High inflammatory burden predicts cardiovascular events in patients with axial spondyloarthritis: a long-term follow-up study.

Background: Axial spondyloarthritis (axSpA) patients are at higher risk of cardiovascular (CV) disease (CVD) than the general population, partly due to consequences of inflammation or its treatment. But relationship between inflammation in axSpA and cardiovascular events (CVE) is unknown. Objectives: To examine whether inflammatory burden over time can predict CVE independent of baseline CV risk factors in axSpA patients. Design: A cohort analysis was performed in patients who had been recruited since January 2001. The primary outcome was a first CVE occurring between January 2001 and December 2020. Methods: Three CVD risk scores were computed at baseline. The performance of the original and modified (*1.5 multiplication factor) CV risk algorithms were assessed. Time-varying Cox proportional hazard models and Kaplan-Meier survival analysis were used to assess whether inflammatory burden (Bath ankylosing spondylitis disease activity index [BASDAI] and inflammatory markers), nonsteroidal anti-inflammatory drugs (NSAIDs) and disease modifying antirheumatic drugs (DMARDs) can predict the development of first CVE. Results: 463 patients (35 [26-45] years, male: 360 [77.8%]) were recruited. After a median follow-up of 12 (7-19) years, 61 patients (13.2%) experienced a first CVE. Traditional/modified CV risk scores underestimated CV risk. Erythrocyte sedimentation rate (ESR) ⩾ 20 mm/h was associated with a significantly higher risk of CVE during follow-up (HR: 2.07, 95%CI [1.10, 3.98], p = 0.008). Active disease as indicated by a rising BASDAI also showed positive trend towards a higher risk of developing CVE over time. After adjusting for CV risk scores in the multivariable models, high ESR level (ESR ⩾ 20 mm/h) over time remained significantly associated with a higher risk of developing CV events. Conclusion: Increased inflammatory burden as reflected by elevated ESR levels (ESR ⩾ 20) was associated with increased risk of CVE, while the use of NSAIDs and DMARDs were not.

Serum Calprotectin Level Is Independently Associated With Carotid Plaque Presence in Patients With Psoriatic Arthritis.

Background: Whether calprotectin could play a role in augmenting cardiovascular (CV) risk in patients with psoriatic arthritis (PsA) remains uncertain. The aim of this study is to elucidate the association between serum calprotectin level and subclinical atherosclerosis in patient with PsA. Method: Seventy-eight PsA patients (age: 52 ± 10 years, 41 [52.6%] male) without CV disease were recruited into this cross-sectional study. Carotid intima-media thickness (cIMT) and the presence of plaque were determined by high-resolution ultrasound. Calprotectin levels in serum were quantified by enzyme-linked immunosorbent assay. The variables associated with the presence of carotid plaque (CP) were selected from the least absolute shrinkage and selection operator (LASSO) regression analysis. Results: 29/78 (37.2%) of patient had carotid plaque (CP+ group). Serum calprotectin level was significantly higher in the CP+ group (CP- group: 564.6 [329.3-910.5] ng/ml; CP+ group: 721.3 [329.3-910.5] ng/ml, P = 0.005). Serum calprotectin level correlated with PsA disease duration (rho = 0.280, P = 0.013) and mean cIMT (rho = 0.249, P = 0.038). Using LASSO regression analysis, the levels of Ln-calprotectin (OR: 3.38, 95% CI [1.37, 9.47]; P = 0.026) and PsA disease duration (OR: 1.09, 95% CI [1.01, 1.18]; P = 0.013) were screened out from a total of 19 variables. The model in predicting the presence of CP was constructed by Ln-calprotectin and PsA disease duration with an area under the receiver-operating characteristic (ROC) curve of 0.744, (95 CI% [0.59, 0.80], P = 0.037). Conclusion: Serum calprotectin level is associated with the presence of CP in PsA. Further studies are required to confirm whether this pathway is associated with CV events in PsA.

Association of C-reactive protein and non-steroidal anti-inflammatory drugs with cardiovascular events in patients with psoriatic arthritis: a time-dependent Cox regression analysis.

AIMS: Psoriatic arthritis (PsA) is associated with accelerated atherosclerosis due to underlying inflammation. Whether inflammatory burden and drugs used to suppress inflammation over time are associated with cardiovascular (CV) events remained unclear. This study aims to examine the time-varying effect of C-reactive protein (CRP) levels and the use of drugs, including non-steroidal anti-inflammatory drugs (NSAIDs) and disease modifying anti-rheumatic drugs, on the risk of CV events independent of traditional CV risk factors in PsA patients. METHODS: A retrospective cohort analysis was performed in patients with PsA who were recruited from 2008 to 2015 and followed until the end of 2019. The outcome was occurrence of a first CV event. Framingham risk score (FRS) was used to quantify the traditional CV risk. Cox proportional hazard models with time-varying CRP levels and drugs used were analysed to identify the risk factors for CV events in PsA patients. RESULTS: Two hundred patients with PsA [median age: 47.5 (40.0-56.0); male: 119 (59.5%)] were recruited. After a mean follow-up of 8.8 ± 3.8 years, 30 (15%) patients developed a first CV event. The multivariable Cox regression model showed that time-varying CRP level [hazard ratio (HR) 1.02, 95% confidence interval (CI) 1.00-1.04] and NSAIDs exposure (HR 0.38, 95% CI 0.15-0.96) were significantly associated with CV events after adjusting for baseline FRS (HR 5.06, 95% CI 1.84-13.92). CONCLUSION: Increased inflammatory burden as reflected by elevated CRP level was associated with increased risk of CV events, while the risk was significantly reduced with NSAIDs use in PsA patients.

Effects of RANKL inhibition on promoting healing of bone erosion in rheumatoid arthritis using HR-pQCT: a 2-year, randomised, double-blind, placebo-controlled trial.

OBJECTIVE: To evaluate the effects of denosumab on erosion healing at 2-4 metacarpophalangeal (MCP) head as determined by high-resolution peripheral quantitative CT (HR-pQCT) in patients with rheumatoid arthritis (RA) with stable disease. METHODS: This was a randomised, placebo-controlled, double-blind study. Patients with RA with disease activity score 28 joints (DAS28) ≤5.1 were randomised (1:1) to subcutaneous denosumab 60 mg or placebo once every 6 months for 24 months. The primary outcome was erosion healing at MCP 2-4 on HR-pQCT at 12 months. The effects of denosumab on erosion and joint space parameters on HR-pQCT and radiographs, disease activity and health assessment questionnaire-disability index (HAQ-DI) were also examined. RESULTS: At 24 months, HR-pQCT images were analysed in 98 patients. One-third of the patients achieved sustained low disease activity throughout the study. At 12 months, changes in erosion parameters on HR-pQCT were similar between the two groups. At 24 months, new erosions (19% vs 9%, p=0.009) and erosion progression (18% vs 8%, p=0.019) were more common in the placebo group than the denosumab group. Erosion healing was seen in a significantly higher proportion of patients in the denosumab group (20% vs 6%, p=0.045) at 24 months. No significant changes in joint space parameters on HR-pQCT, van der Heijde-Sharp erosion score, DAS28 and HAQ-DI were observed in the two groups at 12 and 24 months. CONCLUSION: Although no differences in erosion parameters were observed at 12 months, denosumab was more efficacious than placebo in erosion repair on HR-pQCT after 24 months. TRIAL REGISTRATION NUMBER: NCT03239080.

The causal effect of interleukin-17 on the risk of psoriatic arthritis: a Mendelian randomization study.

OBJECTIVE: To determine causal associations between genetically predicted TNF-α, IL-12p70 and IL-17 levels and risk of PsA. METHODS: The publicly available summary-level findings from genome-wide association studies (GWAS) was used to identify loci influencing normal physiological concentrations of TNF-α, IL-12p70 and IL-17 (n = 8293) among healthy individuals as exposure and a GWAS for PsA from the UK Biobank (PsA = 900, control = 462 033) as the outcome. A two-sample Mendelian randomization (MR) analysis was performed using the inverse-variance weighted (IVW), weighted median and MR-Egger regression methods. Sensitivity analysis and MR-Egger regression analysis were performed to evaluate the heterogeneity and pleiotropic effects of each variant. RESULTS: Single-nucleotide polymorphisms (SNPs) at genome-wide significance from GWASs on TNF-α, IL-12p70 and IL-17 were identified as the instrumental variables. The IVW method indicated a causal association between increased IL-17 level and risk of PsA (ß = -0.00186 per allele, s.e. = 0.00043, P = 0.002). Results were consistent in the weighted median method (ß = -0.00145 per allele, s.e. = 0.00059, P = 0.014) although the MR-Egger method suggested a non-significant association (ß = -0.00133 per allele, s.e. = 0.00087; P = 0.087). Single SNP MR results revealed that the C allele of rs117556572 was robustly associated with risk of PsA (ß = 0.00210, s.e. = 0.00069, P = 0.002). However, no evidence for a causal effect was observed between TNF-α, IL-12p70, decreased IL-17 levels and risk of PsA. CONCLUSION: Our findings provide preliminary evidence that genetic variants predisposing to higher physiological IL-17 level are associated with decreased risk of PsA.

Comparison of carotid artery ultrasound and Framingham risk score for discriminating coronary artery disease in patients with psoriatic arthritis.

OBJECTIVES: This study aimed to assess the performance of carotid ultrasound (US) parameters alone or in combination with Framingham Risk Score (FRS) in discriminating patients with psoriatic arthritis (PsA) with and without coronary artery disease (CAD). METHODS: Ninety-one patients with PsA (56 males; age: 50±11 years, disease duration: 9.4±9.2 years) without overt cardiovascular (CV) diseases were recruited. Carotid intima-media thickness (cIMT), the presence of plaque and total plaque area (TPA) was determined by high-resolution US. CAD was defined as the presence of any coronary plaque on coronary CT angiography (CCTA). Obstructive-CAD (O-CAD) was defined as >50% stenosis of the lumen. RESULTS: Thirty-five (38%) patients had carotid plaque. Fifty-four (59%) patients had CAD (CAD+) and 9 (10%) patients had O-CAD (O-CAD+). No significant associations between the presence of carotid plaque and CAD were found. However, cIMT and TPA were higher in both the CAD+ and O-CAD+ group compared with the CAD- or O-CAD- groups, respectively. Multivariate logistic regression analysis revealed that mean cIMT was an independent explanatory variable associated with CAD and O-CAD, while maximum cIMT and TPA were independent explanatory variables associated with O-CAD after adjusting for covariates. The optimal cut-offs for detecting the presence of CAD were FRS >5% and mean cIMT at 0.62 mm (AUC: 0.71; sensitivity: 67%; specificity: 76%), while the optimal cut-offs for detecting the presence of O-CAD were FRS >10% in combination with mean cIMT at 0.73 mm (AUC: 0.71; sensitivity: 56%; specificity: 85%). CONCLUSION: US parameters including cIMT and TPA may be considered in addition to FRS for CV risk stratification in patients with PsA.

DAPSA, carotid plaque and cardiovascular events in psoriatic arthritis: a longitudinal study.

OBJECTIVE: To examine whether Disease Activity in Psoriatic Arthritis (DAPSA) reflecting the inflammatory component of psoriatic arthritis (PsA) can predict cardiovascular (CV) events independent of traditional CV risk factors and subclinical carotid atherosclerosis. METHODS: A cohort analysis was performed in patients with PsA who had been followed since 2006. The outcome of interest was first CV event. Four different CV disease (CVD) risk scores and DAPSA were computed at baseline. The presence of carotid plaque (CP) and carotid intima-media thickness (CIMT) was also determined in a subgroup of patients using high-resolution ultrasound. The association between DAPSA, CVD risk scores, CP, CIMT and the occurrence of CV events was assessed using Cox proportional hazard models. RESULTS: 189 patients with PsA (mean age: 48.9 years; male: 104 (55.0%)) were recruited. After a median follow-up of 9.9 years, 27 (14.3%) patients developed a CV event. Higher DAPSA was significantly associated with an increased risk of developing CV events (HR: 1.04, 95% CI (1.01 to 1.08), p=0.009). The association remained significant after adjusting for all CV risk scores in the multivariable models. In the subgroup analysis, 154 patients underwent carotid ultrasound assessment and 23 (14.9%) of them experienced a CV event. CP was associated with increased risk of developing CV events after adjusting for three CV risk scores and DAPSA, with HR ranging from 2.35 to 3.42. CONCLUSION: Higher DAPSA and the presence of CP could independently predict CVD events in addition to traditional CV risk scores in patients with PsA.

Treat to target and prevention of subclinical atherosclerosis in psoriatic arthritis-which target should we choose?

OBJECTIVE: PsA patients who achieved sustained minimal disease activity (sMDA) had less subclinical atherosclerosis progression. The vascular effects of achieving other potential treatment targets, including the PsA Disease Activity Score (PASDAS) and the Disease Activity in PsA (DAPSA) score, remained uncertain. This study aimed to compare the vascular effects of achieving different treatment targets in PsA patients. METHOD: This is a post hoc analysis of a 2 year treat-to-target study aimed at MDA. A total of 101 consecutive PsA patients without overt cardiovascular disease were recruited. High-resolution carotid ultrasound and arterial stiffness markers were assessed annually. Low disease activity (LDA) was defined as MDA, DAPSA ≤14 or PASDAS ≤3.2. Sustained disease control was defined as achieving these targets at each visit from month 12 until month 24. RESULTS: Ninety patients [52 male (57.8%), age 50 years (s.d. 11)] who completed 24 months of follow-up were included in this analysis. A total of 44%, 48% and 45% of patients achieved sustained DAPSA LDA (sDAPDA-LDA), sustained PASDAS LDA (sPASDAS-LDA) and sMDA, respectively. Patients who achieved sMDA had significantly less progression of carotid intima-media thickness than those who did not (P = 0.031). Using multivariate analysis, achieving sMDA and sPASDAS-LDA had a protective effect on plaque progression, less increase in total plaque area, reduced mean intima-media thickness and reduced augmentation index after adjusting for covariates. In contrast, no significant differences in the progression of vascular parameters were demonstrated between patients who did or did not achieve sDAPSA-LDA. CONCLUSION: Achieving sMDA/sDASPAS-LDA, but not sDAPSA-LDA, was associated with a protective effect in subclinical atherosclerosis and arterial stiffness progression. A multidimensional domain of disease control might be better in minimizing cardiovascular risk in PsA.

Progressive structural bone changes and their relationship with treatment in patients with psoriatic arthritis: a longitudinal HR-pQCT study.

BACKGROUND: Although the short-term effects of tumor necrosis factor alpha (TNF-α) and interleukin-17A (IL-17A) inhibition on the structural changes in psoriatic arthritis (PsA) using high-resolution peripheral quantitative computed tomography (HR-pQCT) have been reported, no studies have investigated the long-term structural changes in PsA patients receiving routine care. We reported longitudinal changes of erosions and enthesiophytes using HR-pQCT and their relationship with treatments in PsA patients over a 5-year period. METHODS: HR-pQCT examination at the second and third metacarpal heads (MCH2 and MCH3) was performed in 60 PsA patients at baseline and after 5 years. The size of each individual lesion was quantified. Erosion and enthesiophyte progression were defined as change exceeding the smallest detectable change (SDC). RESULTS: A total of 108 bone erosions and 99 enthesiophytes were detected at baseline. Three new bone erosions but no new enthesiophytes were evident at 5 years. A significant increase in mean (±SD) erosion (0.58 ± 1.50 mm3, P < 0.001) and enthesiophyte (0.47 ± 0.76 mm3, P < 0.001) volume was observed. Erosion and enthesiophyte progression were found in 37/111 (33.3%) and 50/99 (50.5%) lesions, respectively. During this 5-year period, 26 (43%) out of the 60 patients achieved sustained Disease Activity index for PSoriatic Arthritis (DAPSA) low disease activity (LDA) (SDL group, defined as achieving DAPSA-LDA at both baseline and 5 years). Fourteen (23%) out of 60 patients received a TNF inhibitor throughout the 5-year period (TNFi group). Fewer erosions progressed (12/51 [23.5%] vs 25/60 [41.7%], P = 0.047) and the increased in enthesiophyte volume was significantly less (0.28 ± 0.67 vs 0.61 ± 0.80 mm3, P = 0.048) in the SDL group than in the non-SDL group. However, no significant difference between the TNFi and non-TNFi groups was detected in terms of the change in volume or progression of bone erosion and enthesiophyte. CONCLUSION: Damage accrual in terms of bone erosion and enthesiophyte was observed in PsA patients over a period of 5 years despite receiving routine clinical care. Nonetheless, sustained control of disease activity may be able to prevent these bony damages.

Circulating miR-99b-5p as a novel predictor of erosion progression on high-resolution peripheral quantitative computed tomography in early rheumatoid arthritis: A prospective cohort study.

OBJECTIVES: To compare micro RNA (miRNA) expression: (a) between healthy individuals and early rheumatoid arthritis (ERA) patients with and without erosion on high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline; and (b) to explore whether these miRNAs could inform a signature predictive of erosion progression despite treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). METHODS: The second metacarpophalangeal head (MCP2) was scanned by HR-pQCT at baseline and 1 year in 117 ERA patients. We performed global profiling of 377 miRNAs in 10 ERA patients with and without erosion on HR-pQCT at baseline and six healthy controls. Validation of the miRNAs of interest were conducted using TaqMan® quantitative real-time polymerase chain reaction in the validation ERA cohort (n = 117) at baseline. Correlation between the candidate miRNAs and erosion progression over 1 year were also assessed. RESULTS: In the 377 screened miRNAs, 94 (60.6%) miRNAs were upregulated in patients with erosions, with 13 (8.4%) upregulated more than 2-fold. Sixty-one (39.4%) miRNAs were downregulated in patients with erosions, with 6 (3.9%) downregulated more than 2-fold. Expression of miR-143-3p, miR-145-5p and miR-99b-5p were significantly higher in the plasma of ERA patients with erosions compared with those without erosions. Logistic regression analysis revealed that the baseline expression of miR-99b-5p was an independent predictor of erosion progression at month 12 (Exp [B] = 4.257, 95% CI 1.178-15.386, P = 0.027). CONCLUSIONS: Differential expressions of circulating miR-143-3p, miR-145-5p and miR-99b-5p in the plasma of ERA patients may characterize a severe form of the disease. MiR-99b-5p, in particular, may serve as a possible predictor for erosion progression.

Effect of Achieving Minimal Disease Activity on the Progression of Subclinical Atherosclerosis and Arterial Stiffness: A Prospective Cohort Study in Psoriatic Arthritis.

OBJECTIVE: To investigate the effects of achieving minimal disease activity (MDA) on the progression of subclinical atherosclerosis and arterial stiffness in patients with psoriatic arthritis (PsA). METHODS: A total of 101 consecutive patients with PsA were recruited for this prospective cohort study. All patients received protocolized treatment targeting MDA for a period of 2 years. High-resolution carotid ultrasound and arterial stiffness markers were assessed annually. The primary outcome measure was the effect of achieving MDA at 12 months (MDA group) on the progression of subclinical atherosclerosis over a period of 24 months. Secondary objectives were to compare the changes in arterial stiffness markers over 24 months between the MDA and non-MDA groups, as well as the changes in subclinical atherosclerosis and arterial stiffness markers in patients who achieved MDA at each visit from month 12 through month 24 (sustained MDA [sMDA]). RESULTS: Ninety PsA patients (mean ± SD age 50 ± 11 years, 58% male [n = 52]) who completed 24 months of follow-up were included in this analysis. Fifty-seven patients (63%) had achieved MDA at 12 months. Subclinical atherosclerosis and arterial stiffness outcomes were similar between the MDA and non-MDA groups. Forty-one patients (46%) achieved sMDA. As shown by multivariate analysis, achieving sMDA had a protective effect on plaque progression (odds ratio 0.273 [95% confidence interval 0.088-0.846], P = 0.024), and less of an increase in total plaque area, mean intima-media thickness, and augmentation index values after adjustment for covariates. CONCLUSION: Our results support the recommendation that once MDA is achieved, it should ideally be maintained for a prolonged period in order to prevent progression of carotid atherosclerosis and arterial stiffness in patients with PsA.

Effect of treat-to-target strategies on bone erosion progression in early rheumatoid arthritis: An HR-pQCT study.

OBJECTIVES: To investigate the efficacy of two tight-control treatment strategies aimed at simplified disease activity score [SDAI] remission (SDAI ≤ 3.3) compared to DAS28 remission (DAS28 < 2.6) on progression of bone erosions in early rheumatoid arthritis (ERA) patients using high-resolution peripheral quantitative computed tomography (HR-pQCT). METHODS: This was an open-label study in which 80 early RA patients were randomized to receive 1-year of tight-control treatment. Group 1 (n = 37) aimed at SDAI ≤ 3.3 and group 2 (n = 43) aimed at DAS28-CRP < 2.6. The number and size of bone erosions, as well as the bone mineral density (BMD) surrounding bone erosion at the second metacarpophalangeal joint (MCP2), were measured at baseline and 12 months. RESULTS: After 12 months, images were analyzed in 63 patients. Changes in clinical parameters, number and size of bone erosions as well as the BMD surrounding bone erosion between the two treatment groups were similar. Therefore, a post-hoc analysis including all 63 patients was performed to elucidate the independent predictors of erosion progression and repair. Multivariate analysis revealed that not achieving sustained SDAI remission at month 6, 9 and 12 (p = 0.034) and rheumatoid factor >16U (p = 0.021) were independent predictors associated with an increase in erosion volume. Logistic regression analysis showed that achieving sustained SDAI remission (p = 0.043) was associated with partial erosion repair. CONCLUSIONS: Although more stringent treatment target did not notably affect clinical treatment outcome and erosion progression at 1 year, achieving sustained SDAI remission was found to be associated with partial erosion repair.

Underestimation of Risk of Carotid Subclinical Atherosclerosis by Cardiovascular Risk Scores in Patients with Psoriatic Arthritis.

OBJECTIVE: To test the performances of established cardiovascular (CV) risk scores in discriminating subclinical atherosclerosis (SCA) in patients with psoriatic arthritis. METHODS: These scores were calculated: Framingham risk score (FRS), QRISK2, Systematic COronary Risk Evaluation (SCORE), 10-year atherosclerotic cardiovascular disease risk algorithm (ASCVD) from the American College of Cardiology and the American Heart Association, and the European League Against Rheumatism (EULAR)-recommended modified versions (by 1.5 multiplication factor, m-). Carotid intima-media thickness > 0.9 mm and/or the presence of plaque determined by ultrasound were classified as SCA+. RESULTS: We recruited 146 patients [49.4 ± 10.2 yrs, male: 90 (61.6%)], of whom 142/137/128/118 patients were eligible to calculate FRS/QRISK2/SCORE/ASCVD. Further, 62 (42.5%) patients were SCA+ and were significantly older, with higher systolic blood pressure and higher low-density lipoprotein cholesterol (all p < 0.05). All CV risk scores were significantly higher in patients with SCA+ [FRS: 7.8 (3.9-16.5) vs 2.7 (1.1-7.8), p < 0.001; QRISK2: 5.5 (3.1-10.2) vs 2.9 (1.2-6.3), p < 0.001; SCORE: 1 (0-2) vs 0 (0-1), p < 0.001; ASCVD: 5.6 (2.6-12.4) vs 3.4 (1.4-6.1), p = 0.001]. The Hosmer-Lemeshow test revealed moderate goodness of fit for the 4 CV scores (p ranged from 0.087 to 0.686). However, of the patients with SCA+, those identified as high risk were only 44.1% (by FRS > 10%), 1.8% (QRISK2 > 20%), 10.9% (SCORE > 5%), and 43.6% (ASCVD > 7.5%). By applying the EULAR multiplication factor, 50.8%/14.3%/14.5%/54.5% of the patients with SCA+ were identified as high risk by m-FRS/m-QRISK2/m-SCORE/m-ASCVD, respectively. EULAR modification increased the sensitivity of FRS and ASCVD in discriminating SCA+ from 44% to 51%, and 44% to 55%, respectively. CONCLUSION: All CV risk scores underestimated the SCA+ risk. EULAR-recommended modification improved the sensitivity of FRS and ASCVD only to a moderate level.

Increased prevalence of coronary plaque in patients with psoriatic arthritis without prior diagnosis of coronary artery disease.

OBJECTIVES: To evaluate coronary atherosclerosis in patients with psoriatic arthritis (PsA) and control subjects using coronary CT angiography (CCTA). METHODS: Ninety consecutive patients with PsA (male: 56(62.2%); 50.3±11.1 years) were recruited. 240 controls (male: 137(57.1%); 49.6±10.7 years) without known cardiovascular (CV) diseases who underwent CCTA due to chest pain and/or multiple CV risk factors were recruited for comparison. RESULTS: Patients with PsA and controls were matched in age, gender and traditional CV risk factors (all p>0.2). The prevalence of overall plaque (54(60%)/84(35%), p<0.001), calcified plaque (CP) (29(32%)/40(17%), p=0.002), mixed plaque (MP) (20(22%)/18(8%), p<0.001), non-calcified plaque (NCP) (39(43%)/53(22%), p<0.001) and combined MP/NCP (46(51%)/62(26%), p<0.001) were all significantly higher in patients with PsA. Three-vessel disease was diagnosed in 12(13%) patients with PsA and 7(3%) controls (p<0.001), while obstructive plaques (>50% stenosis) were observed in 8(9%) patients with PsA and 7(3%) controls (p=0.033). After adjusting for traditional CV risk factors, PsA remained an independent explanatory variable for all types of coronary plaques (OR: 2.730 to 4.064, all p<0.001). PsA was also an independent explanatory variable for three-vessel disease (OR: 10.798, p<0.001) and obstructive plaque (3.939, p=0.024). In patients with PsA, disease duration was the only disease-specific characteristic associated with more vulnerable plaques (MP/NCP) in multivariate analysis (1.063, p=0.031). The other independent explanatory variables were age ≥55 years (5.636, p=0.005) and male gender (8.197, p=0.001). CONCLUSIONS: Patients with PsA have increased prevalence, burden and severity of coronary atherosclerosis as documented by CCTA. Longer disease duration was independently associated with the presence of vulnerable MP/NCP plaques in patients with PsA. TRIAL REGISTRATION NUMBER: NCT02232321.

Repair of Bone Erosion in Rheumatoid Arthritis by Denosumab: A High-Resolution Peripheral Quantitative Computed Tomography Study.

OBJECTIVE: To compare the bone healing effects of denosumab and alendronate in female rheumatoid arthritis (RA) patients by high-resolution peripheral quantitative computed tomography. METHODS: This is a post hoc analysis of a randomized controlled trial. Forty patients were randomized in a 1:1 ratio to receive either subcutaneous denosumab (60 mg) once or oral alendronate (70 mg) weekly for 6 months. The size of individual bone erosions and the presence and extent of erosion-associated sclerosis (marginal osteosclerosis) were measured in the second metacarpal head of the nondominant hand at baseline, 3 months, and 6 months. RESULTS: Forty-two erosions were identified at baseline. After 6 months, the width, depth, and volume of erosion significantly decreased in the denosumab group (-0.23 mm, -0.16 mm, -0.91 mm3 , respectively; all P < 0.01), whereas these parameters significantly increased in the alendronate group (0.19 mm, 0.32 mm, and 1.38 mm3 , respectively; all P < 0.01; between-group differences, P < 0.01 for all). Quantitative analysis showed that the bone mineral density of the erosion margin significantly increased only after treatment by denosumab (19.75 mg/cm3 ; P < 0.05 for denosumab, and -5.44 mg/cm3 ; P = 0.51 for alendronate; P < 0.05 for between-group differences). CONCLUSION: Inhibition of receptor activator of NF-κB ligand by denosumab can induce partial repair of erosions in patients with RA, while erosions continued to progress in patients treated with alendronate. Combining denosumab with disease-modifying antirheumatic drugs may be considered for RA patients with progressive bone erosions.

Carotid plaque and bone density and microarchitecture in psoriatic arthritis: the correlation with soluble ST2.

Psoriatic arthritis (PsA) patients have increased risk of both atherosclerosis and osteoporosis. Previous studies revealed that IL-33/ST2 axis may be related to both conditions; however, these associations were never evaluated in a single patients' group. Here we explored the association among plasma levels of IL-33 and its decoy receptor soluble ST2 (sST2), carotid plaque determined by ultrasound, and volumetric bone mineral density (vBMD)/microstructure of distal radius measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) in 80 PsA patients (55% male; 53.0 ± 10.1 years). Plasma sST2 levels were significantly higher in 33 (41%) patients with carotid plaques (11.2 ± 4.5 vs 7.7 ± 3.7 ng/ml, P < 0.001). In multivariate analysis, sST2 was an independent explanatory variable associated with carotid plaques (OR = 1.296, 95% CI: [1.091,1.540]; P = 0.003). After adjustment for the osteoporotic risk factors, sST2 was significantly associated with higher cortical porosity (ß = 0.184, [0.042,0.325]; P = 0.012) and cortical pore volume (2.247, [0.434,4.060]; P = 0.016); and had a trend to be associated with lower cortical vBMD (-2.918, [-6.111,0.275]; P = 0.073). IL-33 was not associated with carotid plaque or vBMD/microstructure. In conclusion, plasma sST2 levels were independently correlated with both carotid plaque and compromised cortical vBMD/microstructure in PsA patients. IL-33/ST2 axis may be a link between accelerated atherosclerosis and osteoporosis in PsA.

A pilot evaluation of Arthritis Self-Management Program by lay leaders in patients with chronic inflammatory arthritis in Hong Kong.

The objectives of this paper are to evaluate the efficacy of a community-based lay-led Arthritis Self-Management Program (ASMP) among patients with chronic inflammatory arthritis and evaluate the effectiveness of "shared care collaboration" between hospital and community. We trained 17 lay leaders and recruited patients with chronic inflammatory arthritis via a new shared-care model between hospital rheumatology centers and community organizations. Participants were allocated to interventional group or a wait list control group. Evaluations were completed before, after (6 weeks), and 3 months after ASMP. We performed analysis of covariance with adjustment with age, sex, marital status, education, employment, duration of illness, and disability at baseline. A total of 65 participants and 32 controls completed the study. The mean (SD) age and duration of illness were 52.0 (11.4) and 5.6 (7.3) years, 90.7 % were female, 80.4 % had rheumatoid arthritis; 25.8, 53.6, and 12.4 % referrals were from hospitals, community organizations, and patient self-help groups, respectively. The interventional group had significantly less pain (p = 0.049 at 6 weeks), used more cognitive coping methods (p = 0.008 at 6 weeks, p = 0.041 at 3 months) and practiced more aerobic exercise (p = 0.049 at 6 weeks, p = 0.008 at 3 months) after adjustment of covariance. The interventional group had a trend of improvement in self-efficacy, fatigue, self-rated health, and health distress. A community-based lay-led ASMP showed positive beneficial effects on participants with chronic inflammatory arthritis. Shared-care collaboration between hospitals, community organizations, and patient self-help groups was demonstrated.

Cumulative inflammatory burden is independently associated with increased arterial stiffness in patients with psoriatic arthritis: a prospective study.

INTRODUCTION: The aim of this study was to examine whether the cumulative inflammatory burden is associated with an increase in arterial stiffness in a prospective cohort of psoriatic arthritis (PsA) patients. METHODS: In total, 72 PsA patients were followed for a median of 6.5 years. Cumulative inflammatory burden was represented by the cumulative averages of repeated measures of erythrocyte sedimentation rate (ca-ESR) and C-reactive protein (ca-CRP). Brachial-ankle pulse wave velocity (PWV) was measured at the last visit. We also included 47 healthy controls for PWV assessment. RESULTS: PWV was significantly higher in PsA patients compared with healthy controls after adjustment for age, gender and body weight (1466±29 cm/s versus 1323±38 cm/s, P=0.008). PsA patients were divided into two groups based on whether their PWV value is ≥1450 cm/s (High PWV group, N=38) or <1450 cm/s (Low PWV group, N=34). The High PWV group had a significantly higher ca-ESR (29 (19 to 44) versus 18 (10 to 32) mm/1st hour, P=0.005) and ca-CRP (0.7 (0.3 to 1.4) versus 0.4 (0.2 to 0.7) mg/dl, P=0.029). Using regression analysis, high ca-ESR (defined as ≥75th percentile: 37 mm/1st hour) was associated with a higher likelihood of being in the High PWV group (odds ratio (OR): 9.455 (1.939 to 46.093), P=0.005, adjusted for baseline clinical and cardiovascular risk factors; and 9.111 (1.875 to 44.275), P=0.006, adjusted for last visit parameters). CONCLUSIONS: Cumulative inflammatory burden, as reflected by ca-ESR, was associated with increased arterial stiffness in PsA patients even after adjustment for cardiovascular risk factors, emphasizing the important role of chronic inflammation in accelerating the development of cardiovascular risks in PsA patients.

IL-33 and soluble ST2 levels as novel predictors for remission and progression of carotid plaque in early rheumatoid arthritis: A prospective study.

OBJECTIVES: To study the association between the baseline IL-33 and soluble ST2 (sST2) levels with disease remission and progression of carotid atherosclerosis in early rheumatoid arthritis (ERA) patients. METHODS: A total of 98 ERA patients were enrolled. Disease activity and the presence of carotid plaque were evaluated at baseline and 12 months later. Plasma IL-33 and sST2 levels were determined using enzyme-linked immunosorbent assay kits. RESULTS: Baseline IL-33 and sST2 levels were associated with inflammatory markers and cardiovascular (CV) risk factors. Overall, 44(45%), 18(18%), and 21(21%) patients achieved remission based on 28-joint disease activity score (DAS28), Boolean, and simplified disease activity score (SDAI) criteria at 12 months, respectively. Patients with detectable IL-33 at baseline were less likely to achieve DAS28 (P = 0.010) and SDAI remission (P = 0.021), while a lower baseline sST2 level was able to predict DAS28, Boolean, and SDAI remission (P = 0.005, 0.001, and <0.001, respectively). Using multivariate analysis, a lower baseline sST2 level independently predict Boolean (OR = 0.789; P = 0.005) and SDAI remission (0.812; P = 0.008). Regarding carotid atherosclerosis, 9/98(9.2%) patients had plaque progression at 12 months. Baseline IL-33 was detectable in 8/9(89%) and 42/83(51%) of patients with and without plaque progression respectively (P = 0.029). Baseline detectable IL-33 was an independent predictor for plaque progression after adjusting for traditional CV risk factors (P = 0.017). CONCLUSIONS: Lower baseline sST2 levels independently predict disease remission and baseline detectable IL-33 independently predicts carotid plaque progression in ERA patients. This study suggests that inflammation induced by the IL-33/ST2 axis may play a significant role in the development of cardiovascular disease in RA.

Dynamic contrast-enhanced imaging of the wrist in rheumatoid arthritis: dedicated low-field (0.25-T) versus high-field (3.0-T) MRI.

OBJECTIVE: To compare the assessment of wrist synovitis severity, synovial volume and synovial perfusion parameters on a dedicated low-field (0.25-T) to that of a high-field (3-T) whole-body MR system in patients with rheumatoid arthritis (RA). METHODS: Twenty-one patients (mean age 50.0 ± 9.8 years) with active RA were recruited prospectively. Dynamic contrast-enhanced MRI examination of the most severely affected wrist was performed at both 0.25 T and 3 T. Three MRI-derived parameters, synovitis severity (RAMRIS grade), synovial volume (ml(3)) and synovial perfusion indices (maximum enhancement and enhancement slope), were compared. RESULTS: Comparing 0.25- and 3-T MRI, there was excellent agreement for semiquantitative assessment (r: 0.80, p < 0.00001) of synovitis (RAMRIS) as well as quantitative assessment (r: 0.94, p < 0.00001) of synovial volume. Good agreement for synovial Emax (r: 0.6, p = 0.002) and fair agreement (r: 0.5, p = 0.02) for synovial Eslope was found. CONCLUSIONS: Imaging of the RA wrist at 0.25 T yields excellent correlation with 3 T with regard to the synovitis activity score (RAMRIS) and synovial volume measurement. Fair to good correlation between low- (0.25-T) and high-field (3-T) MR systems was found for perfusion parameters, being better for Emax than for Eslope.