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).

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.

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.

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.

What predicts obesity in patients with rheumatoid arthritis? An investigation of the interactions between lifestyle and inflammation.

OBJECTIVE: To assess whether physical activity, diet or inflammation is a more important determinant of body mass index (BMI) and body fat (BF) in patients with rheumatoid arthritis (RA). METHODS: A total of 150 RA patients (102 female) were assessed for BMI and BF. Their habitual physical activity was assessed with the international physical activity questionnaire (IPAQ) and their energy intake with a 3-day food diary. Pro-inflammatory cytokines (interleukins, IL-1 and IL-6, and tumor necrosis factor-alpha), erythrocyte sedimentation rate, C-reactive protein, disease activity score-28 and physical function (Health Assessment Questionnaire-HAQ) were also measured. RESULTS: BMI correlated inversely with IPAQ (r=-0.511, P=0.000) and positively with energy intake (r=0.331, P=0.016) and HAQ (r=0.133, P=0.042). BF correlated inversely with IPAQ (r=-0.575, P=0.000) and positively with HAQ (r=0.201, P=0.037). Normal weight patients were more physically active compared with those who were either overweight (P=0.006) or obese (P=0.000). Underweight patients consumed significantly fewer calories compared with other patients (P<0.05 in all cases). Cytokines or HAQ did not differ between weight groups. IPAQ was the sole predictor of obesity, whereas energy intake was the sole predictor of underweight. CONCLUSIONS: Inflammation does not seem to influence BMI and BF in RA. As in the general population, high levels of habitual physical activity associate with low BMI and BF in RA. Energy intake is a major determinant of being underweight in those who consume fewer calories. Further research is needed to investigate the suitability of exercise and diet modalities, and their effects on the body composition of RA patients.

Cardiovascular risk factors and not disease activity, severity or therapy associate with renal dysfunction in patients with rheumatoid arthritis.

OBJECTIVES: The present study aimed to evaluate the prevalence and associations of renal dysfunction in patients with rheumatoid arthritis (RA). It specifically addressed the hypotheses that renal dysfunction in these patients may associate with the presence of insulin resistance, dyslipidaemia, uric acid levels and/or current levels of systemic inflammation. METHODS: Renal function was assessed by estimated glomerular filtration rate (GFR) using the modification of diet in renal disease equation in 400 consecutive RA patients for this cross-sectional, single-centre study. Risk factors for renal dysfunction were recorded/measured in all participants. Correlations between GFR and other variables were analysed by Pearson or Spearman test as appropriate. Linear regression was used to test the independence of the associations between GFR and other variables. RESULTS: In this RA patient cohort, 67.75% of patients had a reduced GFR of less than 90 ml/minute per 1.73 m(2) and 12.75% had a GFR of less than 60 ml/minute per 1.73 m(2). Multivariable analysis revealed significant associations between GFR and age (beta = -0.370, p<0.001), female sex (beta = -0.181, p=0.002), total cholesterol (beta = -0.112, p=0.022), serum uric acid (SUA) (beta = -0.425, p<0.001) and the presence of extra-articular disease, apart from sicca and/or nodules (beta = -0.084, p=0.040). CONCLUSIONS: Renal dysfunction in RA is quite common and associates with classic cardiovascular risk factors such as advanced age and dyslipidaemia, levels of SUA and the presence of extra-articular disease. Renal dysfunction was not related to other RA-related factors including disease activity and duration, disability and past or present use of nephrotoxic medications.

Rheumatoid cachexia and cardiovascular disease.

OBJECTIVE: It has been frequently stated that rheumatoid cachexia (RC) associates with increased cardiovascular risk; however, no studies to date have investigated this. The aim of this study was to investigate the association of RC with multiple novel and classical cardiovascular disease (CVD) risk factors and the presence of established CVD in rheumatoid arthritis (RA). METHODS: A total of 34 RA patients with RC (RA+RC) were identified from a database of 400 RA patients using published RC criteria and compared to the remaining patients (RA-RC) who did not fulfil RC criteria. All patients were assessed for fat and fat-free mass, albumin (indicator of catabolism), disease activity/severity, novel and classical risk CVD factors and established CVD. RESULTS: Fat-free mass (kg) and albumin (g/L) were significantly decreased in RA+RC vs. RA-RC patients: 37.3(33.9-41.6) vs. 45.9(41.2-55.5), p<0.001 and 39.6 + or - 6.7 vs. 42.4 + or - 4.9, p=0.001). Percent body fat was not significantly different. No significant differences were detected in either the classical or novel CVD risk factors, 10-year CVD risk or the prevalence of established CVD. CONCLUSIONS: RC does not appear to be associated with worse CVD profile in RA patients, but this needs to be confirmed in prospective studies.

Transforming growth factor-beta1 869T/C, but not interleukin-6 -174G/C, polymorphism associates with hypertension in rheumatoid arthritis.

OBJECTIVES: Part of the deleterious effects of systemic inflammation on the cardiovascular system of patients with RA may be exerted via increased propensity to hypertension. IL-6 and TGF-beta1 are important regulators of the inflammatory response. In some, but not all, studies, IL6 -174G/C (rs1800795) and TGFB1 869T/C (rs1982073) gene polymorphisms have been associated with hypertension in the general population. The present study addressed their potential association with hypertension in RA patients. METHODS: TGFB1 869T/C and IL6 -174G/C were identified in 400 RA patients and 422 local, non-RA controls using real-time PCR and melting curve analysis. Binary logistic and linear regression models were used to identify the independence of the effects of the polymorphisms on hypertension. RESULTS: Genotypic and allelic frequencies of the two polymorphisms were similar in RA and controls. Within the RA group, there was no significant association between IL6 -174G/C and hypertension, but TGF 869T-allele carriers had significantly increased prevalence of hypertension compared with CC homozygotes (70.2 vs 55.2%; P = 0.023). This association remained significant after adjustment for other hypertension risk factors and medication (odds ratio = 1.96; 95% CI 1.02, 3.77; P = 0.044), and was more pronounced in patients with increased systemic inflammation. CONCLUSIONS: This study suggests an association of TGFB1 869T/C, but not of IL6 -174G/C, with hypertension in RA patients. If this finding is confirmed in prospective studies, this polymorphism could be used as a screening tool for RA patients with higher risk of developing hypertension and lead to increased surveillance and earlier treatment.

Associations of obesity with modifiable risk factors for the development of cardiovascular disease in patients with rheumatoid arthritis.

OBJECTIVES: To assess the association of body mass index (BMI) with modifiable cardiovascular disease (CVD) risk factors in patients with rheumatoid arthritis (RA). METHODS: BMI, disease activity, selected CVD risk factors and CVD medication were assessed in 378 (276 women) patients with RA. Patients exceeding accepted thresholds in >or=3 CVD risk factors were classified as having the metabolic syndrome (MetS). RESULTS: BMI independently associated with hypertension (OR = 1.28 (95% CI = 1.22 to 1.34); p = 0.001), high-density lipoprotein (OR = 1.10 (95% CI = 1.06 to 1.15); p = 0.025), insulin resistance (OR = 1.13 (95% CI = 1.08 to 1.18); p = 0.000) and MetS (OR = 1.15 (95% CI = 1.08 to 1.21); p = 0.000). In multivariable analyses, BMI had the strongest associations with CVD risk factors (F(1-354) = 8.663, p = 0.000), and this was followed by lipid-lowering treatment (F(1-354) = 7.651, p = 0.000), age (F(1-354) = 7.541, p = 0.000), antihypertensive treatment (F(1-354) = 4.997, p = 0.000) and gender (F(1-354) = 4.707, p = 0.000). Prevalence of hypertension (p = 0.004), insulin resistance (p = 0.005) and MetS (p = 0.000) was significantly different between patients with RA who were normal, overweight and obese, and BMI differed significantly according to the number of risk factors present (p = 0.000). CONCLUSIONS: Increasing BMI associates with increased CVD risk independently of many confounders. RA-specific BMI cut-off points better identify patients with RA at increased CVD risk. Weight-loss regimens should be developed and applied in order to reduce CVD in patients with RA.

Predictors of fatigue over 1 year among people with rheumatoid arthritis.

Fatigue is a systemic feeling of exhaustion that is a common symptom of many chronic illnesses, including the autoimmune inflammatory disease rheumatoid arthritis (RA). We examined predictors of levels of fatigue among people with RA using Leventhal's Common-Sense Model (CSM), which states that cognitive representations of an illness spur (or halt) people's efforts to cope and thereby influence outcomes of the illness. Our use of the CSM was designed in the light of evidence in the literature specific to fatigue in RA. Current fatigue was reported on a 100 mm visual analogue scale (with anchors "No fatigue" and "Unbearable fatigue") by 114 people (73.7% women) with RA at baseline and 1 year later. Baseline employment status, pain, impact of disability, sleep disruption frequency, depressed mood, perceptions of consequences, arthritis self-efficacy and attempts to cope by praying/hoping were also self-reported. Duration of RA and a haematological measure of systemic inflammation (erythrocyte sedimentation rate; ESR) were obtained from hospital records. Unexpectedly, RA duration did not predict fatigue after 1 year, although lower baseline inflammation did (controlling for baseline fatigue and other disease impact variables). This may be due to sampling flares of RA at baseline. Baseline perceptions that RA has severe consequences and is uncontrollable also predicted greater fatigue after 1 year but this relationship was not mediated by praying/hoping. Targeted psychological care to modify perceptions of severe consequences may therefore improve later fatigue for people with RA even when the condition is longstanding, but the mechanisms of any benefit require further investigation.

The inter-operator variability in measuring waist circumference and its potential impact on the diagnosis of the metabolic syndrome.

OBJECTIVE: The International Diabetes Federation (IDF) has proposed ethnicity specific cut-off values for waist circumference, as an essential criterion for the diagnosis of the metabolic syndrome (MetS). However, before introducing waist circumference measurement as part of the clinical examination, or an obligatory criterion for MetS, it is important to ensure that the measurement is reliable and reproducible. STUDY DESIGN: The inter- and intra-operator variability in measuring waist circumference was assessed in a preliminary study of 10 health professionals and the inter-operator variability in clinical practice was assessed in a study of 102 patients. Repeated measures analysis of variance (ANOVA) was used to assess the significance of the inter- and intra-operator variability. RESULTS: Intra-operator variability was not found to be significant in the preliminary study (F = 0.15, p = 0.764). However, the inter-operator variability was significant in both studies (preliminary: F = 4.16, p<0.001, clinical practice study: F = 14.06, p<0.001). In clinical practice, this could lead to disagreement among operators regarding the presence of central obesity in 9% of the patients. After giving written instructions on how to measure waist circumference, the coefficient of variation was not significantly altered (p = 0.202) but the inter-operator variability lost significance (F = 2.34, p = 0.11), suggesting a reduction in systematic error. CONCLUSIONS: Measuring waist circumference is subject to significant inter-operator variability and could potentially lead to misclassifying patients as having the MetS, or not. Better training of health professionals on how to measure waist circumference properly is needed in order to ensure that patients are not misclassified and that international comparisons of the prevalence of the MetS are reliable.