Cardiovascular organ damage in relation to hypertension status in patients with ankylosing spondylitis.

PURPOSE: Hypertension is a major cardiovascular (CV) risk factor in ankylosing spondylitis (AS) patients. Less is known about the prevalence of CV organ damage in relation to hypertension status in AS patients. MATERIALS AND METHODS: CV organ damage was assessed by echocardiography, carotid ultrasound and pulse wave velocity (PWV) by applanation tonometry in 126 AS patients (mean age 49 ± 12 years, 39% women) and 71 normotensive controls (mean age 47 ± 11 years, 52% women). CV organ damage was defined as presence of abnormal left ventricular (LV) geometry, LV diastolic dysfunction, left atrial (LA) dilatation, carotid plaque or high pulse wave velocity (PWV). RESULTS: Thirty-four percent of AS patients had hypertension. AS patients with hypertension were older and had higher C-reactive protein (CRP) levels compared to AS patients without hypertension and controls (p < 0.05). The prevalence of CV organ damage was 84% in AS patients with hypertension, 29% in AS patients without hypertension and 30% in controls (p < 0.001). In multivariable logistic regression analyses, having hypertension was associated with a fourfold increased risk of CV organ damage independent of age, presence of AS, gender, body mass index, CRP, and cholesterol (odds ratio (OR) 4.57, 95% confidence interval (CI) 1.53 to 13.61, p = 0.006). In AS patients, presence of hypertension was the only covariable significantly associated with presence of CV organ damage (OR 4.40, 95% CI 1.40 to 13.84, p = 0.011). CONCLUSIONS: CV organ damage in AS was strongly associated with hypertension, pointing to the importance of guideline-based hypertension management in AS patients.

What is the context? Ankylosing spondylitis (AS) is an inflammatory disease primarily affecting the spine. Patients with AS have increased risk for cardiovascular disease. High blood pressure (hypertension) is both very common in AS patients, and a major risk factor for developing cardiovascular disease. Hypertension leads to structural and functional changes in the heart and arteries, referred to as cardiovascular organ damage. However, little is known about the prevalence of cardiovascular organ damage in AS patients with hypertension.What is new? Using ultrasound and tonometry, we assessed organ damage in the heart and arteries in AS patients with hypertension and compared them to AS patients with normal blood pressure as well as a group of healthy controls. We found that 84% of the AS patients with hypertension had cardiovascular organ damage, compared to 29% of AS patients with normal blood pressure and 30% of controls. Independent of other risk factors, hypertension was associated with a fourfold increased risk of cardiovascular organ damage in AS patients.What is the impact? These findings are important because cardiovascular organ damage is potentially reversible with treatment. Our results underline the significance of guideline-directed hypertension management in AS patients to reduce cardiovascular disease.

All-cause and cause-specific mortality in rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis: a nationwide registry study.

OBJECTIVES: To explore mortality and causes of death among Norwegian patients with RA, PsA and axial spondyloarthritis (axSpA) compared with the general population by conducting a nationwide registry-based cohort study. METHODS: Patients with RA, PsA and axSpA were identified from the Norwegian Patient Registry based on ICD-10 codes between 2008 and 2017. Using age as the time variable, all-cause and cause-specific mortality were estimated between 2010 and 2017 with the Kaplan-Meier estimator and the cumulative incidence competing risk method, respectively. Sex-, education level-, health region- and age group-adjusted hazard ratios (HRs) for mortality were estimated using Cox regression models. RESULTS: We identified 36 095 RA, 18 700 PsA and 16 524 axSpA patients (70%, 53% and 45% women, respectively). RA and axSpA were associated with increased all-cause mortality (HR 1.45 [95% CI: 1.41, 1.48] and HR 1.38 [95% CI: 1.28, 1.38], respectively). Women but not men with PsA had a slightly increased mortality rate (HR 1.10 [95% CI: 1.00, 1.21] among women and 1.02 [95% CI: 0.93, 1.11] among men). For all patient groups as well as for the general population, the three leading causes of death were cardiovascular diseases, neoplasms and respiratory diseases. RA patients had increased mortality from all of these causes, while axSpA patients had increased mortality from cardiovascular and respiratory diseases. CONCLUSION: Even in the era of modern treatments for IJDs, patients with RA and axSpA still have shortened life expectancy. Our findings warrant further attention to the prevention and management of comorbidities.

Preclinical cardiac organ damage during statin treatment in patients with inflammatory joint diseases: the RORA-AS statin intervention study.

OBJECTIVE: Statin treatment has been associated with reduction in blood pressure and arterial stiffness in patients with inflammatory joint diseases (IJD). We tested whether statin treatment also was associated with regression of preclinical cardiac organ damage in IJD patients. METHODS: Echocardiography was performed in 84 IJD patients (52 RA, 20 ankylosing spondylitis, 12 psoriatric arthritis, mean age 61 (9) years, 63% women) without known cardiovascular disease before and after 18 months of rosuvastatin treatment. Preclinical cardiac organ damage was identified by echocardiography as presence of left ventricular (LV) hypertrophy, LV concentric geometry, increased LV chamber size and/or dilated left atrium. RESULTS: At baseline, hypertension was present in 63%, and 36% used biologic DMARDs (bDMARDs). Preclinical cardiac organ damage was not influenced by rosuvastatin treatment (44% at baseline vs 50% at follow-up, P = 0.42). In uni- and multivariable logistic regression analyses, risk of preclinical cardiac organ damage at follow-up was increased by higher baseline body mass index [odds ratio (OR) 1.3, 95% CI: 1.1, 1.5, P = 0.01] and presence of preclinical cardiac organ damage at baseline (OR 6.4, 95% CI: 2.2, 18.5, P = 0.001) and reduced by use of bDMARDs at follow-up (OR 0.3, 95% CI: 0.1, 0.9, P = 0.03). CONCLUSION: Rosuvastatin treatment was not associated with a reduction in preclinical cardiac organ damage in IJD patients after 18 months of treatment. However, use of bDMARDS at follow-up was associated with lower risk of preclinical cardiac organ damage at study end, pointing to a possible protective cardiac effect of bDMARDs in IJD patients. CLINICALTRIALS.GOV: https://clinicaltrials.gov/NCT01389388.

Smoking cessation is associated with lower disease activity and predicts cardiovascular risk reduction in rheumatoid arthritis patients.

OBJECTIVES: Smoking is a major risk factor for the development of both cardiovascular disease (CVD) and RA and may cause attenuated responses to anti-rheumatic treatments. Our aim was to compare disease activity, CVD risk factors and CVD event rates across smoking status in RA patients. METHODS: Disease characteristics, CVD risk factors and relevant medications were recorded in RA patients without prior CVD from 10 countries (Norway, UK, Netherlands, USA, Sweden, Greece, South Africa, Spain, Canada and Mexico). Information on CVD events was collected. Adjusted analysis of variance, logistic regression and Cox models were applied to compare RA disease activity (DAS28), CVD risk factors and event rates across categories of smoking status. RESULTS: Of the 3311 RA patients (1012 former, 887 current and 1412 never smokers), 235 experienced CVD events during a median follow-up of 3.5 years (interquartile range 2.5-6.1). At enrolment, current smokers were more likely to have moderate or high disease activity compared with former and never smokers (P < 0.001 for both). There was a gradient of worsening CVD risk factor profiles (lipoproteins and blood pressure) from never to former to current smokers. Furthermore, former and never smokers had significantly lower CVD event rates compared with current smokers [hazard ratio 0.70 (95% CI 0.51, 0.95), P = 0.02 and 0.48 (0.34, 0.69), P < 0.001, respectively]. The CVD event rates for former and never smokers were comparable. CONCLUSION: Smoking cessation in patients with RA was associated with lower disease activity and improved lipid profiles and was a predictor of reduced rates of CVD events.

Strategies for implementation of guideline recommended cardiovascular risk management for patients with rheumatoid arthritis: results from a questionnaire survey of expert rheumatology centers.

The aim was to study the different strategies used to implement cardiovascular risk evaluation and management for patients with rheumatoid arthritis (RA) in daily clinical practice. A questionnaire survey was performed among both the members of the international Trans-Atlantic Cardiovascular Risk Consortium for Rheumatoid Arthritis (ATACC-RA) as well as the Survey of cardiovascular disease risk factors (CVD-RF) in patients with RA (SURF-RA) group. The questionnaire included 18 questions with the overarching topics: (1) organization and responsibility of cardiovascular risk management (CVRM); (2) screening of CVD-RFs; (3) overview current CVRM status; and (4) availability of data regarding CVRM. Based on the answers, two researchers (JW, PR) independently categorized the different strategies. Thirteen out of 27 rheumatology centers responded to the questionnaire. One rheumatology center did not have organized CVRM for their RA patients. Among the other centers, three strategies to organize CVRM in daily practice were distinguished: (1) the rheumatologist performs CVRM during outpatient visits (n = 6); (2) cardiologists and rheumatologists co-operate in a cardio-rheuma-clinic/team with different tasks and responsibilities (n = 3); and (3) the general practitioner screens and intervenes on CVD-RFs (n = 3). Each CVRM strategy was based on agreements between medical professionals and was also dependent on the national healthcare system and available financial resources. Three strategies were identified for CVRM implementation in daily clinical practice based on who is primarily responsible for performing CVRM. More research is warranted to compare their relative merits and effectiveness in relation to CVRM.

High intensity exercise for 3 months reduces disease activity in axial spondyloarthritis (axSpA): a multicentre randomised trial of 100 patients.

BACKGROUND: Exercise is considered important in the management of patients with rheumatic diseases, but the effect of high intensity exercises on disease activity is unknown. OBJECTIVE: To investigate the effectiveness of high intensity exercises on disease activity in patients with axial spondyloarthritis (axSpA). METHOD: Assessor blinded multicentre randomised controlled trial. 100 patients (aged from their 20s to their 60s) with axSpA were randomly assigned to an exercise group or to a no-intervention control group. The exercise group performed cardiorespiratory and muscular strength exercises at high intensity over 3 months. The control group received standard care and was instructed to maintain their usual physical activity level. Primary outcome was disease activity measured with the Ankylosing Spondylitis (AS) Disease Activity Scale (ASDAS, higher score=worst) and the Bath AS Disease Activity Index (BASDAI, 0-10, 10=worst). Secondary outcomes were inflammatory markers, physical function and cardiovascular (CV)-health. There was patient involvement in the design and reporting of this study. RESULTS: 97 of the 100 (97%) randomised patients completed the measurements after the intervention. There was a significant treatment effect of the intervention on the primary outcome (ASDAS: -0.6 [-0.8 to -0.3], p<0.001 and BASDAI: -1.2 [-1.8 to -0.7], p<0.001). Significant treatment effects were also seen for inflammation, physical function and CV-health. CONCLUSION: High intensity exercises reduced disease symptoms (pain, fatigue, stiffness) and also inflammation in patients with axSpA. It improves patients' function and CV health. This debunks concerns that high intensity exercise might exacerbate disease activity in patients with axSpA. TRIAL REGISTRATION NUMBER: NCT02356874.

Smoking cessation intervention for reducing disease activity in chronic autoimmune inflammatory joint diseases.

BACKGROUND: Chronic inflammatory joint diseases (IJDs) affect 1% to 2% of the population in developed countries. IJDs include rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), and other forms of spondyloarthritis (SpA). Tobacco smoking is considered a significant environmental risk factor for developing IJDs. There are indications that smoking exacerbates the symptoms and worsens disease outcomes. OBJECTIVES: The objective of this review was to investigate the evidence for effects of smoking cessation interventions on smoking cessation and disease activity in smokers with IJD. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Library; PubMed/MEDLINE; Embase; PsycINFO; the Cumulative Index to Nursing and Allied Health Literature (CINAHL); and three trials registers to October 2018. SELECTION CRITERIA: We included randomised controlled trials testing any form of smoking cessation intervention for adult daily smokers with a diagnosis of IJD, and measuring smoking cessation at least six months after baseline. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as expected by Cochrane. MAIN RESULTS: We included two studies with 57 smokers with a diagnosis of rheumatoid arthritis (RA). We identified no studies including other IJDs. One pilot study compared a smoking cessation intervention specifically for people with RA with a less intensive, generic smoking cessation intervention. People included in the study had a mean age of 56.5 years and a disease duration of 7.7 years (mean). The second study tested effects of an eight-week cognitive-behavioural patient education intervention on cardiovascular disease (CVD) risk for people with RA and compared this with information on CVD risk only. The intervention encouraged participants to address multiple behaviours impacting CVD risk, including smoking cessation, but did not target smoking cessation alone. People included in the study had a mean age of 62.2 years (intervention group) and 60.8 years (control group), and disease duration of 11.6 years (intervention group) and 14.1 years (control group). It was not appropriate to perform a meta-analysis of abstinence data from the two studies due to clinical heterogeneity between interventions. Neither of the studies individually provided evidence to show benefit of the interventions tested. Only one study reported on adverse effects. These effects were non-serious, and numbers were comparable between trial arms. Neither of the studies assessed or reported disease activity or any of the predefined secondary outcomes. We assessed the overall certainty of evidence as very low due to indirectness, imprecision, and high risk of detection bias based on GRADE. AUTHORS' CONCLUSIONS: We found very little research investigating the efficacy of smoking cessation intervention specifically in people with IJD. Included studies are limited by imprecision, risk of bias, and indirectness. Neither of the included studies investigated whether smoking cessation intervention reduced disease activity among people with IJD. High-quality, adequately powered studies are warranted. In particular, researchers should ensure that they measure disease markers and quality of life, in addition to long-term smoking cessation.

Impact of risk factors associated with cardiovascular outcomes in patients with rheumatoid arthritis.

OBJECTIVES: Patients with rheumatoid arthritis (RA) have an excess risk of cardiovascular disease (CVD). We aimed to assess the impact of CVD risk factors, including potential sex differences, and RA-specific variables on CVD outcome in a large, international cohort of patients with RA. METHODS: In 13 rheumatology centres, data on CVD risk factors and RA characteristics were collected at baseline. CVD outcomes (myocardial infarction, angina, revascularisation, stroke, peripheral vascular disease and CVD death) were collected using standardised definitions. RESULTS: 5638 patients with RA and no prior CVD were included (mean age: 55.3 (SD: 14.0) years, 76% women). During mean follow-up of 5.8 (SD: 4.4) years, 148 men and 241 women developed a CVD event (10-year cumulative incidence 20.9% and 11.1%, respectively). Men had a higher burden of CVD risk factors, including increased blood pressure, higher total cholesterol and smoking prevalence than women (all p<0.001). Among the traditional CVD risk factors, smoking and hypertension had the highest population attributable risk (PAR) overall and among both sexes, followed by total cholesterol. The PAR for Disease Activity Score and for seropositivity were comparable in magnitude to the PAR for lipids. A total of 70% of CVD events were attributable to all CVD risk factors and RA characteristics combined (separately 49% CVD risk factors and 30% RA characteristics). CONCLUSIONS: In a large, international cohort of patients with RA, 30% of CVD events were attributable to RA characteristics. This finding indicates that RA characteristics play an important role in efforts to reduce CVD risk among patients with RA.

On the HUNT for cardiovascular risk factors and disease in patients with psoriatic arthritis: population-based data from the Nord-Trøndelag Health Study.

OBJECTIVE: To compare the presence of cardiovascular (CV) risk factors and established CV disease in patients with psoriatic arthritis (PsA) and the general population and to compare the 10-year risk of a fatal CV event calculated by the Systematic Coronary Risk Evaluation (SCORE) algorithm. METHODS: Patients with PsA (n=338) and controls (n=50 468) were recruited from the Nord-Trøndelag Health Study 3. Age-adjusted and sex-adjusted prevalence rates of CV risk factors and comorbidity were calculated and the SCORE algorithm was applied. RESULTS: There was an increased prevalence of angina pectoris (5.0% vs 3.6%, p=0.01), history of percutaneous coronary intervention (2.4% vs 1.4%, p=0.04), hypertension (45.3% vs 39.3%, p=0.01), obesity (32.0% vs 22.4%) and tobacco smoking (21.3% vs 16.4%, p=0.02) in patients with PsA compared with controls. Patients with PsA had elevated levels of C reactive protein (CRP; p<0.001), body mass index (BMI; p<0.001) and triglycerides (p=0.01). The median calculated CV risk in patients with PsA was low and comparable with controls (0.87 vs 0.83, p=0.24). The distribution across CV risk classes was similar among patients with PsA and controls. CONCLUSIONS: Patients with PsA have a higher risk of CV disease than the background population, although there was no difference between groups in 10-year risk of a fatal CV event estimated by SCORE. However, patients with PsA had elevated levels of CV risk factors not included in the SCORE algorithm, such as BMI, triglycerides and CRP.

The association of hypertension with asymptomatic cardiovascular organ damage in rheumatoid arthritis.

BACKGROUND: The association of hypertension with asymptomatic cardiovascular organ damage in patients with rheumatoid arthritis (RA) has been little studied by echocardiography. METHODS: Echocardiography was done in 134 RA patients and 102 healthy controls. Left ventricular (LV) geometry was considered abnormal if LV mass index or relative wall thickness was increased. LV diastolic dysfunction was considered present if septal early diastolic tissue velocity <8 cm/s. Systemic arterial compliance (SAC) was assessed from stroke volume index/pulse pressure ratio. RESULTS: The hypertensive RA patients (n = 72) had higher inflammatory activity, older age and more diabetes than the normotensive RA patients (n = 62) (all p < 0.05). Rates of abnormal LV geometry, LV diastolic dysfunction and lower SAC were higher among the hypertensive RA patients (p < 0.05), but similar between normotensive RA patients and controls. Hypertension was associated with a 3-fold higher prevalence both for abnormal LV geometry (odds ratio 2.89 [95% confidence interval 1.09-7.63], p = 0.03) and for diastolic LV dysfunction (odds ratio 2.92 [95% confidence interval 1.14-7.46], p = 0.03) as well as lower SAC (ß = 0.31, p = 0.001) independent of age, gender, diabetes and inflammatory activity measured by erythrocyte sedimentation rate. CONCLUSION: The presence of asymptomatic cardiovascular organ damage in RA patients is closely associated with hypertension independent of inflammatory activity.

Cardiovascular disease assessment in rheumatoid arthritis: a guide to translating knowledge of cardiovascular risk into clinical practice.

As physicians we like to have evidence for making decisions about interventions to improve health. The evidence vacuum in the field of cardiovascular disease (CVD) prevention and clinical outcome in patients with rheumatoid arthritis (RA) has received vigorous attention in the recent literature. There is broad agreement that a patient with RA fulfilling the criteria established for the general population on CVD risk reduction should receive proven interventions, including smoking cessation, weight reduction, blood pressure control and lipid-lowering therapy. In accordance with these recommendations, and despite all the uncertainties about CVD treatment threshold, targets and outcome results in RA, we firmly advocate that CVD risk should be assessed and acted on in patients with RA as recommended for the general population, even while educational CVD-preventive programmes are being developed and hard CVD end point studies are undertaken in this patient population. The initial strategies for implementing CVD risk evaluation will necessarily be modest at first. There are several possible strategies for collection of data that can be incorporated into the daily routine during rheumatology consultations at outpatient clinics. We recommend starting with these simple procedures: 1. CVD risk factor recording and evaluation using risk calculators available for the general population 2. Referral of patients with high CVD risk to a primary care physician or a cardiologist skilled in this subject for follow-up 3. Providing information about excess CVD risk and how to modify it to the patients as major stakeholders.

Non-steroidal anti-inflammatory drugs and risk of pulmonary embolism in patients with inflammatory joint disease-results from the nationwide Norwegian Cardio-rheuma registry.

AIMS: Patients with inflammatory joint diseases (IJD), including rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) have increased rates of pulmonary embolism (PE). Non-steroidal anti-inflammatory drugs (NSAIDs) use is associated with PE in the general population. Our aim was to evaluate the association between NSAIDs use and PE in IJD patients. METHODS AND RESULTS: Using individual-level registry data from the whole Norwegian population, including data from the Norwegian Patient Registry and the Norwegian Prescription Database, we: (1) evaluated PE risk in IJD compared to non-IJD individuals, (2) applied the self-controlled case series method to evaluate if PE risks were associated with use of traditional NSAIDs (tNSAIDs) and selective cox-2 inhibitors (coxibs). After a one-year wash-out period, we followed 4 660 475 adults, including 74 001 with IJD (RA: 39 050, PsA: 20 803, and axSpA: 18 591) for a median of 9.0 years. Crude PE incidence rates per 1000 patient years were 2.02 in IJD and 1.01 in non-IJD individuals. Age and sex adjusted hazard ratios for PE events were 1.57 for IJD patients compared to non-IJD. Incidence rate ratios (IRR) [95% confidence interval (CI)] for PE during tNSAIDs use were 0.78 (0.64-0.94, P = 0.010) in IJD and 1.68 (1.61-1.76, P < 0.001) in non-IJD. IRR (95% CI) for PE during coxibs use was 1.75 (1.10-2.79, P = 0.018) in IJD and 2.80 (2.47-3.18, P < 0.001) for non-IJD. CONCLUSION: Pulmonary embolism rates appeared to be higher in IJD than among non-IJD subjects in our study. Traditional NSAIDs may protect against PE in IJD patients, while coxibs may associated with increased PE risk.

Treatment to lipid targets in patients with inflammatory joint diseases in a preventive cardio-rheuma clinic.

OBJECTIVES: To perform cardiovascular risk stratification in patients with inflammatory joint diseases (IJD) and treat to lipid targets according to recommendations. METHODS: We initiated a preventive cardio-rheuma clinic based on the unmet need of adequate cardiovascular prevention in IJD patients. A full cardiovascular risk stratification was performed at the first consultation (history of conventional risk factors and of cardiovascular disease, lipid measurement, blood pressure and ultrasound examination of both carotid arteries), and the patient was classified to either a primary or secondary cardiovascular prevention regime, or to have a low risk (no intervention). Lipid-lowering treatment was adjusted until at least two lipid targets were achieved. RESULTS: Of the 426 patients referred, 36.6% had a systematic coronary risk evaluation less than 5% (no lipid-lowering intervention). The remaining 270 patients ((rheumatoid arthritis (RA), n=165; ankylosing spondylitis (AS), n=70; and psoriatic arthritis (PsA), n=35) were assigned to either primary (n=63) or secondary prevention (n=207). There were significant differences between the patient groups regarding age (p<0.001), sex (p<0.001) and disease duration (p<0.001). Lipid changes in IJD patients were: total cholesterol -1.86±1.20 mmol/l (p<0.001); low-density lipoprotein cholesterol -1.74±1.11 (p<0.001); high-density lipoprotein cholesterol 0.01±0.30 (p=0.61); triglycerides -0.28±0.72 (p<0.001). The proportions of patients reaching at least two lipid targets were for RA 92.1%, AS 90.0% and PsA 82.9%. No serious adverse events were observed. CONCLUSIONS: There was indication for cardiovascular prevention in a high proportion of IJD patients referred for cardiovascular risk stratification. Treatment to lipid targets was successful in approximately 90% of patients with IJD.

Hand, hip and knee osteoarthritis in a Norwegian population-based study--the MUST protocol.

BACKGROUND: Knowledge about the prevalence and consequences of osteoarthritis (OA) in the Norwegian population is limited. This study has been designed to gain a greater understanding of musculoskeletal pain in the general population with a focus on clinically and radiologically confirmed OA, as well as risk factors, consequences, and management of OA. METHODS/DESIGN: The Musculoskeletal pain in Ullensaker STudy (MUST) has been designed as an observational study comprising a population-based postal survey and a comprehensive clinical examination of a sub-sample with self-reported OA (MUST OA cohort). All inhabitants in Ullensaker municipality, Norway, aged 40 to 79 years receive the initial population-based postal survey questionnaire with questions about life style, general health, musculoskeletal pain, self-reported OA, comorbidities, health care utilisation, medication use, and functional ability. Participants who self-report OA in their hip, knee and/or hand joints are asked to attend a comprehensive clinical examination at Diakonhjemmet Hospital, Oslo, including a comprehensive medical examination, performance-based functional tests, different imaging modalities, cardiovascular assessment, blood and urine samples, and a number of patient-reported questionnaires including five OA disease specific instruments. Data will be merged with six national data registries. A subsample of those who receive the questionnaire has previously participated in postal surveys conducted in 1990, 1994, and 2004 with data on musculoskeletal pain and functional ability in addition to demographic characteristics and a number of health related factors. This subsample constitutes a population based cohort with 20 years follow-up. DISCUSSION: This protocol describes the design of an observational population-based study that will involve the collection of data from a postal survey on musculoskeletal pain, and a comprehensive clinical examination on those with self-reported hand, hip and/or knee OA. These data, in addition to data from national registries, will provide unique insights into clinically and radiologically confirmed OA with respect to risk factors, consequences, and management.

Urate crystal deposition is associated with inflammatory markers and carotid artery pathology in patients with intercritical gout: results from the NOR-Gout study.

BACKGROUND: Gout is of unknown reason associated with cardiovascular disease. Ultrasound is sensitive for detecting crystal deposition and plasma calprotectin is a sensitive inflammatory marker. This study explores the associations between crystal deposition, inflammation and carotid artery pathology. METHOD: A cross-sectional analysis of baseline assessments from the NOR-Gout study was undertaken. Crystal deposition was assessed by ultrasound (double contour, tophi, aggregates) and dual-energy CT (DECT) and laboratory assessments included plasma calprotectin. The carotid arteries were bilaterally examined for carotid intima-media thickness (cIMT) and presence of plaques. Spearman correlations, Mann-Whitney tests and linear regression analyses were used to explore associations between crystal deposition, inflammatory markers,and carotid pathology. RESULTS: 202 patients with intercritical gout (95.5% men, mean (SD) age 56.5 (13.8) years, disease duration 7.9 (7.7) years) were included. Calprotectin was correlated with all scores of crystal deposition by ultrasound (r=0.26-0.32, p<0.001) and DECT (r=0.15, p<0.05). cIMT was correlated with sum score aggregates (r=0.18-0.22, p<0.05). Patients with large tophi had higher levels of calprotectin as well as more frequent carotid plaque (p<0.05). CONCLUSIONS: Study findings point towards crystal deposition contributing to subclinical inflammation with subsequent vascular implications. However, future longitudinal studies are needed to confirm such causal relationships.

Oral anticoagulant treatment in rheumatoid arthritis patients with atrial fibrillation results of an international audit.

Objective: To describe the prevalence of atrial fibrillation (AF) in patients with rheumatoid arthritis (RA), and to evaluate the proportion of patients with AF receiving guideline-recommended anticoagulation for prevention of stroke, based on data from a large international audit. Methods: The cohort was derived from the international audit SUrvey of cardiovascular disease Risk Factors in patients with Rheumatoid Arthritis (SURF-RA) which collected data from 17 countries during 2014-2019. We evaluated the prevalence of AF across world regions and explored factors associated with the presence of AF with multivariable logistic regression models. The proportion of AF patients at high risk of stroke (CHA2DS2-VASc ≥ 2 in males and ≥ 3 in females) receiving anticoagulation was examined. Results: Of the total SURF-RA cohort (n = 14,503), we included RA cases with data on whether the diagnosis of AF was present or not (n = 7,665, 75.1% women, mean (SD) age 58.7 (14.1) years). A total of 288 (3.8%) patients had a history of AF (4.4% in North America, 3.4% in Western Europe, 2.8% in Central and Eastern Europe and 1.5% in Asia). Factors associated with the presence of AF were older age, male sex, atherosclerotic cardiovascular disease, heart failure and hypertension. Two-hundred and fifty-five (88.5%) RA patients had a CHA2DS2-VASc score indicating recommendation for oral anticoagulant treatment, and of them, 164 (64.3%) were anticoagulated. Conclusion: Guideline-recommended anticoagulant therapy for prevention of stroke due to AF may not be optimally implemented among RA patients, and requires special attention.

A Clinical Audit of Cardiovascular Risk Factors and Disease in Patients with Rheumatoid Arthritis - SURF-RA.

Background and aims: Rheumatoid arthritis (RA) patients are at a high risk of atherosclerotic cardiovascular disease (ASCVD). This implies a need for meticulous CVD risk factor recording and control. Objectives: The aim was to evaluate the international prevalence of ASCVD in RA patients and to audit the prevalence and control of CVD risk factors. Methods: A SUrvey of cardiovascular disease Risk Factors in patients with Rheumatoid Arthritis (SURF-RA) was performed at 53 centres in 19 countries in three continents between 2014 and 2019. CVD risk factors, medication, and physical and laboratory measurements were recorded. CVD risk was estimated using the ESC's SCORE system. Results: Among 14503 RA patients in Western (n=8493) and Central and Eastern (n=923) Europe, Mexico (n=407), North America (n=4030) and Asia (n=650) (mean age 59.9 years, 74.5% female), ASCVD was present in 15%, varying from 2.5% in Mexico to 21% in Central and Eastern Europe. Sixty-two percent reported hypertension and 63% had a LDL-c of > 2.5 mmol/L. Mean BMI was 27.4 kg/m2 in the total cohort, highest in North America (29.7 kg/m2), and lowest in Asia (23.8 kg/m2). A sixth of patients were current smokers, and 13% had diabetes mellitus. Approximately 45% had an estimated high or very high risk of fatal CVD according to SCORE algorithm, and ¾ of patients had only ≤4/6 CVD risk factors at recommended target. Conclusion: Among RA patients across three continents, established CVD and CVD risk factors are common, although geographical variation exists. Furthermore, CVD risk factors often remain inadequately controlled.

An international audit of the management of dyslipidaemia and hypertension in patients with rheumatoid arthritis: results from 19 countries.

AIMS: To assess differences in estimated cardiovascular disease (CVD) risk among rheumatoid arthritis (RA) patients from different world regions and to evaluate the management and goal attainment of lipids and blood pressure (BP). METHODS AND RESULTS: The survey of CVD risk factors in patients with RA was conducted in 14 503 patients from 19 countries during 2014-19. The treatment goal for BP was <140/90 mmHg. CVD risk prediction and lipid goals were according to the 2016 European guidelines. Overall, 21% had a very high estimated risk of CVD, ranging from 5% in Mexico, 15% in Asia, 19% in Northern Europe, to 31% in Central and Eastern Europe and 30% in North America. Of the 52% with indication for lipid-lowering treatment (LLT), 44% were using LLT. The lipid goal attainment was 45% and 18% in the high and very high risk groups, respectively. Use of statins in monotherapy was 24%, while 1% used statins in combination with other LLT. Sixty-two per cent had hypertension and approximately half of these patients were at BP goal. The majority of the patients used antihypertensive treatment in monotherapy (24%), while 10% and 5% as a two- or three-drug combination. CONCLUSION: We revealed considerable geographical differences in estimated CVD risk and preventive treatment. Low goal attainment for LLT was observed, and only half the patients obtained BP goal. Despite a high focus on the increased CVD risk in RA patients over the last decade, there is still substantial potential for improvement in CVD preventive measures.

Atherosclerotic Cardiovascular Disease in Rheumatoid Arthritis: Impact of Inflammation and Antirheumatic Treatment.

Patients with rheumatoid arthritis (RA) are at approximately 1.5-fold risk of atherosclerotic cardiovascular disease (CVD) compared with the general population, a phenomenon resulting from combined effects of traditional CVD risk factors and systemic inflammation. Rheumatoid synovitis and unstable atherosclerotic plaques share common inflammatory mechanisms, such as expression of proinflammatory cytokines interleukin (IL)-1, tumour necrosis factor (TNF)-α and IL-6. RA patients are undertreated in terms of CVD prevention, and structured CVD prevention programmes are warranted. Alongside management of traditional risk factors, suppressing systemic inflammation with antirheumatic medication is fundamental for the reduction of CVD risk among this high-risk patient group. Many antirheumatic drugs, especially methotrexate, TNF-α-inhibitors and IL-6-inhibitors are associated with reduced risk of CVD in observational studies among RA patients, but randomised controlled trials with hard CVD endpoints are lacking. In patients without rheumatic disease, anti-inflammatory therapies targeting nucleotide-binding oligomerisation domain, leucine-rich repeat and pyrin domain-containing protein 3 inflammasome and the IL-1/IL-6 pathway arise as potential therapies after an atherosclerotic CVD event.