Jiayun Shen

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.

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

To compare the bone healing effects of denosumab and alendronate in female rheumatoid arthritis (RA) patients by high‐resolution peripheral quantitative computed tomography.

Targeting inflammation in the prevention of cardiovascular disease in patients with inflammatory arthritis

Patients with inflammatory arthritis have increased risk of cardiovascular diseases (CVDs) compared with the general population. Subclinical carotid atherosclerosis and increased arterial stiffness are also common in these patients, which may serve as surrogate end points for cardiovascular (CV) events in clinical trials. Although exact mechanisms are still unclear, persistent systemic inflammation in patients with inflammatory arthritis may contribute to the development of CVD. Dysregulated innate immunity pathways in these patients may also play a role in accelerating atherosclerosis. During the last decade, effective suppression of inflammation by biological disease-modifying antirheumatic drugs has improved the disease outcome dramatically in patients with inflammatory arthritis. Growing evidence suggests that antitumor necrosis factor (TNF) therapy may prevent CVD in patients with rheumatoid arthritis. Nonetheless, data on non-TNF biologics are limited. Whether anti-TNF therapy may prevent CVD in patients with spondyloarthritis also remained unclear. In this review, we summarized the effect of both anti-TNF and non-TNF biologics on the CV system, including traditional CVD risk factors, endothelial function, arterial stiffness, subclinical atherosclerosis, and clinical CVD in patients with inflammatory arthritis.

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.

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.

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 (β = 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.

Dr. Tam,et al,reply

We thank Haroon, et al for their comments1. Their study demonstrated suboptimal performances of established cardiovascular (CV) risk scores in identifying asymptomatic coronary artery disease as confirmed by coronary computed tomography angiography (CCTA) among patients with psoriatic arthritis (PsA). The results were in line with our study based on carotid subclinical atherosclerosis2. However, they found that a multiplication factor of 1.5 accurately categorizes PsA patients as having a high risk of CV diseases, presumably based on the presence of coronary atherosclerosis. To address whether this also applies to our cohort of patients with PsA, we have performed posthoc … Address correspondence to Dr. L.S. Tam, Department of Medicine and Therapeutics, The Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong. E-mail: lstam{at}cuhk.edu.hk

Bone Mass, Microstucture And Strength Can Discriminate Vertebral Fracture In Patients on Long-Term Steroid Treatment.

Context Measurement of areal bone mineral density (aBMD) by dual-energy x-ray absorptiometry (DXA) was able to predict fracture risk. High-resolution peripheral quantitative computed tomography (HR-pQCT) yields additional information about volumetric bone mineral density (vBMD), microarchitecture, and strength that may increase our understanding of fracture susceptibility. Objective To ascertain whether vBMD, microarchitecture, and estimated bone strength derived from HR-pQCT can discriminate vertebral fractures in patients with glucocorticoid-induced osteoporosis (GIOP) independent of aBMD. Design A cross-sectional case-control study. Setting Seven regional hospitals in Hong Kong. Patients A total of 110 patients on long-term glucocorticoids with vertebral fracture, determined radiographically, and 110 patients on long-term glucocorticoids without fracture. Main Outcome Measures We assessed vBMD, microarchitecture, and bone strength; aBMD; and fracture risk assessment tool (FRAX). Results Patients with vertebral fracture had lower total vBMD and a thinner cortex at the distal tibia after adjustment for age, sex, and aBMD or FRAX. In the antiresorptive treatment-naive subgroup, patients with vertebral fracture also had lower total vBMD at both the distal radius and the tibia after adjustment for covariates. Lower total vBMD and a thinner cortex were also noticed in the nonosteoporotic or FRAX score of <10% subgroups with vertebral fracture and were also associated with increasing prevalence of vertebral fracture. Conclusion Patients with GIOP and vertebral fracture have a significant reduction in total vBMD and cortical thinning independent of aBMD and FRAX. These changes may help identify high-risk patients in the subgroups currently considered to have low fracture risk as assessed by DXA or FRAX.

FRI0455 All Cardiovascular (CV) Risk Scores Significantly Underestimated Cv Risk Defined by Carotid Ultrasound in Psoriatic Arthritis- Can We Improve Their Performances?

Background Psoriatic arthritis (PsA) is associated with higher cardiovascular (CV) risk. The performances of established CV risk scores for general population in PsA patients have not been fully evaluated yet. Meanwhile, European League Against Rheumatism (EULAR) recommended to introduce a 1.5 multiplication factor to the CV risk scores for certain patients with rheumatoid arthritis. Whether the multiplication factor could improve the performances of the risk scores in PsA is unknown. Objectives To evaluate the performances of different CV risk scores and their EULAR modified versions in detecting high CV risk in PsA patients defined as the presence of subclinical atherosclerosis (SCA) determined by carotid ultrasonography. Methods Four different CV risk scores namely Framingham risk score (FRS), QRISK II, HeartScore and American College of Cardiology and American Heart Association (ACC/AHA) 10-year atherosclerotic cardiovascular disease (ASCVD) and their EULAR recommended modified versions were calculated. Sonographic evaluation measuring carotid intima-media thickness (IMT) and plaque was used to determine SCA. IMT>0.90 mm and/or the presence of plaque were classified as SCA+. Results 162 patients [49.27±11.9 years, male: 95 (58.6%)] underwent carotid ultrasound were recruited. 142, 137, 128 and 118 patients were eligible to calculate FRS, QRISKII, HeartScore and ASCVD, respectively. 69 (34.3%) patients were considered to have high CV risk based on the presence of SCA. The SCA+ patients were significantly older (55±10 vs 45±12 years; p<0.001) and more diabetic [11 (15.9%) vs 12 (12.9%); p<0.001]. They also had higher systolic blood pressure (SBP: 138±25 vs 128±17 mmHg; p=0.003) and total cholesterol (TC: 5.3±0.9 vs 4.9±0.9 mmol/L, p=0.005). All CV risk scores were significantly higher in SCA+ patients (FRS: 17±14 vs 8±8%, p<0.001; QRISKII: 13±9 vs 7±7%, p=0.002; HeartScore: 3±3 vs 1±2%, p=0.001; ASCVD: 14±14 vs 8±8%, p=0.002). Areas under the receiver operating characteristic (ROC) curves discriminating SCA+ for FRS, QRISKII, HeartScore and ASCVD were 0.71 (0.63–0.80, p<0.001), 0.67 (0.58–0.76, p=0.001), 0.67 (0.58–0.77, p=0.001), and 0.67 (0.58–0.77, p=0.001), respectively. 42 (29.6%), 3 (2.2%), 6 (4.7%) and 35 (29.7%) patients were classified as having high CV risk scores according to FRS>10%, QRISK II>20%, HeartScore>5% and ASCVD>7.5%, respectively. By McNemars test, all scores significantly underestimated the risk of SCA+ (all p<0.05, Figure 1a). By applying the EULAR multiplication factor, 55 (38.7%), 14 (10.2%), 7 (5.5%) and 53 (44.9%) patients were reclassified as having high CV risk, respectively. SCA+ risk was still significantly underestimated by the modified QRISKII and HeartScore, but not by the modified FRS (p=0.683) and ASCVD (p=0.885) (Figure 1b). EULAR modification increased the sensitivity of FRS and ASCVD in predicting SCA from 44% to 51%, and from 44% to 55%, respectively. Conclusions All CV risk scores significantly underestimated the risk defined by carotid ultrasonography. EULAR recommended modification improved the sensitivity of FRS and ASCVD to a moderate level. Disclosure of Interest None declared

SAT0532 Tibial Cortical Thickness Measured by High–Resolution Peripheral Quantitative Computed Tomography Discriminates Vertebral Fractures in Patients on Long-Term Glucocorticoids Independent of Areal Bone Mineral Density: Table 1.

Background Glucocorticoid-induced osteoporosis is the commonest cause of secondary osteoporosis and related fracture. The current gold-standard for the diagnosis of osteoporosis is dual x-ray absorptiometry (DXA) that measures areal bone mineral density (aBMD). However, aBMD has a low predictive value for vertebral fracture. High–resolution peripheral quantitative computed tomography (HR-pQCT) allows assessment of volumetric BMD (vBMD) and bone macro/microstructure. Whether HR-pQCT can better predict vertebral fractures in patients on long-term glucocorticoids (GC) compared to DXA remained uncertain. Objectives To determine if peripheral bone parameters evaluated by HR-pQCT can discriminate patients on long-term GC with and without vertebral fracture independent of aBMD. Methods This is an ongoing, cross-sectional study of 1100 rheumatic disease patients on long-term GC to access prevalent vertebral fracture radiographically (Genant semi-quantitative assessment). 110 patients with fracture (fracture group) and 110 patients without fracture (control group) underwent assessment with 1) aBMD using DXA; and 2) vBMD/structural assessment of the non-dominant distal radius and tibia using HR-pQCT. We hereby report the interim results of the first 78 and 77 patients in the fracture and control groups respectively. Results Both groups were matched in gender [female: 63 (81%) vs 59 (77%); p=0.528], disease type [SLE/RA/others: 28 (36%)/27 (35%)/23 (29%) vs 36 (47%)/16 (21%)/25 (32%); p=0.143], and cumulative GC dose (17.3±13.6 vs 20.2±18.1g, p=0.447). Patients in the fracture group were older (62±14 vs 57±11 years, p=0.009), more postmenopausal [50 (79%) vs 37 (63%), p=0.048], of lower body mass index (BMI) (22.7±3.5 vs 24.2±3.4 kg/m2, p=0.010), and more likely to be on vitamin D [53 (68%) vs 35 (45%), p=0.005] and bisphosphonates [19 (24%) vs 6 (8%), p=0.005]. Only 26 (35%) of the vertebral fracture patients were classified as osteoporotic (femoral neck T-score≤2.5). Fracture patients had a lower vBMD and impaired bone architecture compared with controls (Table). In multivariate logistic regression analysis, after adjusting for age, gender, BMI, vitamin D and bisphosphonate use, and aBMD, lower cortical thickness in the distal tibia (odds ratio: 1.38 for per 0.1mm decrease, 95%CI 1.13–1.67; p=0.001) and current use of vitamin D (3.78, 1.47–9.71; p=0.006) were independently associated with vertebral fracture.Table 1. HR-pQCT parameters in patients with and without vertebral fracture Fracture Control Difference (%) p Radius  Total vBMD, mg/cm3 268±77 339±72 −21.0 <0.001  Ct. vBMD, mg/cm3 843±90 899±61 −6.2 <0.001  Ct. thickness, mm 0.69±0.23 0.87±0.20 −20.8 <0.001  Tb. vBMD, mg/cm3 101±43 132±43 −23.5 <0.001  Tb. number, mm–1 1.27±0.42 1.47±0.30 −13.6 0.002 Tibia  Total vBMD, mg/cm3 218±64 273±62 −20.1 <0.001  Ct. vBMD, mg/cm3 798±78 856±62 −6.7 <0.001  Ct. thickness, mm 0.82±0.27 1.09±0.28 −24.9 <0.001  Tb. vBMD, mg/cm3 116±38 140±36 −17.1 <0.001  Tb. number, mm–1 1.36±0.32 1.52±0.27 −10.5 0.002 Ct, Cortical; Tb, Trabecular. Conclusions Our results suggest that skeletal abnormalities in patients with vertebral fracture are much more pronounced than those indicated by DXA. In particular, reduction in cortical thickness may be an important mechanism of vertebral fracture in rheumatic patients on long-term GC. Disclosure of Interest None declared