Patient perspective on exercise intervention in rheumatoid arthritis with high risk of cardiovascular disease: a pilot qualitative study.

The objective of the study was to gain an insight into the perceptions and experiences of patients with rheumatoid arthritis and a high cardiovascular disease risk (CVD-RA) when undergoing an exercise intervention aimed at improving their cardiorespiratory fitness. This qualitative study was part of a pilot study, which investigated the effects of an exercise intervention on cardiorespiratory fitness in patients with CVD-RA. Six patients were invited to participate in face-to-face semi-structured interviews. We invited patients who completed the exercise intervention as well as patients who withdrew from the exercise intervention. The interviews were analyzed according to the method of thematic analysis. Six patients were interviewed, of whom four patients completed and two patients discontinued the exercise intervention. The mean (SD) age was 58 (9.7) years, the median disease duration was 10 years, and five patients were female. The analyses revealed seven themes that provided insight into perceptions and experiences: (1) ability to understand reasons for actions; (2) the need to be seen; (3) reaching their maximum effort; (4) experiencing their limits; (5) wanting personalized exercise therapy; (6) happy to be physically active; (7) benefits of exercise. Patients perceived that they were able to perform a cardiopulmonary exercise test with maximum effort and achieved the prescribed intensity of the exercise intervention. They also experienced an improvement in their physical activity by incorporating physical activity in their daily live. Overarching principles that re-occurred in the themes were: the need to be viewed as a person and the importance of feeling safe.

Do Disease-Modifying Anti-rheumatic Drugs and Exercise Therapy Have a Combined Effect on Disease Activity in Patients with RA? A Scoping Review.

PURPOSE OF REVIEW: In addition to disease-modifying anti-rheumatic drug (DMARD) treatment, exercise is increasingly promoted in patients with rheumatoid arthritis (RA). Although both are known to reduce disease activity, few studies have investigated the combined effects of these interventions on disease activity. The aim of this scoping review was to provide an overview of the reported evidence on whether a combined effect-i.e., a greater reduction in disease activity outcome measures-can be detected in studies where an exercise intervention was performed in addition to the DMARD treatment in patients with RA. This scoping review followed the PRISMA guidelines. A literature search was performed for exercise intervention studies in patients with RA treated with DMARDs. Studies without a non-exercise control group were excluded. Included studies reported on (components of) DAS28 and DMARD use and were assessed for methodological quality using version 1 of the Cochrane risk-of-bias tool for randomized trials. For each study, comparisons between groups (i.e., exercise + medication vs. medication only) were reported on disease activity outcome measures. Study data related to the exercise intervention, medication use, and other relevant factors were extracted to assess what may have influenced disease activity outcomes in the included studies. RECENT FINDINGS: A total of 11 studies were included of which 10 between-group studies on DAS28 components were made. The remaining one study focused on within-group comparisons only. Median duration of the exercise intervention studies was 5 months, and the median number of participants was 55. Six out of the 10 between-group studies reported no significant differences between groups in DAS28 components between exercise + medication vs. medication only. Four studies showed significant reductions in disease activity outcomes for the exercise + medication group compared with the medication-only group. Most studies were not adequately designed methodologically in order to investigate for comparisons of DAS28 components and had a high risk of multi-domain bias. Whether the simultaneous application of exercise therapy and DMARD medication in patients with RA has a combined effect on disease outcome remains unknown, due to weak methodological quality of existing studies. Future studies should focus on the combined effects by having disease activity as the primary outcome.

Barriers and facilitators for physical activity in rheumatic and musculoskeletal disease: a European-based survey.

Physical activity (PA) is a key strategy for improving symptoms in people with rheumatic and musculoskeletal diseases (RMDs). The aim of this study was to investigate and rank the importance of known barriers and facilitators for engaging in PA, from the perspective of people living with RMD. Five hundred thirty-three people with RMD responded to a survey (nine questions) disseminated by the People with Arthritis and Rheumatism (PARE) network of the European Alliance of Associations for Rheumatology (EULAR). The survey required participants to rank - based on their perceived importance - known PA barriers and facilitators from the literature, and specifically RMD symptoms as well as healthcare and community factors that may affect PA participation. Of the participants, 58% reported rheumatoid arthritis as their primary diagnosis, 89% were female, and 59% were between 51 and 70 years of age. Overall, participants reported fatigue (61.4%), pain (53.6%) and painful/swollen joints (50.6%) as the highest ranked barriers for engaging in PA. Conversely, less fatigue (66.8%) and pain (63.6%), and being able to do daily activities more easy (56.3%) were identified as the most important facilitators to PA. Three literature identified PA barriers, i.e., general health (78.8%), fitness (75.3%) and mental health (68.1%), were also ranked as being the most important for PA engagement. Symptoms of RMDs, such as pain and fatigue, seem to be considered the predominant barriers to PA by people with RMD; the same barriers are also the ones that they want to improve through increasing PA, suggesting a bi-directional relationship between these factors. Key Points • Symptoms of rheumatic and musculoskeletal disease (RMD) are the predominant barriers for lack of physical activity engagement. • RMD symptoms are the factors that people with RMDs want to improve when engaging in PA. • The barriers that stop people living with RMDs to do more PA are the ones that can be significantly improved through PA engagement.

Exercise intervention on cardiorespiratory fitness in rheumatoid arthritis patients with high cardiovascular disease risk: a single-arm pilot study.

OBJECTIVE: In patients with rheumatoid arthritis (RA) with cardiovascular disease risk, it is unknown whether exercises are safe, improve cardiorespiratory fitness and reduce disease-related symptoms and cardiovascular-disease (CVD) risk factors. We aimed to investigate in RA patients with CVD risk: (1) safety of medium to high-intensity aerobic exercises, (2) potential changes of cardiorespiratory fitness and (3) disease activity and CVD risk factors in response to the exercises. METHODS: Single-arm pilot-exercise intervention study including 26 consecutive patients (21 women) with > 4% 10-year risk of CVD mortality according to the Dutch Systematic Coronary Risk Evaluation. Aerobic exercises consisted of two supervised-sessions and five home-sessions per week for 12 weeks. Patients were required to exercise at intensities between 65 and 85% of their maximum heart rate. To assess safety, we recorded exercise related adverse events. Before and after the exercises, cardiorespiratory fitness was assessed with a graded maximal oxygen-uptake exercise test, while disease activity was evaluated via the Disease Activity Score-28 (DAS28) using the erythrocyte segmentation rate (ESR). Resting blood pressure, ESR and total cholesterol were assessed as CVD risk factors. RESULTS: Twenty out of 26 patients performed the 12-week exercises without any adverse events. According to patients, withdrawals were unrelated to the exercises. Exercises increased cardiorespiratory fitness (pre: 15.91 vs. post: 18.15 ml.kg-1 min-1, p = 0.003) and decreased DAS28 (pre: 2.86 vs. post: 2.47, p = 0.04). No changes were detected in CVD risk factors. CONCLUSION: A 12-week exercise intervention seems to be safe and improves cardiorespiratory fitness and disease activity in patients with RA with a high risk for cardiovascular diseases. Key Points 1. Rheumatoid arthritis patients with high cardiovascular disease risk were able to perform a maximum exercise test and a 12-week aerobic-based medium-to-high intensity exercise intervention. 2. The exercise intervention improved cardiorespiratory fitness and disease activity in rheumatoid arthritis patients with high cardiovascular disease risk. 3. Cardiorespiratory fitness levels were still low post-exercise intervention (i.e. 18.15 ml.kg-1min-1 compared to the 20.9 ml.kg-1min-1 baseline mean of the RA patients without CVD risk).

Cardiovascular magnetic resonance in autoimmune rheumatic diseases: a clinical consensus document by the European Association of Cardiovascular Imaging.

Autoimmune rheumatic diseases (ARDs) involve multiple organs including the heart and vasculature. Despite novel treatments, patients with ARDs still experience a reduced life expectancy, partly caused by the higher prevalence of cardiovascular disease (CVD). This includes CV inflammation, rhythm disturbances, perfusion abnormalities (ischaemia/infarction), dysregulation of vasoreactivity, myocardial fibrosis, coagulation abnormalities, pulmonary hypertension, valvular disease, and side-effects of immunomodulatory therapy. Currently, the evaluation of CV involvement in patients with ARDs is based on the assessment of cardiac symptoms, coupled with electrocardiography, blood testing, and echocardiography. However, CVD may not become overt until late in the course of the disease, thus potentially limiting the therapeutic window for intervention. More recently, cardiovascular magnetic resonance (CMR) has allowed for the early identification of pathophysiologic structural/functional alterations that take place before the onset of clinically overt CVD. CMR allows for detailed evaluation of biventricular function together with tissue characterization of vessels/myocardium in the same examination, yielding a reliable assessment of disease activity that might not be mirrored by blood biomarkers and other imaging modalities. Therefore, CMR provides diagnostic information that enables timely clinical decision-making and facilitates the tailoring of treatment to individual patients. Here we review the role of CMR in the early and accurate diagnosis of CVD in patients with ARDs compared with other non-invasive imaging modalities. Furthermore, we present a consensus-based decision algorithm for when a CMR study could be considered in patients with ARDs, together with a standardized study protocol. Lastly, we discuss the clinical implications of findings from a CMR examination.

Cardiorespiratory fitness and physical activity in people who have rheumatoid arthritis at an increased risk of cardiovascular disease: a cross-sectional study.

Lower cardiorespiratory fitness (CRF) and physical activity (PA) associate with higher cardiovascular disease (CVD) risk, but the relationship between CRF and PA in people who have rheumatoid arthritis (RA) at an increased CVD risk (CVD-RA) is not known. The objectives of this study were to determine the levels of CRF and PA in people who have CVD-RA and to investigate the association of CRF with PA in people who have CVD-RA. A total of 24 consecutive patients (19 women) with CVD-RA (> 4% for 10-year risk of fatal CVD development as calculated using the Systematic Coronary Risk Evaluation)-were included in the study. CRF was assessed with a graded maximal exercise test determining maximal oxygen uptake (VO2max). PA was assessed with an accelerometer to determine the amount of step count, sedentary, light and moderate-to-vigorous physical activity (MVPA) minutes per day. Mean age of patients was 65.3 ± 8.3 years. CRF mean values were 16.3 ± 1.2 ml·kg-1 min-1, mean step count per day was 6033 ± 2256, and the mean MVPA time was 16.7 min per day. Significant positive associations were found for CRF with step count (B = 0.001, P = 0.01) and MVPA time (B = 0.15, P = 0.02); a negative association was found for CRF with sedentary time (B = - 0.02, P = 0.03). CRF is low and is associated with step count, sedentary time and MVPA time in people who have RA at an increased CVD risk.

Nailfold videocapillaroscopy: a novel possible surrogate marker for the evaluation of peripheral microangiopathy in pulmonary arterial hypertension.

Nailfold videocapillaroscopy (NVC) changes in systemic sclerosis (SSc) are correlated with vascular complications, such as pulmonary arterial hypertension (PAH), supporting a potential link between peripheral and internal organ vasculopathy. The current stage of knowledge regarding NVC and PAH is discussed, focusing on the assessment of peripheral microangiopathy and a potential relationship with functional, echocardiographic, and haemodynamic markers of cardiac dysfunction. A comprehensive literature search was carried out to identify all studies focusing on NVC findings in patients with PAH, diagnosed with right heart catheterization. The majority of the studies examined NVC findings in patients with SSc-PAH, while three studies reported NVC abnormalities in patients with idiopathic PAH. Besides the pulmonary vasculature, a systemic component of microangiopathy seems to be involved in PAH. Well-designed prospective trials are warranted to validate NVC as a biomarker, with clinical implications in the diagnostic evaluation, risk stratification, and overall management of PAH in the daily clinical setting.

Does the intensity of daily walking matter for protecting against the development of a slow gait speed in people with or at high risk of knee osteoarthritis? An observational study.

OBJECTIVE: Knee osteoarthritis (OA) is a risk factor for a decline in gait speed. Daily walking reduces the risk of developing slow gait speed and future persistent functional limitation. However, the protective role of walking intensity is unclear. We investigated the association of substituting time spent not walking, with walking at light and moderate-to-vigorous intensities for incident slow gait over 2-years, among people with or at high risk of knee OA. METHOD: We used baseline and 2-year follow-up data from the Multicenter Osteoarthritis (MOST) study (n = 1731) and the Osteoarthritis Initiative (OAI, n = 1925). Daily walking intensity was objectively assessed using accelerometer-enabled devices, and classified as; not walking (<1 steps/min), very-light (1-49 steps/min), light (50-100 steps/min), and moderate-to-vigorous (>100 steps/min). We defined slow gait during a 20-m walk, as <1 m/s and <1.2 m/s. Isotemporal substitution evaluated time-substitution effects on incident slow gait outcomes at 2-years. RESULTS: Replacing 20 min/day of not walking with walking at a moderate-to-vigorous intensity, demonstrated small to moderate reductions in the risk of developing a gait speed <1.0 m/s (Relative Risk [95% confidence interval (CI)]; MOST = 0.51 [0.27, 0.98], OAI = 0.21 [0.04, 0.98]), and <1.2 m/s (MOST = 0.73 [0.53, 1.00], OAI = 0.65 [0.36, 1.18]). However, only risk reductions for <1.0 m/s met statistical significance. Replacing not walking with very-light or light intensity walking was not associated with the risk of developing slow gait outcomes. CONCLUSION: When possible, walking at a moderate-to-vigorous intensity (>100 steps/min) may be best recommended in order to reduce the risk of developing critical slow gait speed among people with, or at high risk of knee OA.

Accuracy of injection and short-term pain relief following intra-articular corticosteroid injection in knee osteoarthritis - an observational study.

BACKGROUND: Intra-articular corticosteroid injections (IACI) are effective treatments for pain in knee osteoarthritis (KOA) but treatment response varies. There is uncertainty as to whether structural factors such as accurate placement of IACI affect outcome. We examined this question in a pragmatic observational study, using ultrasound (US) to verify accuracy of IACI. METHODS: 105 subjects with KOA (mean age 63.1 years, 59% female) routinely referred for IACI underwent assessment of demographic factors, x-ray and US of the knee before aspiration and IACI (based on clinical landmarks) with 40 mg triamcinolone acetonide with lignocaine plus a small amount of atmospheric air by an independent physician. US demonstration of intra-articular mobile air, i.e. a positive air arthrosonogram, was used to determine accurate placement of injection. Both patients and injecting physicians were blind to the US findings. Pain at baseline, three and nine weeks post injection was assessed using the 500 mm WOMAC pain subscale and response defined as ≥ 40% reduction in pain from baseline. Inter-observer reliability of air-arthrosonogram assessment was good: κ 0.79 (three raters). RESULTS: Sixty-three subjects (60.6%) were responders at three weeks and 43 (45.7%) at nine weeks. Seventy-four subjects (70.5%) had a positive arthrosonogram. A positive air arthrosonogram did not associate with a higher rate of response to treatment (p 0.389 at three weeks, p 0.365 at nine weeks). There was no difference in US effusion depth, power Doppler signal or radiographic grade between responders and non-responders to the injection, but female gender associated with response at 3 weeks and previous injection with non-response at 9 weeks. CONCLUSIONS: Accurate intra-articular injection of corticosteroid results did not result in superior outcome in terms of pain compared to inaccurate injection in symptomatic knee OA.

EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update.

Patients with rheumatoid arthritis (RA) and other inflammatory joint disorders (IJD) have increased cardiovascular disease (CVD) risk compared with the general population. In 2009, the European League Against Rheumatism (EULAR) taskforce recommended screening, identification of CVD risk factors and CVD risk management largely based on expert opinion. In view of substantial new evidence, an update was conducted with the aim of producing CVD risk management recommendations for patients with IJD that now incorporates an increasing evidence base. A multidisciplinary steering committee (representing 13 European countries) comprised 26 members including patient representatives, rheumatologists, cardiologists, internists, epidemiologists, a health professional and fellows. Systematic literature searches were performed and evidence was categorised according to standard guidelines. The evidence was discussed and summarised by the experts in the course of a consensus finding and voting process. Three overarching principles were defined. First, there is a higher risk for CVD in patients with RA, and this may also apply to ankylosing spondylitis and psoriatic arthritis. Second, the rheumatologist is responsible for CVD risk management in patients with IJD. Third, the use of non-steroidal anti-inflammatory drugs and corticosteroids should be in accordance with treatment-specific recommendations from EULAR and Assessment of Spondyloarthritis International Society. Ten recommendations were defined, of which one is new and six were changed compared with the 2009 recommendations. Each designated an appropriate evidence support level. The present update extends on the evidence that CVD risk in the whole spectrum of IJD is increased. This underscores the need for CVD risk management in these patients. These recommendations are defined to provide assistance in CVD risk management in IJD, based on expert opinion and scientific evidence.

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.

Prediction of cardiovascular risk in rheumatoid arthritis: performance of original and adapted SCORE algorithms.

OBJECTIVES: Predictive performance of cardiovascular disease (CVD) risk calculators appears suboptimal in rheumatoid arthritis (RA). A disease-specific CVD risk algorithm may improve CVD risk prediction in RA. The objectives of this study are to adapt the Systematic COronary Risk Evaluation (SCORE) algorithm with determinants of CVD risk in RA and to assess the accuracy of CVD risk prediction calculated with the adapted SCORE algorithm. METHODS: Data from the Nijmegen early RA inception cohort were used. The primary outcome was first CVD events. The SCORE algorithm was recalibrated by reweighing included traditional CVD risk factors and adapted by adding other potential predictors of CVD. Predictive performance of the recalibrated and adapted SCORE algorithms was assessed and the adapted SCORE was externally validated. RESULTS: Of the 1016 included patients with RA, 103 patients experienced a CVD event. Discriminatory ability was comparable across the original, recalibrated and adapted SCORE algorithms. The Hosmer-Lemeshow test results indicated that all three algorithms provided poor model fit (p<0.05) for the Nijmegen and external validation cohort. The adapted SCORE algorithm mainly improves CVD risk estimation in non-event cases and does not show a clear advantage in reclassifying patients with RA who develop CVD (event cases) into more appropriate risk groups. CONCLUSIONS: This study demonstrates for the first time that adaptations of the SCORE algorithm do not provide sufficient improvement in risk prediction of future CVD in RA to serve as an appropriate alternative to the original SCORE. Risk assessment using the original SCORE algorithm may underestimate CVD risk in patients with RA.

Rosuvastatin-Induced Carotid Plaque Regression in Patients With Inflammatory Joint Diseases: The Rosuvastatin in Rheumatoid Arthritis, Ankylosing Spondylitis and Other Inflammatory Joint Diseases Study.

OBJECTIVE: Patients with rheumatoid arthritis (RA) and carotid artery plaques have an increased risk of acute coronary syndromes. Statin treatment with the goal of achieving a low-density lipoprotein (LDL) cholesterol level of ≤1.8 mmoles/liter (≤70 mg/dl) is recommended for individuals in the general population who have carotid plaques. The aim of the ROsuvastatin in Rheumatoid Arthritis, Ankylosing Spondylitis and other inflammatory joint diseases (RORA-AS) study was to evaluate the effect of 18 months of intensive lipid-lowering treatment with rosuvastatin with regard to change in carotid plaque height. METHODS: Eighty-six patients (60.5% of whom were female) with carotid plaques and inflammatory joint disease (55 with RA, 21 with AS, and 10 with psoriatic arthritis) were treated with rosuvastatin to obtain the LDL cholesterol goal. Carotid plaque height was evaluated by B-mode ultrasonography. RESULTS: The mean ± SD age of the patients was 60.8 ± 8.5 years, and the median compliance with rosuvastatin treatment was 97.9% (interquartile range [IQR] 96.0-99.4). At baseline, the median number and height of the carotid plaques were 1.0 (range 1-8) and 1.80 mm (IQR 1.60-2.10), respectively. The mean ± SD change in carotid plaque height after 18 months of treatment with rosuvastatin was -0.19 ± 0.35 mm (P < 0.0001). The mean ± SD baseline LDL cholesterol level was 4.0 ± 0.9 mmoles/liter (154.7 ± 34.8 mg/dl), and the mean reduction in the LDL cholesterol level was -2.3 mmoles/liter (95% confidence interval [95% CI] -2.48, -2.15) (-88.9 mg/dl [95% CI -95.9, -83.1]). The mean ± SD LDL cholesterol level during the 18 months of rosuvastatin treatment was 1.7 ± 0.4 mmoles/liter (area under the curve). After adjustment for age/sex/blood pressure, no linear relationship between a reduction in carotid plaque height and the level of LDL cholesterol exposure during the study period was observed. Attainment of the LDL cholesterol goal of ≤1.8 mmoles/liter (≤70 mg/dl) or the amount of change in the LDL cholesterol level during the study period did not influence the degree of carotid plaque height reduction. CONCLUSION: Intensive lipid-lowering treatment with rosuvastatin induced atherosclerotic regression and reduced the LDL cholesterol level significantly in patients with inflammatory joint disease.

Performance of four current risk algorithms in predicting cardiovascular events in patients with early rheumatoid arthritis.

OBJECTIVE: This study was undertaken to assess the predictive ability of 4 established cardiovascular (CV) risk models for the 10-year risk of fatal and non-fatal CV diseases in European patients with rheumatoid arthritis. METHODS: Prospectively collected data from the Nijmegen early rheumatoid arthritis (RA) inception cohort was used. Discriminatory ability for CV risk prediction was estimated by the area under the receiver operating characteristic curve. Calibration was assessed by comparing the observed versus expected number of events using Hosmer-Lemeshov tests and calibration plots. Sensitivity and specificity were calculated for the cut-off values of 10% and 20% predicted risk. RESULTS: Areas under the receiver operating characteristic curve were 0.78-0.80, indicating moderate to good discrimination between patients with and without a CV event. The CV risk models Systematic Coronary Risk Evaluation (SCORE), Framingham risk score (FRS) and Reynolds risk score (RRS) primarily underestimated CV risk at low and middle observed risk levels, and mostly overestimated CV risk at higher observed risk levels. The QRisk II primarily overestimated observed CV risk. For the 10% and 20% cut-off values used as indicators for CV preventive treatment, sensitivity ranged from 68-87% and 40-65%, respectively and specificity ranged from 55-76% and 77-88%, respectively. Depending on the model, up to 32% of observed CV events occurred in patients with RA who were classified as low risk (<10%) for CV disease. CONCLUSIONS: Established risk models generally underestimate (Systematic Coronary Risk Evaluation score, Framingham Risk Score, Reynolds risk score) or overestimate (QRisk II) CV risk in patients with RA.

Cardiovascular risk factors in women with primary Sjögren's syndrome: United Kingdom primary Sjögren's syndrome registry results.

OBJECTIVE: To determine the prevalence of traditional cardiovascular risk factors using established definitions in a large cohort of clinically well-characterized primary Sjögren's syndrome (SS) patients and to compare them to healthy controls. METHODS: Data on cardiovascular risk factors in primary SS patients and controls were collected prospectively using a standardized pro forma. Cardiovascular risk factors were defined according to established definitions. The prevalence of cardiovascular risk factors in the primary SS group was determined and compared to that in the control group. RESULTS: Primary SS patients had a higher prevalence of hypertension (28­50% versus 15.5­25.6%; P < 0.01) and hypertriglyceridemia (21% versus 9.5%; P = 0.002) than age- and sex-matched healthy controls. Furthermore, a significant percentage (56%) of hypertensive patients expected to be on antihypertensive treatment according to best practice was not receiving it. CONCLUSION: Primary SS patients are more than 2 times more likely to experience hypertension and hypertriglyceridemia than age- and sex-matched healthy controls. Additionally, hypertension is underdiagnosed and suboptimally treated in primary SS.

Circulating levels of TNF-like cytokine 1A correlate with the progression of atheromatous lesions in patients with rheumatoid arthritis.

Interactions between TNF-like Cytokine 1A (TL1A) and its receptors, death receptor-3 (DR3) and decoy receptor-3 (DcR3) may be important in atherogenesis. We hypothesized that dysregulation of this system predicts formation of new atheromatic plaques in rheumatoid arthritis (RA). Forty-five patients were prospectively followed up for 40.5 ± 3.6 months. Serum concentrations of TL1A and DcR3 were measured at baseline and carotid and femoral arteries examined by ultrasound at baseline and at the end of follow-up. Individual serum levels of TL1A correlated with the progression of carotid atheromatic plaque height (Spearman rho = 0.550, p = 0.003). Patients with low TL1A and undetectable DcR3 serum levels at baseline showed significantly fewer newly formed carotid plaques during the next 3.5 years than the remaining patients (P = 0.016). Univariate analysis showed that a "low TL1A/DcR3" immunophenotype predicted a preserved atherosclerosis profile in carotid (P = 0.026), or carotid and/or femoral arteries (P = 0.022). Dysregulated TL1A-induced signaling may be associated with risk for accelerated atherosclerosis in RA.

Predictors of asymmetric dimethylarginine levels in patients with rheumatoid arthritis: the role of insulin resistance.

OBJECTIVE: To determine whether demographic, inflammatory, and metabolic factors predict elevated asymmetric dimethylarginine (ADMA) levels in rheumatoid arthritis (RA). METHOD: A total of 67 RA patients [mean age 56 ± 12 years, median disease duration 8 (3-15) years] were assessed. Routine biochemistry tests, lipid profile, glycaemic profile [glucose, insulin, homeostasis model assessment (HOMA), quantitative insulin sensitivity check index (QUICKI)], and inflammatory markers were measured in all patients. ADMA levels were measured by enzyme-linked immunosorbent assay (ELISA). Regression analyses were performed to identify predictors of ADMA in RA. RESULTS: Regression analysis revealed that HOMA (ß = 0.149, p = 0.003) was an independent predictor of ADMA in RA. From the drug factors, anti-hypertensive medication use was associated with lower ADMA levels (ß = -0.081, p = 0.004). ADMA was not associated with RA disease-related parameters or any of the other cardiovascular risk factors that were assessed. CONCLUSIONS: HOMA, a strong indicator of insulin resistance, seems to be the main predictor of elevated ADMA levels in RA patients; ADMA may reflect an important pathway linking abnormal insulin metabolism with endothelial dysfunction in RA.

Distribution of effusion in knee arthritis as measured by high-resolution ultrasound.

Information about the distribution of effusion within the arthritic knee joint should be considered in selecting an anatomical approach for arthrocentesis. We recorded ultrasound measurements of fluid distribution in the knees of patients attending our clinic for knee injections under ultrasound guidance. In a cross-sectional observational study, we used high-resolution ultrasound (US) to record measurements of maximum fluid depth in the medial, midline and lateral regions of the suprapatellar pouch (SPP) in 46 patients with arthritis attending for routine US-guided injection of the knee. Mean fluid depth [in millimetres, (SD)] was significantly greater in the lateral SPP [9.2 (5.1)] than in the medial [6.5 (4.6)] or the midline [5.9 (3.7)] regions with the knee in relaxed full extension (p < 0.001 for comparison of lateral SPP with both midline and medial SPP). Small effusions were more commonly detected in the lateral SPP than elsewhere. In patients with painful knee arthritis, fluid distributes maximally to the lateral SPP in the extended knee. This has implications regarding the anatomical approach to arthrocentesis that clinicians should choose to perform and teach.

Lack of association between asymmetric dimethylarginine and in vivo microvascular and macrovascular endothelial function in patients with rheumatoid arthritis.

OBJECTIVES: The aim of the present study was to investigate if assymetric dimethylarginine (ADMA) is increased in patients with rheumatoid arthritis (RA) compared to healthy controls and to examine associations between ADMA, RA disease activity and in vivo assessments of microvascular and macrovascular endothelial function. METHODS: Sixty-seven RA patients (age [mean ± standard deviation]: 56 ± 12 years, disease duration median [25th-75th percentile]: 8 [3-15] years, 48 women) and 29 healthy controls (age [mean ± standard deviation]: 42 ± 12, 21 women) underwent assessments of microvascular endothelial function (Laser Doppler imaging with iontophoresis of acetylcholine and sodium-nitroprusside), and macrovascular endothelial function (flow-mediated dilatation and glyceryl-trinitrate-mediated dilatation) as well as arterial stiffness. ADMA levels were measured in contemporary specimens using an immunoassay ELISA kit. RESULTS: ADMA levels were significantly higher (p=0.004) in RA patients compared with healthy controls after adjustment for age (difference=0.088, 95% confidence interval 0.029-0.147). ADMA levels did not correlate with demographic or disease characteristics. No correlation was found between ADMA and microvascular and macrovascular endothelial function or with arterial stiffness. CONCLUSIONS: ADMA levels are increased in patients with RA but there was no significant correlation with in vivo assessments of endothelial function. Further studies are needed to unfold the pathophysiological role of nitric oxide/ADMA pathway derangement in endothelial dysfunction and cardiovascular risk in RA.