The relation between the biochemical composition of knee articular cartilage and quantitative MRI: a systematic review and meta-analysis.

OBJECTIVE: Early and non-invasive detection of osteoarthritis (OA) is required to enable early treatment and monitoring of interventions. Some of the earliest signs of OA are the change in proteoglycan and collagen composition. The aim of this study is to establish the relations between quantitative magnetic resonance imaging (MRI) and biochemical concentration and organization in knee articular cartilage. METHODS: A preregistered systematic literature review was performed using the databases PubMed and Embase. Papers were included if quantitative MRI and a biochemical assay or polarized light microscopy (PLM) was performed on knee articular cartilage, and a quantified correlation was described. The extracted correlations were pooled using a random effects model. RESULTS: 21 papers were identified. The strongest pooled correlation was found for delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) vs proteoglycan concentration (r = 0.59). T1ρ relaxation times are inversely correlated to proteoglycan concentration (r = -0.54). A weak correlation between T2 relaxation times and proteoglycans was found (r = -0.38). No correlation between T2 relaxation time and collagen concentration was found (r = -0.02). A heterogeneous set of correlations between T2 relaxation times and PLM were identified, including strong correlations to anisotropy. CONCLUSION: DGEMRIC measures are significantly correlated to proteoglycan concentration. The needed contrast agent is however a disadvantage; the T1ρ sequence was found as a non-invasive alternative. Remarkably, no correlation was found between T2 relaxation times and collagen concentration. T2 relaxation times is related to organization, rather than concentration of collagen fibers. PROSPERO ID: CRD42020168337.

The effect of anti-TNF treatment on body composition and insulin resistance in patients with rheumatoid arthritis.

Given the link between systemic inflammation, body composition and insulin resistance (IR), anti-inflammatory therapy may improve IR and body composition in inflammatory joint diseases. This study assesses the IR and beta cell function in rheumatoid arthritis (RA) patients with active disease compared to osteoarthritis (OA) patients and investigates the effect of anti-TNF treatment on IR, beta cell function and body composition in RA. 28 Consecutive RA patients starting anti-TNF treatment (adalimumab), and 28 age, and sex-matched patients with OA were followed for 6 months. Exclusion criteria were use of statins, corticosteroids, and cardiovascular or endocrine co-morbidity. Pancreatic beta cell function and IR, using the homeostasis model assessment (HOMA2), and body composition, using dual-energy X-ray absorptiometry (DXA) were measured at baseline and 6 months. At baseline, IR [1.5 (1.1-1.8) vs. 0.7 (0.6-0.9), 100/%S] and beta cell function (133% vs. 102%) were significantly (p < 0.05) higher in RA patients with active disease as compared to OA patients. After 6 months of anti-TNF treatment, IR [1.5 (1.1-1.8) to 1.4 (1.1-1.7), p = 0.17] slightly improved and beta cell function [133% (115-151) to 118% (109-130), p <0.05] significantly improved. Improvement in IR and beta cell function was most pronounced in RA patients with highest decrease in CRP and ESR. Our observations indicate that IR and increased beta cell function are more common in RA patients with active disease. Anti-TNF reduced IR and beta cell function especially in RA patients with highest decrease in systemic inflammation and this effect was not explained by changes in body composition.

Prescription patterns of lipid lowering agents among older patients in general practice: an analysis from a national database in the Netherlands.

BACKGROUND: Dutch cardiovascular risk management guidelines state almost every older adult (≥70 years) is eligible for a lipid lowering drug (LLD). However, life expectancy, frailty or comorbidities may influence this treatment decision. OBJECTIVE: investigate how many older adults, according to age, frailty (Drubbel-frailty index) and comorbidities were prescribed LLDs. METHODS: data of 244,328 adults ≥70 years from electronic health records of 415 Dutch general practices from 2011-15 were used. Number of LLD prescriptions in patients with (n = 55,309) and without (n = 189,019) cardiovascular disease (CVD) was evaluated according to age, frailty and comorbidities. RESULTS: about 69% of adults ≥70 years with CVD and 36% without CVD were prescribed a LLD. LLD prescriptions decreased with age; with CVD: 78% aged 70-74 years and 29% aged ≥90 years were prescribed a LLD, without CVD: 37% aged 70-74 years and 12% aged ≥90 years. In patients with CVD and within each age group, percentage of LLD prescriptions was 20% point(pp) higher in frail compared with non-frail. In patients without CVD, percentage of LLD prescriptions in frail patients was 11pp higher in adults aged 70-74 years and 40pp higher in adults aged ≥90 years compared to non-frail. Similar trends were seen in the analyses with number of comorbidities. CONCLUSION: in an older population, LLD prescriptions decreased with age but-contrary to our expectations-LLD prescriptions increased with higher frailty levels.

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.

Full blood count parameters for the detection of asthma inflammatory phenotypes.

BACKGROUND: In asthma, the airway inflammatory phenotype influences clinical characteristics and treatment response. Although induced sputum is the gold standard test for phenotyping asthma, a more accessible method is needed for clinical practice. OBJECTIVE: To investigate whether white blood cell counts and/or their derived ratios can predict sputum eosinophils or neutrophils in uncontrolled asthma. METHODS: This cross-sectional study evaluated 164 treated but uncontrolled asthmatic patients with sputum induction and blood collection. Receiver-operating characteristic (ROC) curves were used to assess the relationship between blood and sputum parameters. RESULTS: There was a significant positive relationship between blood eosinophil parameters and the percentage of sputum eosinophil count. A weak but significant correlation was found between sputum neutrophil percentage and blood neutrophil percentage (r = 0.219, P = 0.005). ROC curve analysis identified that blood eosinophil percentage count was the best predictor for eosinophilic asthma, with an area under the curve (AUC) of 0.907 (P < 0.001). The optimum cut-point for blood eosinophil percentage was 2.7%, and this yielded a sensitivity of 92.2% and a specificity of 75.8%. The absolute blood eosinophil count was also highly predictive with an AUC of 0.898 (P < 0.0001) at a blood eosinophil cut-off of 0.26 × 10(9) /L. The blood eosinophil/lymphocyte ratio (ELR) and eosinophil/neutrophil ratio (ENR) were increased in eosinophilic asthma, and the neutrophil/lymphocyte ratio (NLR) was increased in neutrophilic asthma. Neutrophilic asthma could also be detected by blood neutrophil percentages and NLR, but with less accuracy. CONCLUSIONS AND CLINICAL RELEVANCE: Blood eosinophil counts and derived ratios (ELR and ENR) can accurately predict eosinophilic asthma in patients with persistent uncontrolled asthma despite treatment. Blood neutrophil parameters are poor surrogates for the proportion of sputum neutrophils. Blood counts may be a useful aid in the monitoring of uncontrolled asthma.

Outcomes of an Australian testing programme for epidermal growth factor receptor mutations in non-small cell lung cancer.

BACKGROUND: Molecular characterisation of non-squamous non-small-cell lung cancer (NSCLC) is required to direct optimal treatment. Treatment of NSCLC with inhibitors of epidermal growth factor receptor (EGFR) tyrosine kinase (EGFR-TKI) should be guided by the presence of activating mutations of the EGFR gene. AIM: To gain insight into the rate of testing, the range of tissues samples, test utility and outcome when cost of testing as a barrier to access is removed in the Australian setting. METHODS: In October 2010, a sponsored programme was commenced to gather data on EGFR gene mutation testing in Australia. Partnering laboratories were funded for provision of de-identified results. For participating patients, the programme supported the test charge. Mutation testing was performed using Sanger sequencing of exons 18-21 of the EGFR. RESULTS: Samples 2013 were submitted from 2012 patients. Full sequencing was achieved in 1717 (85%). Failure of full sequencing was more likely in samples derived from fine needle aspiration(FNA) biopsy than tissue biopsy or pleural/pericardial fluid cell blocks OR 3.1 (95% CI 1.9-5.2). There were 359 mutations seen in 337 patients. 14.5% of cases had a classical mutation conferring sensitivity to EGFR-TKI. In addition there was a range of less common mutations - some predicting responses and others of uncertain significance. 1.4% of cases had mutations associated with non-responsiveness to EGFR-TKI. CONCLUSIONS: EGFR gene mutation testing is feasible on local and interstate lung cancer samples. The rate of valid test outcomes is high, but FNA samples are associated with more frequent test failure.

Older patients with nonspecific complaints at the Emergency Department are at risk of adverse health outcomes.

OBJECTIVE: Older adults at the Emergency Department (ED) often present with nonspecific complaints (NSC) such as 'weakness' or 'feeling unwell'. Health care workers may underestimate illness in patients with NSC, leading to adverse health outcomes. This study compares characteristics and outcomes of NSC-patients versus specific complaints (SC) patients. METHODS: Cohort study in patients ≥ 70 years in two Dutch EDs. NSC was classified according to the BANC-study-framework based on the medical history in the ED letter, before additional diagnostics took place. A second classification was performed at the end of the ED visit/hospital admission. Primary outcomes were functional decline, institutionalization, and mortality at 30 days. RESULTS: 26% (n = 228) of a total of 888 included patients presented with NSC. Compared with SC-patients, NSC-patients were older, more frail, and more frequently female. NSC-patients had a higher risk of functional decline and institutionalization at 30 days (adjusted ORs 1.84, 95% CI 1.27 - 2.72, and 2.46, 95% CI 1.51-4.00, respectively), but not mortality (adjusted OR 1.26, 95% CI 0.58 - 2.73). Reclassification to a specific complaint after the ED visit or hospital admission occurred in 54% of NSC-patients. CONCLUSION: NSC occur especially in older, frail female patients and are associated with an increased risk of functional decline and institutionalization, even after adjustment for worse baseline status. In half of the patients, a specific complaint revealed during ED or hospital stay. Physicians at the ED should consider NSC as a red flag needing appropriate observation and evaluation of underlying serious conditions and needs of this vulnerable patient group.

In RA patients without prevalent CVD, incident CVD is mainly associated with traditional risk factors: A 20-year follow-up in the CARRÉ cohort study.

OBJECTIVES: To extend our investigation of cardiovascular diseases (CVD) in rheumatoid arthritis (RA) patients to a follow up of more than 20 years, with a special focus on patients without prevalent CVD. METHODS: The CARRÉ study is an ongoing prospective cohort study on CV endpoints in RA patients. Results were compared to those of a reference cohort (n = 2484) enriched for type 2 diabetes mellitus (DM). Hazard ratios (HR) for RA and DM patients compared to non-RA/-DM controls were calculated with cox proportional hazard models, and adjusted for baseline SCORE1 (estimated 10-year CVD mortality risk based on CV risk factors). RESULTS: 238 RA patients, 117 DM patients and 1282 controls, without prevalent CVD at baseline were included. Analysis of events in these patients shows that after adjustment, no relevant 'RA-specific' risk remains (HR 1.16; 95%CI 0.88 - 1.53), whereas a 'DM-specific' risk is retained (1.73; 1.24 - 2.42). In contrast, adjusted analyses of all cases confirm the presence of an 'RA-specific' risk (1.50; 1.19 - 1.89). CONCLUSIONS: In RA patients without prevalent CVD the increased CVD risk is mainly attributable to increased presence of traditional risk factors. After adjustment for these factors, an increased risk attributable to RA only was thus preferentially seen in the patients with prevalent CVD at baseline. As RA treatment has improved, this data suggests that the 'RA-specific' effect of inflammation is preferentially seen in patients with prevalent CVD. We suggest that with modern (early) treatment of RA, most of the current increased CVD risk is mediated through traditional risk factors.

Subclinical renal dysfunction is independently associated with cardiovascular events in rheumatoid arthritis: the CARRÉ Study.

BACKGROUND: Patients with rheumatoid arthritis (RA) have double the risk of cardiovascular (CV) disease, largely independently of traditional CV risk factors. Renal dysfunction is associated with CV morbidity and mortality in the general population, but data on this association in RA are lacking. OBJECTIVE: To investigate the association between renal function and CV events in RA. METHODS: The CARRÉ Study is an ongoing prospective cohort study of Dutch patients with RA, which records CV events. Glomerular filtration rate (GFR) was estimated with the abbreviated Modification of Diet in Renal Disease formula. Logistic regression determined the association between estimated GFR and the occurrence of CV events. RESULTS: 353 patients were followed for 3 years, and 23 (7%) had a CV event. Patients who had an event had a significantly lower baseline GFR than those who did not (59 vs 79 ml/min, p=0.001). This association remained significant after adjustment for traditional risk factors: in this analysis, a decrease in GFR of 5 ml/min was associated with a 30% (95% CI 7% to 59%) increase in the occurrence of CV events. During follow-up, an unfavourable change in GFR was noted in patients who later had a CV event compared with those who did not. CONCLUSION: These data confirm that, in RA, renal dysfunction is associated with a higher risk of CV disease independently of traditional CV risk factors.

Minced Autologous Chondral Fragments with Fibrin Glue as a Simple Promising One-Step Cartilage Repair Procedure: A Clinical and MRI Study at 12-Month Follow-Up.

OBJECTIVE: The aim of this study was to investigate early radiological and clinical outcome of autologous minced cartilage treatment as a single-step treatment option in patients with a chondral or osteochondral lesion (OCL) in the knee. DESIGN: Eighteen patients with an OCL in the knee were included. Cartilage from healthy-appearing loose bodies and/or the periphery of the defect were minced into small chips and sealed in the defect using fibrin glue. Preoperatively, and at 3 (n = 14) and 12 (n = 18) months follow-up, magnetic resonance imaging (MRI) was performed. The Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) 2.0 score was used to assess the cartilage repair tissue on MRI at 12 months. The International Knee Documentation Score, Knee Injury and Osteoarthritis Outcome Score, EuroQoL-5D, and Visual Analogue Scale pain were collected preoperatively and 12 months after surgery. RESULTS: Three months postoperative, MRI showed complete defect filling in 11 out of 14 patients. Mean MOCART 2.0 score at 12 months was 65.0 ± 18.9 with higher scores for lateral femoral chondral lesions compared to medial femoral chondral lesions (75.8 ± 14.3, 52.5 ± 15.8 respectively, P = 0.02). Clinical and statistical significant improvements were observed in the patient-reported outcome measures at 12 months postoperatively compared to preoperatively. CONCLUSION: Treatment of OCLs using the autologous minced cartilage procedure resulted in good cartilage repair measured by MOCART 2.0. Clinically relevant improvements were observed in the clinical scores. This study suggests autologous minced cartilage as a promising, single-step treatment for OCLs.

7-Tesla MRI Evaluation of the Knee, 25 Years after Cartilage Repair Surgery: The Influence of Intralesional Osteophytes on Biochemical Quality of Cartilage.

OBJECTIVE: To evaluate the morphological and biochemical quality of cartilage transplants and surrounding articular cartilage of patients 25 years after perichondrium transplantation (PT) and autologous chondrocyte transplantation (ACT) as measured by ultra-high-field 7-Tesla (7T) magnetic resonance imaging (MRI) and to present these findings next to clinical outcome. DESIGN: Seven PT patients and 5 ACT patients who underwent surgery on the femoral condyle between 1986 and 1996 were included. Patient-reported outcome measures (PROMs) were assessed by the clinical questionnaires: Knee injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC), and Visual Analogue Scale (VAS) for knee pain. The morphological (MOCART score) and biochemical quality (glycosaminoglycans [GAGs] content and collagen integrity) of cartilage transplants and surrounding articular cartilage were analyzed by 7T MRI. The results of the PT and ACT patients were compared. Finally, a detailed morphological analysis of the grafts alone was performed. RESULTS: No statistically significant difference was found for the PROMs and MOCART scores of PT and ACT patients. Evaluation of the graft alone showed poor repair tissue quality and high prevalence of intralesional osteophyte formation in both the PT and ACT patients. Penetration of the graft surface by the intralesional osteophyte was related to biochemically damaged opposing tibial cartilage; GAG content was significantly lower in patients with an osteophyte penetrating the graft surface. CONCLUSIONS: Both PT and ACT patients have a high incidence of intralesional osteophyte formation 25 years after surgery. The resulting biochemical damage to the opposing tibial cartilage might be dependent on osteophyte morphology.

Lung perfusion and chest wall configuration is altered by glossopharyngeal breathing.

Glossopharyngeal insufflation is used by competitive breath-hold divers to increase lung gas content above baseline total lung capacity (TLC) in order improve performance. Whilst glossopharyngeal insufflation is known to induce hypotension and tachycardia, little is known about the effects on the pulmonary circulation and structural integrity of the thorax. Six male breath-hold divers were studied. Exhaled lung volumes were measured before and after glossopharyngeal insufflation. On two study days, subjects were studied in the supine position at baseline TLC and after maximal glossopharyngeal insufflation above TLC. Tc 99(m) labelled macro-aggregated albumin was injected and a computed tomography (CT) scan of the thorax was performed during breath-hold. Single photon emission CT images determined flow and regional deposition. Registered CT images determined change in the volume of the thorax. CT and perfusion comparisons were possible in four subjects. Lung perfusion was markedly diminished in areas of expanded lung. 69% of the increase in expired lung volume was via thoracic expansion with a caudal displacement of the diaphragm. One subject who was not proficient at glossopharyngeal insufflation had no change in CT appearance or lung perfusion. We have demonstrated areas of hyperexpanded, under perfused lung created by glossopharyngeal insufflation above TLC.

Beneficial effect of 1-year etanercept treatment on the lipid profile in responding patients with rheumatoid arthritis: the ETRA study.

BACKGROUND: Effective anti-inflammatory treatment with tumour necrosis factor α (TNFα) inhibitors may have favourable effects on the lipid profile. Available evidence is derived from short-term studies, and it is not clear whether TNFα inhibitors have a similar effect on the lipid profile in responders and non-responders to the treatment. OBJECTIVES: To investigate the effect of long-term etanercept treatment on the lipid profile in a large sample of patients with rheumatoid arthritis (RA), stratified for European League Against Rheumatism (EULAR) response. METHODS: Between 2004 and 2008, 292 consecutive patients with active RA (DAS28 >3.2) and a new etanercept prescription were included in an observational cohort. Clinical response variables and lipid samples were collected at baseline and after 4 months and 1 year of etanercept treatment. Generalised estimating equation analyses were used to investigate the longitudinal course of lipid levels in relation to clinical response variables. RESULTS: According to the EULAR response criteria, 76% of the patients were good or moderate responders at 4 months, and 85% of the remainder at 1 year. Significant changes in apoA-I (increased by 3.5% (p=0.002) at 4 months and 3.1% (p=0.005) at 1 year) and apoB/apoA-I ratio (decreased by 6.2% (p<0.001) at 4 months and 3.6% (p=0.025) at 1 year) were observed in EULAR responders. No significant differences were observed in EULAR non-responders at all time points. CONCLUSIONS: Treatment with etanercept resulted in a significant and sustained decrease in the apoB/apoA-I ratio in patients with good or moderate EULAR response. This may have a beneficial effect on the cardiovascular risk in patients with RA.

The metabolic syndrome is amplified in hypothyroid rheumatoid arthritis patients: a cross-sectional study.

OBJECTIVES: Rheumatoid arthritis (RA) patients are at increased risk of cardiovascular disease (CVD), which is even more pronounced in hypothyroid RA patients. An unfavourable cardiovascular risk profile conferred by a higher prevalence of the metabolic syndrome (MetS) and a higher Framingham risk score might explain this amplified cardiovascular morbidity. This study compared first, MetS (features) and second, the Framingham 10-year CVD risk in RA patients with hypothyroidism compared with euthyroid RA patients. METHODS: RA patients participating in the CARRE investigation were divided into two groups: hypothyroid and euthyroid RA patients. MetS according to the National Cholesterol Education Program Third Adult Treatment Panel criteria and the Framingham risk score was compared between hypothyroid and non-hypothyroid CVD event-free RA patients. RESULTS: In total, 257 RA patients were included: 236 with RA (91.8%) and 21 with hypothyroid RA (8.2%), respectively. The prevalence of the MetS was significantly higher in hypothyroid RA patients (43%) compared with RA patients (20%). Moreover, female hypothyroid RA patients had a higher Framingham risk score compared with euthyroid RA patients. With RA patients as the reference category, the age and gender-adjusted prevalence odds ratio for the MetS was 3.5 (95% CI 1.3 to 9.1) in hypothyroid RA. CONCLUSIONS: Hypothyroid RA patients, particularly female patients, have a more unfavourable cardiovascular risk profile, reflected by an increased prevalence of the MetS and higher Framingham score, than euthyroid RA patients, suggesting a greater need for cardiovascular risk management in these patients to prevent future CVD events.

Ankylosing spondylitis: a risk factor for myocardial infarction?

OBJECTIVE: To ascertain the prevalence of myocardial infarction (MI) in ankylosing spondylitis (AS) relative to that in the general population. METHODS: A questionnaire was sent to 593 patients with AS, aged between 50 and 75 years and registered at the Jan van Breemen Institute or VU University Medical Centre. A total of 383 (65%) patients with AS returned their questionnaire that covered the primary outcome, (non-fatal) MI. The prevalence of MI was calculated with data from the general population provided by Netherlands Information Network of General Practice databases as reference. RESULTS: The overall prevalence for MI was 4.4% in patients with AS versus 1.2% in the general population, resulting in an age- and gender-adjusted odds ratio of 3.1 (95% CI 1.9 to 5.1) for patients with AS. When non-responders (35%) were considered as non-MI the odds ratio decreased to 1.9 (95% CI 1.2 to 3.2). CONCLUSIONS: These observations indicate that the prevalence of MI is increased in patients with AS.

EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis.

OBJECTIVES: To develop evidence-based EULAR recommendations for cardiovascular (CV) risk management in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA). METHODS: A multidisciplinary expert committee was convened as a task force of the EULAR Standing Committee for Clinical Affairs (ESCCA), comprising 18 members including rheumatologists, cardiologists, internists and epidemiologists, representing nine European countries. Problem areas and related keywords for systematic literature research were identified. A systematic literature research was performed using MedLine, Embase and the Cochrane library through to May 2008. Based on this literature review and in accordance with the EULAR's "standardised operating procedures", the multidisciplinary steering committee formulated evidence-based and expert opinion-based recommendations for CV risk screening and management in patients with inflammatory arthritis. RESULTS: Annual CV risk assessment using national guidelines is recommended for all patients with RA and should be considered for all patients with AS and PsA. Any CV risk factors identified should be managed according to local guidelines. If no local guidelines are available, CV risk management should be carried out according to the SCORE function. In addition to appropriate CV risk management, aggressive suppression of the inflammatory process is recommended to further lower the CV risk. CONCLUSIONS: Ten recommendations were made for CV risk management in patients with RA, AS and PsA. The strength of the recommendations differed between RA on the one hand, and AS and PsA, on the other, as evidence for an increased CV risk is most compelling for RA.

The relationship between disease-related characteristics and conduction disturbances in ankylosing spondylitis.

OBJECTIVES: Ankylosing spondylitis (AS) is associated with an increased cardiovascular (CV) risk. Conduction disturbances (CD) may explain the CV burden, as they are independently associated with cardiac disease. The aim of this study was (i) to determine the prevalence of CD in AS, and (ii) to evaluate the relationship between CD and demographic and AS-related characteristics. METHODS: A rheumatological evaluation assessing demographic and AS-related characteristics and a resting standard 12-lead electrocardiogram (ECG) were performed in 131 consecutive AS patients. RESULTS: A first-degree atrioventricular (AV) block was found in six (4.6%) patients. One (0.8%) patient suffered from a complete right bundle branch block (RBBB) and one (0.8%) patient had a left anterior hemiblock. A prolonged QRS (pQRS) interval was observed in 38 (29.2%) patients, including those with a complete or incomplete BBB. Age, disease duration, and body mass index (BMI) were significantly associated with the PR interval, and male gender, disease duration, and the Bath Ankylosing Spondylitis Metrology Index (BASMI) with the QRS interval. In multivariate analyses, disease duration remained independently associated with both the PR and the QRS intervals. CONCLUSION: Intraventricular CD is highly prevalent in AS, particularly in patients with long-standing disease. Further research is needed to determine whether intraventricular CD contribute to the increased CV risk and long-term CV mortality in AS.

The interplay between inflammation, lipids and cardiovascular risk in rheumatoid arthritis: why ratios may be better.

BACKGROUND: There is abundant evidence that patients with rheumatoid arthritis (RA) are at elevated cardiovascular (CV) risk. The contribution of lipids in general is well recognised, but is as yet unclear in inflammatory diseases such as RA in part because inflammation appears inversely associated with lipid levels in RA. METHODS: The CARRE study is a cohort study of 353 randomly selected RA outpatients followed since their enrollment in 2001-2002. We used data from this cohort to (i) evaluate the relationship at baseline between lipid levels [total cholesterol (TC), high-density lipoprotein (HDL)-cholesterol and the TC:HDLc ratio] and inflammation [by means of C-reactive protein (CRP)]; and (ii) determine the association of baseline TC and TC:HDLc ratio with incident (fatal and non-fatal) CV events. RESULTS: C-reactive protein correlated negatively with TC (r = -0.184, p = 0.002), more so with HDLc (r = -0.327, p = 0.001) and therefore positively with TC:HDLc ratio (r = 0.204, p = 0.001). These associations were most evident when CRP exceeded 10 mg/l. Furthermore, the TC:HDLc ratio, but not TC, was positively related to event risk, again most marked in those with elevated CRP. CONCLUSION: Our observations support use of TC:HDLc ratio rather than TC alone in assessing cardiovascular risk in RA patients, especially in those with high inflammatory activity.

Microvascular function is impaired in ankylosing spondylitis and improves after tumour necrosis factor alpha blockade.

OBJECTIVES: Ankylosing spondylitis (AS) is associated with increased cardiovascular morbidity and mortality. Microvascular function has been linked to several risk factors for cardiovascular disease. Inflammation in AS may cause microvascular dysfunction. To test this, we assessed microvascular function in (a) patients with AS compared to healthy controls and (b) patients with AS before and after 1 month of anti-tumour necrosis factor (TNF)alpha treatment with etanercept. METHODS: A total of 15 consecutive patients with AS, who were scheduled for etanercept treatment according to the Assessment in Ankylosing Spondylitis (ASAS) group guidelines, and 12 healthy controls matched for age and sex, were recruited. Endothelium-dependent and independent vasodilatation in skin were evaluated with laser Doppler fluxmetry after iontophoresis of acetylcholine and sodium nitroprusside, respectively. Videomicroscopy was used to measure recruitment of skin capillaries after arterial occlusion. RESULTS: Compared to healthy controls, patients with AS had impaired endothelium-dependent vasodilatation and capillary recruitment. Following anti-TNFalpha treatment, microvascular function improved significantly for endothelium-dependent vasodilatation (p = 0.03) and capillary recruitment (p = 0.006). A significant correlation was observed between changes in endothelium-dependent vasodilatation and changes in erythrocyte sedimentation rate (ESR) (r = -0.56; p = 0.03). CONCLUSION: Microvascular dysfunction is present in patients with AS with active disease, but improves as inflammation regresses after TNFalpha blockade.

Immunogenicity does not influence treatment with etanercept in patients with ankylosing spondylitis.

BACKGROUND: Immunogenicity, specifically the onset of antibodies against tumour necrosis factor (TNF) blocking agents, seems to play an important role in non-response to treatment with these drugs. OBJECTIVES: To assess the relation of clinical response of ankylosing spondylitis (AS) to etanercept with etanercept levels, and the presence of antibodies to etanercept. METHODS: Patients with AS were treated with etanercept 25 mg twice weekly, according to the international Assessment in Ankylosing Spondylitis (ASAS) working group consensus statement. Sera were collected at baseline and after 3 and 6 months of treatment. Clinical response was defined as a 50% improvement or as an absolute improvement of 2 points on a (0-10 scale) Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score. Functional etanercept levels were measured by a newly developed ELISA, measuring the binding of etanercept to TNF. Antibodies against etanercept were measured with a two-site assay and antigen binding test. Clinical data were used to correlate disease activity with serum etanercept levels. RESULTS: In all, 53 consecutive patients were included. After 3 months of treatment 40 patients (76%) fulfilled the response criteria. Mean etanercept levels were 2.7 mg/litre and 3.0 mg/litre after 3 and 6 months respectively. Characteristics and etanercept levels of responders and non-responders were similar. No antibodies to etanercept were detected with any of the assays. CONCLUSION: Etanercept levels of responders and non-responders were similar and no antibodies to etanercept were detected with any of the assays. This study indicates that etanercept is much less immunogenic compared with the other TNF-blocking agents.