Circulating Interleukin 17A and Other Inflammatory Proteins May Predict Cardiovascular Disease in Early Rheumatoid Arthritis.

OBJECTIVE: The objective of this study was to investigate the impact of 92 inflammatory proteins on the risk of cardiovascular disease (CVD) in patients with early rheumatoid arthritis (RA). METHODS: This study included consecutive patients with early RA recruited between 1995 and 2002. Stored plasma samples were analyzed for 92 inflammatory proteins. CVD diagnoses were retrieved from national in-patient and cause-of-death registries. Statistical analyses were predesignated as hypothesis-driven or exploratory. For the latter, proteins were selected based on principal component analysis (ie, factor loading > 0.5 within main components). Potential predictors of CVD and coronary artery disease (CAD) were assessed using Cox regression. RESULTS: Data on baseline levels of proteins and CVD were available for 163 patients. As hypothesized, levels of interleukin 17A (IL-17A) were associated with CVD (hazard ratio 1.35, 95% CI 1.02-1.78, adjusted for age, sex, hypertension, diabetes, smoking, and erythrocyte sedimentation rate [ESR]), although not significantly with CAD. Osteoprotegerin (OPG) levels were significantly associated with both outcomes, but only in crude models. No associations were observed for IL-6, tumor necrosis factor, monocyte chemotactic protein-1, or IL-8. In the exploratory analyses, MCP-3 in particular had significant associations with both outcomes in crude models. CONCLUSION: Circulating IL-17A at RA diagnosis predicted future CVD, although we cannot exclude the possibility that this finding is due to multiple testing. The association was independent of traditional CVD risk factors, and of ESR at the time of diagnosis. Further, OPG may be a predictor of CVD. We also identified some novel potential biomarkers for CVD in RA.

Cardiovascular disease risk in early rheumatoid arthritis: the impact of cartilage oligomeric matrix protein (COMP) and disease activity.

BACKGROUND: To investigate whether baseline serum cartilage oligomeric matrix protein (COMP), patient characteristics, traditional cardiovascular disease (CVD) risk factors and disease activity over time predict CVD, in early rheumatoid arthritis (RA). METHODS: This study included patients with early RA (< 12 months disease duration) (n = 233) recruited 1995-2005. Potential predictors of CVD and coronary artery disease (CAD) were assessed using Cox regression. RESULTS: A first ever diagnosis of CVD occurred in 70 patients, and CAD in 52. Age, sex, hypertension and diabetes predicted CVD and CAD. COMP was associated with increased risk of CVD and CAD [crude hazard ratios (HRs) per SD 1.45; 95% CI 1.17-1.80 and 1.51; 95% CI 1.18-1.92, respectively]. When adjusted for age, sex, hypertension, diabetes and ESR, results where similar but did not reach significance [HRs 1.32, 95% CI 0.99-1.74 and 1.35, 95% CI 0.99-1.86]. Baseline disease activity did not independently predict CVD. High DAS28 (> 5.1) at two years was associated with increased risk of subsequent CVD [adjusted HR 2.58; 95% CI 1.10-6.04] and CAD. ESR and CRP at two years as well as cumulative disease activity over 2 years independently predicted CVD and CAD. CONCLUSION: COMP may be a novel predictor of CVD and CAD in RA. Active disease two years after RA diagnosis, as well as cumulative disease activity, was associated with increased risk of CVD and CAD, independent of traditional CVD risk factors. Awareness of the particularly increased CVD risk among difficult to treat patients is important in order to further reduce CVD in RA.

Radiographic damage in early rheumatoid arthritis is associated with increased disability but not with pain-a 5-year follow-up study.

OBJECTIVES: To evaluate how radiographic damage, overall and measured as joint space narrowing score (JSNS) and erosion score (ES), as well as other clinical and laboratory measures, relate to disability and pain in early rheumatoid arthritis (RA). METHODS: An inception cohort of 233 patients with early RA, recruited in 1995-2005, was followed for 5 years. Disability was assessed with the Health Assessment Questionnaire (HAQ), and pain with a visual analogue scale (VAS; 0-100 mm). Radiographs of hands and feet were evaluated using the Sharp-van der Heijde score (SHS), including JSNS and ES. The relation for radiographic scores and other clinical parameters with pain and HAQ were evaluated cross-sectionally by multivariate linear regression analysis and over time using generalized estimating equations. RESULTS: ES was significantly associated with HAQ cross-sectionally at inclusion, after 2 and after 5 years, and over time. Associations for HAQ with SHS and JSNS were weaker and less consistent compared with those for ES. There was no association between radiographic scores and pain at any visit. Both HAQ and pain were associated with parameters of disease activity. The strongest cross-sectional associations were found for the number of tender joints (adjusted p<0.001 at all visits). CONCLUSION: Joint damage was associated with disability already in early RA. Erosions of hands and feet appear to have a greater influence on disability compared with joint space narrowing early in the disease. Pain was associated with other factors than joint destruction in early RA, in particular joint tenderness-suggesting an impact of pain sensitization.

Male Sex Predicts a Favorable Outcome in Early ACPA-Negative Rheumatoid Arthritis: Data From an Observational Study.

OBJECTIVE: The aim of the present study was to investigate whether the relationship between sex and clinical outcomes in early rheumatoid arthritis (RA) varies by autoantibody status. METHODS: Two inception cohorts of consecutive patients with early RA (ie, symptom duration ≤ 12 months) in the southern region of Sweden were investigated. Patients were stratified by anticitrullinated peptide antibody (ACPA) status. The primary outcome was remission (Disease Activity Score in 28 joints [DAS28] < 2.6) at 12 months. Secondary outcomes were remission at 6 months and European Alliance of Associations for Rheumatology good response at 6 and 12 months compared to baseline. In logistic regression models, which were adjusted for age, DAS28 values, and Health Assessment Questionnaire values at baseline, the relationship between sex and clinical outcomes, stratified by ACPA status, was investigated. RESULTS: In total, 426 patients with early RA were included: 160 patients were ACPA negative and 266 patients were ACPA positive. At 12 months, 27.1% (38/140) of females and 24.1% (13/54) of males with ACPA-positive RA achieved DAS28 remission. In ACPA-negative RA, 16.0% (13/81) of females and 48.6% (18/37) of males achieved DAS28 remission at 12 months. Males had higher odds of reaching remission at 12 months in the ACPA-negative patient group (pooled adjusted odds ratio [OR] 4.79, 95% CI 1.97-11.6), but not in the ACPA-positive group (pooled adjusted OR 1.06, 95% CI 0.49-2.30). CONCLUSION: Male sex was associated with better clinical outcomes in ACPA-negative early RA, but not in ACPA-positive early RA. The poor outcomes in females with early seronegative RA suggest that this represents a difficult-to-treat patient group.

Predictors of radiographic erosion and joint space narrowing progression in patients with early rheumatoid arthritis: a cohort study.

BACKGROUND: Radiographic damage in rheumatoid arthritis (RA) includes erosions and joint space narrowing (JSN). Different mechanisms may underlie their development. The objective of this study was to evaluate predictors of these entities separately. METHODS: Consecutive early RA patients (symptom duration ≤12 months) from a defined area (Malmö, Sweden) recruited during 1995-2005 were investigated. Radiographs of hands and feet were scored by a trained reader according to the modified Sharp-van der Heijde score. Fat mass and lean mass distribution were measured at baseline using dual energy x-ray absorptiometry. Potential predictors of erosion and JSN progression from inclusion to the 5-year follow-up were evaluated. RESULTS: Two hundred and thirty-three patients were included. Radiographs at baseline and 5 years were available for 162 patients. The median (interquartile) progression of erosion and JSN scores were 4 (0-8) and 8 (1-16), respectively. Rheumatoid factor (RF) was a robust significant predictor of both erosion and JSN score progression. In adjusted analyses, anti-CCP antibodies predicted erosions while the erythrocyte sedimentation rate was predictive of both outcomes. Smoking and high baseline disease activity (DAS28 > 5.1) predicted progression of erosions. Baseline erosion score was associated with progression of both erosion and JSN progression, while baseline JSN score was predictive only of the progression of JSN. Overweight/obesity (BMI ≥ 25 kg/m2) was a significant negative predictor of JSN score progression (ß = - 0.14, p = 0.018, adjusted for RF, age, baseline JSN score) also when additionally adjusting for ever smoking (p = 0.041). Among female patients, this effect was observed in those of estimated post-menopausal age (> 51 years), but not in younger women. The truncal to peripheral fat ratio was associated with less JSN score progression in women, but not in men. CONCLUSIONS: Overweight RA patients had less JSN progression, independent of smoking status. This effect was seen in particular among older women (mainly post-menopausal), but not younger. Truncal fat was associated with less JSN progression in female patients. Smoking predicted erosion progression, and erosions may precede JSN. BMI and fat distribution may influence cartilage damage in early RA and might be related to hormonal factors.

Smoking, body mass index, disease activity, and the risk of rapid radiographic progression in patients with early rheumatoid arthritis.

BACKGROUND: Identification of risk factors for rapid joint destruction in early rheumatoid arthritis (RA) can be helpful for optimizing treatment, and improving our understanding of destructive arthritis and its mechanisms. The objective of this study was to investigate the relationship between early RA patient characteristics and subsequent rapid radiographic progression (RRP). METHODS: An inception cohort of patients with early RA (symptom duration < 12 months), recruited during 1995-2005 from a defined area (Malmö, Sweden), was investigated. Radiographs of the hands and feet were scored in chronological order according to the modified Sharp-van der Heijde score (SHS), by a trained reader. RRP was defined as an increase of ≥ 5 points in SHS per year. RESULTS: Two hundred and thirty-three patients were included. Radiographs were available from 216 patients at baseline, 206 patients at 1 year, and 171 patients at 5 years. Thirty-six patients (22%) had RRP up to 5 years. In logistic regression models, rheumatoid factor (RF) and anti-cyclic citrullinated peptides (anti-CCP), and increased erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) at baseline, predicted RRP over 5 years. Patients identified as overweight or obese had a significantly reduced risk of RRP up to 5 years (odds ratio (OR) 0.26; 95% confidence interval (CI) 0.11-0.63; adjusted for RF, baseline erosions, and ESR). Similar point estimates were obtained when stratifying for antibody status, and in models adjusted for smoking. A history of ever smoking was associated with a significantly increased risk of RRP up to 5 years, independent of body mass index (BMI) (OR 3.17; 95% CI 1.22-8.28; adjusted for BMI). At the 1-year follow-up, erosive changes, Disease Activity Score of 28 joints, Health Assessment Questionnaire, swollen joint count, and patient's global assessment of disease activity and pain were also significantly associated with RRP up to 5 years. CONCLUSIONS: A history of smoking, presence of RF and/or anti-CCP and early erosions, high initial disease activity and active disease at 1 year, all increase the risk of RRP. Patients with a high BMI may have a reduced risk of severe joint damage. This pattern was not explained by differences in disease activity or antibody status. The results of this study suggest independent effects of smoking and BMI on the risk of RRP.

Triple antithrombotic therapy following an acute coronary syndrome: prevalence, outcomes and prognostic utility of the HAS-BLED score.

AIMS: The aim of this study was to evaluate the prevalence of triple antithrombotic therapy (TT) (warfarin, aspirin and clopidogrel) in patients following an acute coronary syndrome (ACS), the bleeding risk compared to double antiplatelet therapy (DAPT) (aspirin and clopidogrel) and evaluate the accuracy of the HAS-BLED risk score in predicting serious bleeding events in TT patients. METHODS AND RESULTS: We retrospectively identified all ACS patients on TT upon discharge from the Coronary Care Unit at Skane University Hospital between 2005 and 2010. TT patients were compared to age- and sex-matched control patients discharged with DAPT. Major bleeding was defined in accordance with the HAS-BLED derivation study. A total of 2,423 patients were screened, of whom 159 (6.6%) were on TT. The mean age was 67.2 (±0.9) years. The most common indication for TT was atrial fibrillation (n=63, 39.6%) followed by apical akinesia (n=60, 37.8%), and the mean duration of TT was 3.7 (±0.3) months. Upon termination of TT, warfarin was discontinued in 82 (52.2%) patients and clopidogrel in 57 (36.3%) patients. The cumulative incidence of spontaneous bleeding events was significantly higher with TT compared to DAPT at one year (10.2% vs. 3.2%; p=0.01). The HAS-BLED score significantly predicted spontaneous bleeding events in TT patients (area under the receiver operating characteristic [ROC] curve 0.67; 95% CI=0.54-0.79; p=0.048). CONCLUSIONS: TT was relatively common following acute coronary syndrome and was associated with a threefold increase in major bleeding compared to DAPT at one year. The HAS-BLED risk score predicted bleeding events with moderate accuracy.