac computed tomography. Telomere length was measured from whole blood DNA, using real-time quantitative polymerase chain reaction and expressed as telomeric product to a single-copy gene product ratio (T/S ratio). Associations between telomere length, coronary artery calcium score, and 28-joint Disease Activity Score (DAS28) were assessed with Spearman correlation, proportional odds logistic regression, and linear regression, adjusting for age, race, and sex. Telomere length was significantly inversely correlated with age in patients with RA (ρ = -0.37, p < 0.001) and control subjects (ρ = -0.39, p = 0.001). Among patients with RA, for every interquartile range (IQR) decrease in telomere length (T/S ratio), the odds of higher coronary artery calcium score increased by 38% (95% CI: 4-60) after adjusting for age, race, and sex (p adjusted = 0.03). Telomere length was not associated with DAS28 (p adjusted = 0.17). Telomere length was not significantly different in patients with RA [median (IQR): 1.02 units (0.9-1.11)] compared to control subjects [1.05 units (0.95-1.17); p = 0.10]. Telomere length is inversely associated with coronary artery calcium score, independent of age, race, and sex in patients with RA.

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.

Associations between asymmetric dimethylarginine, homocysteine, and the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism (rs1801133) in rheumatoid arthritis

Objectives: The aim of our study was to determine whether asymmetric dimethylarginine (ADMA) levels are associated with homocysteine (Hcy) and methylenetetrahydrofolate reductase (MTHFR) C677T (rs1801133) gene variants in patients with rheumatoid arthritis (RA).Method: Serum ADMA and Hcy levels were measured in 201 RA individuals [155 (77.1%) females, median age 67 years (interquartile range 59–73)]. The MTHFR C677T polymorphism was assessed by using the LightCyclerTM System. Initially, ADMA was compared across the categories of MTHFR using a one-way analysis of variance (ANOVA), followed by a multivariate model, which accounted for Hcy, age, erythrocyte sedimentation rate (ESR), and homeostatic model assessment (HOMA).Results: In univariable analysis, ADMA differed significantly across the categories of MTHFR (p = 0.037). Patients with the MTHFR 677TT genotype had the highest ADMA levels, with a mean of 0.62 (SE = 0.03), significantly higher than either those patients carrying the MTHFR 677CT (0.55, SE = 0.01) or the MTHFR 677CC (0.55, SE = 0.01) genotype (p = 0.042) in both cases. In the multivariable model, Hcy (p = 0.022) and ESR (p < 0.001) were found to have significant positive associations with ADMA but the relationship between MTHFR gene variants and ADMA was found to be non-significant (p = 0.102).Conclusions: Hcy and ADMA are significantly associated in RA. It is plausible that abnormal Hcy metabolism plays an important role in premature atherosclerosis in RA by promoting ADMA accumulation and leading to the derangement of vascular haemostasis.

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.

Cardiovascular disease in rheumatoid arthritis: Current perspectives on assessing and mitigating risk in clinical practice.

That individuals with rheumatoid arthritis (RA) have, on average, higher rates of events related to atherosclerotic vascular disease is now well documented and accepted. However, optimal ways to identify RA patients with atherosclerosis, and treat them to mitigate cardiovascular disease (CVD) risk have not been rigorously established. As such, current guidelines for CVD screening and prevention lack an evidence base. In the context of the current understanding of the determinants of atherosclerosis in RA and the current guidelines that have been published, this review focuses on strategies for identifying RA patients at risk of CVD events, and the possible primary and secondary prevention strategies that may be effective.

The role of leptin in the pathophysiology of rheumatoid arthritis.

The past 20 years of research on leptin has provided important insights into its role in rheumatoid arthritis (RA). Leptin is one of the different adipokines produced by the adipose tissue that influences the endocrine system, energy homeostasis and the immune response in several ways. Leptin is known to have predominantly pro-inflammatory effects, especially in the setting of chronic inflammation. Animal models of arthritis have illustrated well the participation of leptin in the inflammatory response within the joints. In patients with RA, numerous studies have evaluated the concentrations of leptin in the bloodstream and/or the joint cavity, showing higher levels compared to control populations. Leptin has also been found to correlate with clinical or biological measurements of disease activity of RA. Conversely, the relationship between serum leptin and joint structural damage is less evident. Leptin may also promote the development of atherosclerosis in RA and may contribute to the cardiovascular consequences of the metabolic syndrome that coexists with RA. Indeed, leptin could be a link between inflammation, metabolic risk factors and cardiovascular diseases in RA. Finally, due to abnormal body composition phenotypes with an increased prevalence of obesity in RA, the therapeutic response to traditional DMARDs and/or biological agents may be attenuated. This review discusses the multiple interplays that have been described between leptin and the clinical, radiographic and therapeutic aspects of RA.

Atherosclerosis in rheumatoid arthritis: is it all about inflammation?

Rheumatoid arthritis (RA) has long been associated with increased cardiovascular risk, but despite substantial improvements in disease management, mortality remains high. Atherosclerosis is more prevalent in RA than in the general population, and atherosclerotic lesions progress at a faster rate and might be more prone to rupture, causing clinical events. Cells and cytokines implicated in RA pathogenesis are also involved in the development and progression of atherosclerosis, which is generally recognized as an inflammatory condition. The two diseases also share genetic and environmental risk factors, which suggests that patients who develop RA might also be predisposed to developing cardiovascular disease. In RA, inflammation and atherosclerosis are closely linked. Inflammation mediates its effects on atherosclerosis both through modulation of traditional risk factors and by directly affecting the vessel wall. Treatments such as TNF inhibitors might have a beneficial effect on cardiovascular risk. However, whether this benefit is attributable to effective control of inflammation or whether targeting specific cytokines, implicated in atherosclerosis, provides additional risk reduction is unclear. Further knowledge of the predictors of cardiovascular risk, the effects of early control of inflammation and of drug-specific effects are likely to improve the recognition and management of cardiovascular risk 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.

Insulin resistance in rheumatoid arthritis: disease-related indicators and associations with the presence and progression of subclinical atherosclerosis.

Systemic inflammation and insulin resistance (IR) are linked, yet the determinants of IR and its impact on atherosclerosis in rheumatoid arthritis (RA) are incompletely understood. The aim of this study was to explore the prevalence of IR in RA and non-RA populations and investigate whether the associations of IR with measures of atherosclerosis differ between these groups. IR was quantified using the homeostatic model assessment of IR (HOMA-IR), and was compared between RA patients and demographically matched non-RA controls. Differences in the associations between the HOMA-IR index and the Agatston coronary artery calcium (CAC) score, ultrasound-determined intima-media thickness (IMT) of the common carotid artery (CCA) and internal carotid artery (ICA), and focal plaque in the ICA/carotid bulb were compared according to RA status. Among the 195 RA patients and 198 controls studied, average HOMA-IR levels were higher in the RA group by 31%, and were consistently higher in the RA group regardless of stratification by demographic or cardiometabolic risk factors. While the HOMA-IR index was strongly and significantly associated with C-reactive protein (CRP) and interleukin-6 (IL-6) levels in the control group, the association was weaker in the RA group. Among RA patients, higher HOMA-IR levels were associated with rheumatoid factor (RF) seropositivity in men and women, and prednisone use in women only. Before adjustment, higher HOMA-IR levels were associated with all assessed measures of subclinical atherosclerosis in the control group only; associations were diminished and lost statistical significance after adjustment for cardiovascular risk factors. Among the RA patients, neither baseline nor average HOMA-IR levels were significantly associated with change in any of the atherosclerosis measures over an average of 3.2 years of followup. Although IR was higher in RA patients than in non-RA controls, higher levels may not independently impart additional risk of atherosclerosis.

Prevalence of Atherosclerosis in diabetic and non-diabetic patients with rheumatoid arthritis.

Objectives:(1) To compare the prevalence of preclinical atherosclerosis in diabetic vs. non-diabetic rheumatoid arthritis (RA) patients; (2) to determine the influence of classical and RA-related factors on atherosclerosis; (3) to assess the usefulness of combined carotid and femoral ultrasonography in detecting atherosclerosis.Methods:The study comprised 42 non-diabetic RA patients, 42 diabetic RA patients and 42 controls. Intima media thickness (IMT) was measured in the common carotid and superficial femoral arteries. These vessels were screened for atherosclerotic plaque.Results:Plaque was more prevalent in diabetic RA patients than in non-diabetic RA patients or controls. Carotid IMT and femoral IMT were higher in diabetic RA patients compared to controls. So was femoral IMT in diabetic compared to non-diabetic RA patients. The prevalence of increased IMT and plaque was comparable in carotid ultrasonography and combined carotid and femoral ultrasonography in all groups.Conclusions:Subclinical atherosclerosis was found to be higher in diabetic RA patients than in non-diabetic RA patients. The combination of carotid and femoral artery ultrasonography did not improve the detection of atherosclerosis in RA.

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.

Circulating concentrations of the novel adipokine chemerin are associated with cardiovascular disease risk in rheumatoid arthritis.

Depending on physiological context, the adipokine chemerin can reduce or enhance cardiovascular risk. We investigated whether chemerin concentrations represent cardiovascular disease risk in rheumatoid arthritis (RA). We assessed ELISA-determined chemerin concentrations and those of 4 early endothelial activation molecules as well as angiopoietin 2, which mediates angiogenesis and thereby contributes to advanced atherosclerosis, the common carotid artery intima-media thickness (cIMT), and carotid artery plaque by ultrasound in 236 patients (114 black and 122 white) with RA. Relationships were identified in potential confounder and mediator-adjusted mixed regression models. Mean (SD) chemerin and median (interquartile range) angiopoietin 2 concentrations were 114 (35) ng/ml and 2560 (2044-3341) pg/ml, respectively; the mean (SD) cIMT was 0.708 (0.110) mm, and 40.3% of patients had plaque. Chemerin concentrations were not related to those of early endothelial activation molecules, but associated with those of angiopoietin 2 [β SE = 0.002 (0.0004), p < 0.0001] and plaque [OR 1.006 (95% CI 1.00-1.013), p = 0.05] in all patients. The presence of major conventional cardiovascular risk factors, generalized and abdominal obesity, and RA severity markers modified the independent chemerin-cardiovascular risk relations (interaction p < 0.05). Consequently, chemerin concentrations were associated with cIMT in those with but not without overweight or generalized obesity and abdominal obesity [β SE = 0.001 (0.0003), p = 0.005 and 0.001 (0.0001), p = 0.001 vs -0.001 (0.0004), p = 0.2 and -0.0002 (0.0004), p = 0.6, respectively], and with plaque in those without but not with generalized obesity [OR 1.008 (95% CI) 1.000-1.016, p = 0.03 vs 1.003 (0.990-1.017), p = 0.6, respectively]. The β (SE) for the chemerin-intima-media thickness relations in patients with overweight or generalized obesity and abdominal obesity were larger than in those without these characteristics (p < 0.0001 and = 0.04, respectively). Chemerin is associated with endothelial activation and atherosclerosis in RA. Adiposity influences the chemerin-atherosclerotic phenotype relations in RA.