Review: The Role of Dual-Energy Computed Tomography in Detecting Monosodium Urate Deposits in Vascular Tissues.

PURPOSE OF REVIEW: To highlight novel findings in the detection of monosodium urate deposits in vessels using dual energy computed tomography, and to discuss the potential clinical implications for gout and hyperuricemia patients. RECENT FINDINGS: Gout is an independent risk factor for cardiovascular disease. However, classical risk calculators do not take into account these hazards, and parameters to identify patients at risk are lacking. Monosodium urate measured by dual energy computed tomography is a well-established technology for the detection and quantification of monosodium urate deposits in peripheral joints and tendons. Recent findings also suggest its applicability to identify vascular urate deposits. Dual energy computed tomography is a promising tool for detection of cardiovascular monosodium urate deposits in gout patients, to better delineate individuals at increased risk for cardiovascular disease.

Major cardiovascular events in patients with cardiovascular monosodium urate deposits in atherosclerotic plaques.

OBJECTIVE: To determine the association of cardiovascular atherosclerotic plaque monosodium urate deposits with the occurrence of major cardiovascular events in gout and hyperuricemia patients. METHODS: This retrospective cohort study included patients with clinically suspicion of gout, who performed a dual energy computed tomography of the affected limb and thorax between June 1st, 2012 and December 5th, 2019. Clinical and laboratory parameters were retrieved from patients charts. Established cardiovascular risk factors were evaluated. Medical history review identified the presence of major adverse cardiac events with a median follow up time of 33 months (range 0-108 months) after the performed computed tomography scan. RESULTS: Full data sets were available for 189 patients: 131 (69.3%) gout patients, 40 (21.2%) hyperuricemia patients, and 18 (9.5%) controls. Patients with cardiovascular monosodium urate deposits (n = 85/189, 45%) revealed increased serum acute phase reactants, uric acid levels and calcium scores in computed tomography compared with patients without cardiovascular monosodium urate deposits. Major adverse cardiac events were observed in 35 patients (18.5%) with a higher prevalence in those patients revealing cardiovascular monosodium urate deposits (n = 22/85, 25.9%) compared with those without cardiovascular monosodium urate deposits (n = 13/104, 12.5%, OR 2.4, p= 0.018). CONCLUSION: This is the first study demonstrating the higher hazard of major adverse cardiac events in patients with dual energy computed tomography-verified cardiovascular monosodium urate deposits. The higher prevalence of cardiac events in patients with cardiovascular monosodium urate deposits may facilitate risk stratification of gout patients, as classical cardiovascular risk scores or laboratory markers fail in their proper identification.

Coalition for Health and Gender Equity (CHANGE)-a protocol for a global cross-sectional survey of health and gender equity in rheumatology.

Objectives: The primary aim of the CHANGE survey is to determine the current state of gender equity within rheumatology, and secondarily, to review the physician perspective on bullying, harassment and equipoise of opportunities within rheumatology. Methods: The CHANGE e-survey is a cross-sectional self-reported questionnaire adapted from EULAR's gender equity in academic rheumatology task force. The survey was launched in January 2023; it is available in six languages and distributed widely via rheumatology organizations and social media. Eligible participants include rheumatologist physicians and rheumatology health-care professionals. Survey responses will undergo descriptive analysis and inter-group comparison aiming to explore gender-based discrimination using logistic regression, with subgroup analyses for country/continent variations. Conclusion: This e-survey represents a comprehensive global initiative led by an international consortium, aimed at exploring and investigating the gender-related disparities and obstacles encountered by rheumatologists and rheumatology health-care professionals across diverse communities and health-care environments. By pursuing this initiative, we aim to take the broader rheumatology community a step closer to understanding the underlying origins of inequities and their determinants. Such insights are pivotal in identifying viable interventions and strategies to foster gender equity within the field. Ultimately, our collective objective is to ensure equitable access to opportunities for every individual, irrespective of gender, thereby promoting inclusivity and fairness across the entire spectrum of professional practice and career development.

Treat-to-target recommendations in giant cell arteritis and polymyalgia rheumatica.

OBJECTIVES: To develop treat-to-target (T2T) recommendations in giant cell arteritis (GCA) and polymyalgia rheumatica (PMR). METHODS: A systematic literature review was conducted to retrieve data on treatment targets and outcomes in GCA/PMR as well as to identify the evidence for the effectiveness of a T2T-based management approach in these diseases. Based on evidence and expert opinion, the task force (29 participants from 10 countries consisting of physicians, a healthcare professional and a patient) developed recommendations, with consensus obtained through voting. The final level of agreement was provided anonymously. RESULTS: Five overarching principles and six-specific recommendations were formulated. Management of GCA and PMR should be based on shared decisions between patient and physician recognising the need for urgent treatment of GCA to avoid ischaemic complications, and it should aim at maximising health-related quality of life in both diseases. The treatment targets are achievement and maintenance of remission, as well as prevention of tissue ischaemia and vascular damage. Comorbidities need to be considered when assessing disease activity and selecting treatment. CONCLUSION: These are the first T2T recommendations for GCA and PMR. Treatment targets, as well as strategies to assess, achieve and maintain these targets have been defined. The research agenda highlights the gaps in evidence and the need for future research.

[Diagnosis and therapy of granulomatosis with polyangiitis and microscopic polyangiitis-2023: consensus of the Austrian society of nephrology (ÖGN) and Austrian society of rheumatology (ÖGR)]. / Diagnose und Therapie der Granulomatose mit Polyangiitis und mikroskopische Polyangiitis ­ 2023: Konsens-Empfehlungen der Österreichischen Gesellschaften für Nephrologie (ÖGN) & Rheumatologie (ÖGR).

ANCA-associated vasculitides (AAV) are rare, complex systemic diseases that are often difficult to diagnose, because of unspecific clinical symptoms at presentation. However, the clinical course may be very dramatic and even life-threatening, necessitating prompt diagnosis and treatment.Therefore, it is important to increase disease awareness among physicians and support colleagues who are not confronted with these rare diseases on a regular basis. Here, the Austrian Society of Nephrology (ÖGN) and the Austrian Society of Rheumatology (ÖGR) provide a joint consensus on how to best diagnose and manage patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA).

EULAR recommendations for the use of imaging in large vessel vasculitis in clinical practice: 2023 update.

OBJECTIVES: To update the EULAR recommendations for the use of imaging modalities in primary large vessel vasculitis (LVV). METHODS: A systematic literature review update was performed to retrieve new evidence on ultrasound, MRI, CT and [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) for diagnosis, monitoring and outcome prediction in LVV. The task force consisted of 24 physicians, health professionals and patients from 14 countries. The recommendations were updated based on evidence and expert opinion, iterating until voting indicated consensus. The level of agreement was determined by anonymous votes. RESULTS: Three overarching principles and eight recommendations were agreed. Compared to the 2018 version, ultrasound is now recommended as first-line imaging test in all patients with suspected giant cell arteritis, and axillary arteries should be included in the standard examination. As an alternative to ultrasound, cranial and extracranial arteries can be examined by FDG-PET or MRI. For Takayasu arteritis, MRI is the preferred imaging modality; FDG-PET, CT or ultrasound are alternatives. Although imaging is not routinely recommended for follow-up, ultrasound, FDG-PET or MRI may be used for assessing vessel abnormalities in LVV patients with suspected relapse, particularly when laboratory markers of inflammation are unreliable. MR-angiography, CT-angiography or ultrasound may be used for long-term monitoring of structural damage, particularly at sites of preceding vascular inflammation. CONCLUSIONS: The 2023 EULAR recommendations provide up-to-date guidance for the role of imaging in the diagnosis and assessment of patients with LVV.

Tissue iron distribution in patients with anemia of inflammation: Results of a pilot study.

Anemia of inflammation (AI) is frequently present in subjects with inflammatory disorders, primarily caused by inflammation-driven iron retention in macrophages. So far, only limited data on qualitative and quantitative estimates of tissue iron retention in AI patients exist. We performed a prospective cohort study analyzing splenic, hepatic, pancreatic, and cardiac iron content with MRI-based R2*-relaxometry in AI patients, including subjects with concomitant true iron deficiency (AI+IDA) hospitalized between 05/2020-01/2022. Control groups were individuals without inflammation. Spleen R2* values in AI patients with ferritin ≤200 µg/L (AI+IDA) were comparable with those found in controls. In AI patients with ferritin >200 µg/L, spleen (47.6 s-1 vs. 19.3 s-1 , p < .001) and pancreatic R2* values (32.5 s-1 vs. 24.9 s-1 , p = .011) were significantly higher compared with controls, while liver and heart R2*-values did not differ. Higher spleen R2* values were associated with higher ferritin, hepcidin, CRP, and IL-6 concentrations. Spleen R2* values normalized in AI patients after recovery (23.6 s-1 vs. 47.6 s-1 , p = .008), while no changes were found in patients with baseline AI+IDA. This is the first study investigating tissue iron distribution in patients with inflammatory anemia and AI with concomitant true iron deficiency. The results support the findings in animal models demonstrating iron retention in macrophages, which are primarily accumulating in the spleen under inflammatory conditions. MRI-related iron measurement may help to better characterize actual iron needs and to define better biomarker thresholds in the diagnosis of true ID in patients with AI. It may qualify as a useful diagnostic method to estimate the need for iron supplementation and to guide therapy.

How to plug the leaky pipeline in clinical rheumatology across Europe-lessons to be learned from experiences in business.

OBJECTIVES: While >50% of medical students and residents are women, their proportion drastically diminishes within higher ranks and leadership roles; this is known as the 'leaky pipeline'. We aimed to evaluate the leaky pipeline among rheumatologists across Europe and to assess determinants inducing rheumatologists to leave hospitals. METHODS: Experts in the field of economics developed a questionnaire with scientific focus on the leaky pipeline among rheumatologists, which was distributed electronically by national scientific societies of EULAR countries and by individual contacts. We performed common factor analysis, univariate t-tests and multivariate regression analyses to appraise our dataset. RESULTS: A total of 311 hospital-based rheumatologists from 23/45 EULAR countries (52.7% females, 47.3% males) answered the questionnaire. The presence of the leaky pipeline was evident for the entire sample. Of 64% female rheumatologists only 34.2% of departments' directors were female, with noteworthy regional differences. Female doctors reported higher intentions to leave their hospital (ß = 0.28, P < 0.05) and lower commitment towards their current organization (ß = -0.34, P < 0.05) when compared with males. Women reported lower levels of job satisfaction (ß = -0.26, P < 0.10), promotion justice (ß = -0.55, P < 0.01) and career perspectives (ß = -0.26, P < 0.10, one-tailed) than men, explaining their lower organizational commitment. CONCLUSION: Female rheumatologists perceive worse job opportunities and satisfaction than males. Many reasons for the leaky pipeline are beyond the control of organizations. Based on our results, organizations should be encouraged to reconsider and adjust their performance management practices to enable an equitable work environment.

The provisional OMERACT ultrasonography score for giant cell arteritis.

OBJECTIVES: To develop an Outcome Measures in Rheumatology (OMERACT) ultrasonography score for monitoring disease activity in giant cell arteritis (GCA) and evaluate its metric properties. METHODS: The OMERACT Instrument Selection Algorithm was followed. Forty-nine members of the OMERACT ultrasonography large vessel vasculitis working group were invited to seven Delphi rounds. An online reliability exercise was conducted using images of bilateral common temporal arteries, parietal and frontal branches as well as axillary arteries from 16 patients with GCA and 7 controls. Sensitivity to change and convergent construct validity were tested using data from a prospective cohort of patients with new GCA in which ultrasound-based intima-media thickness (IMT) measurements were conducted at weeks 1, 3, 6, 12 and 24. RESULTS: Agreement was obtained (92.7%) for the OMERACT GCA Ultrasonography Score (OGUS), calculated as follows: sum of IMT measured in every segment divided by the rounded cut-off values of IMTs in each segment. The resulting value is then divided by the number of segments available. Thirty-five members conducted the reliability exercise, the interrater intraclass correlation coefficient (ICC) for the OGUS was 0.72-0.84 and the median intrareader ICC was 0.91. The prospective cohort consisted of 52 patients. Sensitivity to change between baseline and each follow-up visit up to week 24 yielded standardised mean differences from -1.19 to -2.16, corresponding to large and very large magnitudes of change, respectively. OGUS correlated moderately with erythrocyte sedimentation rate, C reactive protein and Birmingham Vasculitis Activity Score (corrcoeff 0.37-0.48). CONCLUSION: We developed a provisional OGUS for potential use in clinical trials.

[National consensus statement by the Austrian Societies for Rheumatology, Pulmonology, Infectiology, Dermatology and Gastroenterology regarding the management of latent tuberculosis and the associated utilization of biologic and targeted synthetic DMARDS (disease modifying antirheumatic drugs)]. / Consensus Statement der Österreichischen Gesellschaften für Rheumatologie und Rehabilitation, Pneumologie, Infektiologie, Dermatologie und Gastroenterologie zum Umgang mit latenter Tuberkulose bei Therapien mit biologischen oder "targeted synthetic" DMARDs ("disease modifying antirheumatic drugs").

This nationwide Austrian consensus statement summarizes the recommendations on the management of latent tuberculosis by treatment with biologic and targeted synthetic DMARDs. The essential questions with respect to screening and preventive treatment were discussed by experts from the disciplines of rheumatology, pneumology, infectious diseases, dermatology and gastroenterology, based on the available data, and then a joint consensus was formed by agreement. This involved a differentiated discussion on the various forms of treatment, and clear recommendations were formulated.

National consensus statement by the Austrian Societies for Rheumatology, Pulmonology, Infectiology, Dermatology and Gastroenterology regarding the management of latent tuberculosis and the associated utilization of biologic and targeted synthetic disease modifying antirheumatic drugs (DMARDs).

This publication provides a thorough analysis of the most relevant topics concerning the management of latent tuberculosis when using biologic and targeted synthetic Disease Modifying Antirheumatic Drugs (DMARDs) by a multidisciplinary, select committee of Austrian physicians. The committee includes members of the Austrian Societies for Rheumatology and Rehabilitation, Pulmonology, Infectiology, Dermatology and Gastroenterology. Consensus was reached on issues regarding screening and treatment of latent tuberculosis and includes separate recommendations for each biologic and targeted synthetic DMARD.

2022 EULAR points to consider for remote care in rheumatic and musculoskeletal diseases.

BACKGROUND: Remote care and telehealth have the potential to expand healthcare access, and the COVID-19 pandemic has called for alternative solutions to conventional face-to-face follow-up and monitoring. However, guidance is needed on the integration of telehealth into clinical care of people with rheumatic and musculoskeletal diseases (RMD). OBJECTIVE: To develop EULAR points to consider (PtC) for the development, prioritisation and implementation of telehealth for people with RMD. METHODS: A multidisciplinary EULAR task force (TF) of 30 members from 14 European countries was established, and the EULAR standardised operating procedures for development of PtC were followed. A systematic literature review was conducted to support the TF in formulating the PtC. The level of agreement among the TF was established by anonymous online voting. RESULTS: Four overarching principles and nine PtC were formulated. The use of telehealth should be tailored to patient's needs and preferences. The healthcare team should have adequate equipment and training and have telecommunication skills. Telehealth can be used in screening for RMD as preassessment in the referral process, for disease monitoring and regulation of medication dosages and in some non-pharmacological interventions. People with RMD should be offered training in using telehealth, and barriers should be resolved whenever possible.The level of agreement to each statement ranged from 8.5 to 9.8/10. CONCLUSION: The PtC have identified areas where telehealth could improve quality of care and increase healthcare access. Knowing about drivers and barriers of telehealth is a prerequisite to successfully establish remote care approaches in rheumatologic clinical practice.

The role of tender and swollen joints for the assessment of inflammation in PsA using ultrasound.

OBJECTIVE: To evaluate tender joints (TJ) and swollen joints (SJ) for the assessment of ultrasound (US) defined inflammation in PsA. METHODS: Eighty-three PsA patients underwent clinical and US examinations at two scheduled study visits 12 months apart. Tenderness and swelling were assessed at 68 and 66 joints, respectively, and US examinations were conducted at all 68 joints. At patient level, associations with clinical composites and US scores were performed using correlations and by analysing patients with predominantly tender (pTender) or swollen joints (pSwollen). At joint level, a Power Doppler (PD) value ≥ 1 was defined as active synovitis. A generalized linear mixed model was created to assess the predictive value of TJ and SJ for active synovitis after 12 months. RESULTS: SJC showed better correlations with GS/PD scores (r = 0.37/0.47) than with TJC (PD: r = 0.33), while TJC correlated better with patient reported outcomes (PROMs) like patient global assessment (TJC: r = 0.57; SJC r = 0.39). Patients with pTender showed poorer results for PROMs and disease activity scores than patients with pSwollen, but not for laboratory or US markers of inflammation. Swollen joints showed active synovitis in 35% of cases, while only 16% of tender joints were active according to US. Swelling at baseline better predicted active synovitis at the same joint after 12 months [odds ratio (OR) 6.33, P <0.001] as compared with tenderness (OR 3.58, P <0.001). CONCLUSIONS: SJ are more closely linked with US signs of inflammation as compared with TJ in PsA. Joint swelling is a better predictor for signs of US inflammation than tenderness after one year of follow-up.

EULAR points to consider for the use of imaging to guide interventional procedures in patients with rheumatic and musculoskeletal diseases (RMDs).

OBJECTIVES: To develop evidence-based Points to Consider (PtC) for the use of imaging modalities to guide interventional procedures in patients with rheumatic and musculoskeletal diseases (RMDs). METHODS: European Alliance of Associations for Rheumatology (EULAR) standardised operating procedures were followed. A systematic literature review was conducted to retrieve data on the role of imaging modalities including ultrasound (US), fluoroscopy, MRI, CT and fusion imaging to guide interventional procedures. Based on evidence and expert opinion, the task force (25 participants consisting of physicians, healthcare professionals and patients from 11 countries) developed PtC, with consensus obtained through voting. The final level of agreement was provided anonymously. RESULTS: A total of three overarching principles and six specific PtC were formulated. The task force recommends preference of imaging over palpation to guide targeted interventional procedures at peripheral joints, periarticular musculoskeletal structures, nerves and the spine. While US is the favoured imaging technique for peripheral joints and nerves, the choice of the imaging method for the spine and sacroiliac joints has to be individualised according to the target, procedure, expertise, availability and radiation exposure. All imaging guided interventions should be performed by a trained specialist using appropriate operational procedures, settings and assistance by technical personnel. CONCLUSION: These are the first EULAR PtC to provide guidance on the role of imaging to guide interventional procedures in patients with RMDs.

OMERACT definition and reliability assessment of chronic ultrasound lesions of the axillary artery in giant cell arteritis.

OBJECTIVES: To define chronic ultrasound lesions of the axillary artery (AA) in long-standing giant cell arteritis (GCA) and to evaluate the reliability of the new ultrasound definition in a web-based exercise. METHODS: A structured Delphi, involving an expert panel of the Large Vessel Vasculitis subgroup of the Outcome Measures in Rheumatology (OMERACT) Ultrasound Working Group was carried out. The reliability of the new definition was tested in a 2-round web-based exercise involving 23 experts and using 50 still images each from AA of long-standing and acute GCA patients, as well as 50 images from healthy individuals. RESULTS: The final OMERACT ultrasound definition of chronic changes was based on measurement and appearance of the intima-media complex. The overall reliability of the new definition for chronic ultrasound changes in longstanding GCA of the AA was good to excellent with Light's kappa values of 0.79-0.80 for inter-reader reliability and mean Light's-kappa of 0.88 for intra-reader reliability. The mean inter-rater and intra-rater agreements were 86-87% and 92%, respectively. Good reliabilities were observed comparing the vessels with longstanding versus acute GCA with a mean agreement and kappa values of 81% and 0.63, respectively. CONCLUSION: The new OMERACT ultrasound definition for chronic vasculitis of the AA in GCA revealed a good to excellent inter- and intra-reader reliability in a web-based exercise of experts.

Rheumatologic diseases impact the risk of progression of MGUS to overt multiple myeloma.

Monoclonal gammopathy of undetermined significance (MGUS), a premalignant condition, is associated with various chronic inflammatory rheumatic diseases (RDs) and is frequently observed as an incidental finding during routine work-up. The association of MGUS and chronic RDs is well established, but the impact of RDs on the risk of transformation into overt multiple myeloma (MM) has not been evaluated so far. MGUS patients diagnosed between January 2000 and August 2016 were identified and screened for concomitant RDs. RDs were grouped into antibody (Ab)-mediated RDs and non-Ab-mediated RDs (polymyalgia rheumatica, large-vessel giant cell arteritis, spondyloarthritis, and gout). Progression to MM was defined as a categorical (yes/no) or continuous time-dependent (time to progression) variable. Of 2935 MGUS patients, 255 (9%) had a concomitant RD. MGUS patients diagnosed with non-Ab-mediated RDs had a doubled risk of progression compared with those without a concomitant RD (hazard ratio, 2.1; 95% CI, 1.1-3.9; P = .02). These data translate into a 5-year risk of progression of 4% in MGUS patients without rheumatologic comorbidity, 10% in those with concomitant non-Ab-mediated RDS, and 2% in those with Ab-mediated RDs. By using the complex risk stratification model that includes myeloma protein (M-protein) concentration, immunoglobulin type, and level of free light chain ratio as variables, patients with non-Ab-mediated RDs (n = 57) had the highest risk for progression (hazard ratio, 6.8; 95% CI, 1.5-30.7; P = .01) compared with patients with Ab-mediated RDs (n = 77). Chronic inflammatory diseases have an impact on the risk of MGUS progressing into overt MM, with a doubled risk of transformation observed in patients with non-Ab-mediated RDs. Future research can elucidate whether comorbidities such as RDs should be included in currently applied prognostic MGUS scores.

High expression of mTOR signaling in granulomatous lesions is not predictive for the clinical course of sarcoidosis.

INTRODUCTION: Sarcoidosis is a systemic granulomatous disease with a variable clinical presentation and disease course. There is still no reliable biomarker available, which assists in the diagnosis or prediction of the clinical course. According to a murine model, the expression level of the metabolic checkpoint kinase mechanistic target of Rapamycin complex 1 (mTORC1) in granulomas of sarcoidosis patients may be used as a clinical biomarker. MATERIAL AND METHODS: This is a retrospective analysis of 58 patients with histologically confirmed sarcoidosis. Immunohistochemical staining of granulomas from tissue samples was evaluated for the expression of activated mTORC1 signaling, including phosphorylated mTOR, its downstream effectors S6K1, 4EBP1 and the proliferation marker Ki-67. Patients were categorized according to different clinical phenotypes, serum biomarkers, and immunomodulatory therapy. RESULTS: All patients showed activated mTORC1 signaling in granulomas, which correlated with its downstream effectors S6K1 and 4EBP1 but was not related to Ki-67 expression. The mTORC1 activity revealed an association neither to disease severity nor the necessity of treatment; however, p-mTOR inversely correlated with cumulative corticosteroid dosage. CONCLUSION: Our data confirm activation of the mTORC1 pathway in sarcoidosis, supporting the hypothesis that mTOR is a significant driver in granuloma formation. However, we could not find a relationship between the degree of mTOR activation and disease severity or the need for therapy.

Prevalence and prognostic factors for aortic dilatation in giant cell arteritis - a longitudinal study.

OBJECTIVES: Predictive data for the development of aortic dilatation (AD) in giant-cell arteritis (GCA) are controversial. The aim was to investigate by computed tomography (CT) the prevalence of AD in a consecutive cohort of GCA patients and controls, and to identify possible predictors for AD. METHODS: GCA patients and controls were identified by electronic search and underwent aortic contrast enhanced CT defining AD by aortic diameter adjusted to age, gender and body surface area. Pulse-wave velocity, intima-media thickness (IMT) and laboratory studies including lymphocyte subsets were conducted identifying potential factors associated with AD. Clinical and laboratory parameters at disease onset, occurrence of aortic rupture/dissection before and up to five years after study visit were retrieved by chart review. RESULTS: 144 GCA patients and 115 controls were included. GCA patients developed more frequently AD of the ascending and thoracic descending aorta compared to controls (OR 2.60, p = 0.016; OR 3.65, p = 0.005, respectively). Factors associated with AD development of thoracic descending aorta, but not of the ascending aorta, were higher percentages of circulating CD3+CD4+ cells, higher CD4/CD8 ratio, presence of polymyalgia rheumatica and increased carotid IMT at disease onset (OR range 1.10-3.11, all with p < 0.05). During follow-up, no GCA patient required surgical aortic repair or suffered aortic rupture/dissection. CONCLUSIONS: Thoracic but not abdominal ADs occur more commonly in GCA patients, however, the subsequent risk for aortic repair, rupture or dissection is low. Changes of T-cell subsets, presence of polymyalgia rheumatica and increased carotid IMT at disease onset are associated with AD development.