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RMD Open Sep 2023Evaluation of endothelial dysfunction, lipid metabolism, prevalence and development of cardiovascular diseases in patients with giant cell arteritis (GCA).
OBJECTIVES
Evaluation of endothelial dysfunction, lipid metabolism, prevalence and development of cardiovascular diseases in patients with giant cell arteritis (GCA).
METHODS
138 GCA patients and 100 controls were evaluated for prevalent cardiovascular diseases in 2012. Cholesterol, lipoproteins and triglycerides, intima-media thickness, arterial stiffness, asymmetric and symmetric dimethylarginine were also measured in 2012. Cardiovascular events, mortality and relapse were retrieved by chart review in 2020.
RESULTS
Prevalent carotid and vertebral artery disease was higher in GCA patients than in controls (p<0.001). GCA patients had higher levels of total cholesterol, low-density lipoprotein (LDL), intermediate-density lipoprotein, high-density lipoprotein, apolipoprotein A1 and B, and augmentation index (all with p<0.05). Target LDL levels were less frequently achieved at study inclusion by GCA patients (p=0.001), who developed more frequently new cardiovascular events, also with a higher amount, during follow-up (all with p<0.001). Statin treatment in GCA patients was associated with lower levels of asymmetric dimethylarginine, monocytes and C reactive protein (all with p<0.05). Relapse was independently associated with higher risk of future cardiovascular events (OR 5.01 (95% CI 1.55 to 16.22), p=0.007).
CONCLUSIONS
GCA patients are at a high risk of developing cardiovascular diseases. Of relevance, there was underuse of statins and a large proportion of these patients showed LDL cholesterol concentrations above the treatment targets for high-risk patients. These data underscore the need for improvement of preventive strategies to reduce cardiovascular risk in GCA patients.
Topics: Humans; Cardiovascular Diseases; Giant Cell Arteritis; Carotid Intima-Media Thickness; C-Reactive Protein; Hydroxymethylglutaryl-CoA Reductase Inhibitors
PubMed: 37657846
DOI: 10.1136/rmdopen-2023-003481 -
Annals of the Rheumatic Diseases Mar 2024Ageing and inflammation are associated with clonal haematopoiesis (CH), the emergence of somatic mutations in haematopoietic cells. This study details CH in patients...
OBJECTIVES
Ageing and inflammation are associated with clonal haematopoiesis (CH), the emergence of somatic mutations in haematopoietic cells. This study details CH in patients with systemic vasculitis in association with clinical, haematological and immunological parameters.
METHODS
Patients with three forms of vasculitis were screened for CH in peripheral blood by error-corrected sequencing. Relative contributions of age and vasculitis on CH prevalence were calculated using multivariable logistic regression. Clonal hierarchies were assessed by proteogenomic single-cell DNA sequencing, and functional experiments were performed in association with CH status.
RESULTS
Patients with Takayasu's arteritis (TAK; n=70; mean age=33.2 years), antineutrophil cytoplasmic antibody-associated vasculitis (AAV; n=47; mean age=55.3 years) and giant cell arteritis (GCA; n=59; mean age=71.2 years) were studied. CH, most commonly in and was detected in 34% (60/176) of patients versus 18% (28/151) of age-matched controls (p<0.01). Prevalence of CH was independently associated with age (standardised B=0.96, p<0.01) and vasculitis (standardised B=0.46, p<0.01), occurring in 61%, 32% and 13% of patients with GCA, AAV and TAK, respectively. Both branched and linear clonal trajectories showed myeloid-lineage bias, and CH was associated with markers of cellular activation. In GCA, mutations were detected in temporal artery biopsies, and clinical relapse correlated with CH in a dose-dependent relationship with clone size.
CONCLUSIONS
Age was more strongly associated with CH prevalence than inflammation in systemic vasculitis. Clonal profile was dominated by mutations which were associated with relapse in GCA. CH is not likely a primary causal factor in systemic vasculitis but may contribute to inflammation.
Topics: Humans; Adult; Middle Aged; Aged; Giant Cell Arteritis; Takayasu Arteritis; Clonal Hematopoiesis; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Inflammation; Recurrence
PubMed: 38049983
DOI: 10.1136/ard-2023-224933 -
Autoimmunity Reviews Sep 2023To investigate the clinicopathologic features of patients with giant cell arteritis (GCA) who had thoracic aorta aneurysm or dissection surgery. (Review)
Review
OBJECTIVES
To investigate the clinicopathologic features of patients with giant cell arteritis (GCA) who had thoracic aorta aneurysm or dissection surgery.
METHODS
Patients who had thoracic aorta surgery between January 1, 2000, and December 31, 2021, at the Mayo Clinic, Rochester, Minnesota, were identified with current procedural terminology (CPT) codes. The identified patients were screened for a prior diagnosis of GCA with diagnostic codes and electronic text search. The available medical records of all the patients of interest were manually reviewed. Thoracic aorta tissues obtained during surgery were re-evaluated in detail by pathologists. The clinicopathologic features of these patients were analyzed. Overall observed survival was compared with lifetable rates from the United States population.
RESULTS
Of the 4621 patients with a CPT code for thoracic aorta surgery, 49 had a previous diagnosis of GCA. Histopathologic evaluation of the aortic tissue revealed active aortitis in most patients with GCA (40/49, 82%) after a median (IQR) of 6.0 (2.6-10.3) years from GCA diagnosis. All patients were considered in clinical remission at the time of aortic surgery. The overall mortality compared to age and sex-matched general population was significantly increased with a standardized mortality ratio of 1.55 (95% CI, 1.05-2.19).
CONCLUSION
Histopathologic evaluation of the thoracic aorta obtained during surgery revealed active aortitis in most patients with GCA despite being considered in clinical remission several years after GCA diagnosis. Chronic, smoldering aortic inflammation likely contributes to the development of aortic aneurysm and dissection in GCA.
Topics: Humans; Giant Cell Arteritis; Aortitis; Aorta; Inflammation
PubMed: 37597603
DOI: 10.1016/j.autrev.2023.103411 -
Giant Cell Arteritis: Advances in Understanding Pathogenesis and Implications for Clinical Practice.Cells Jan 2024Giant cell arteritis (GCA) is a noninfectious granulomatous vasculitis of unknown etiology affecting individuals older than 50 years. Two forms of GCA have been... (Review)
Review
Giant cell arteritis (GCA) is a noninfectious granulomatous vasculitis of unknown etiology affecting individuals older than 50 years. Two forms of GCA have been identified: a cranial form involving the medium-caliber temporal artery causing temporal arteritis (TA) and an extracranial form involving the large vessels, mainly the thoracic aorta and its branches. GCA generally affects individuals with a genetic predisposition, but several epigenetic (micro)environmental factors are often critical for the onset of this vasculitis. A key role in the pathogenesis of GCA is played by cells of both the innate and adaptive immune systems, which contribute to the formation of granulomas that may include giant cells, a hallmark of the disease, and arterial tertiary follicular organs. Cells of the vessel wall cells, including vascular smooth muscle cells (VSMCs) and endothelial cells, actively contribute to vascular remodeling responsible for vascular stenosis and ischemic complications. This review will discuss new insights into the molecular and cellular pathogenetic mechanisms of GCA, as well as the implications of these findings for the development of new diagnostic biomarkers and targeted drugs that could hopefully replace glucocorticoids (GCs), still the backbone of therapy for this vasculitis.
Topics: Humans; Giant Cell Arteritis; Endothelial Cells; Glucocorticoids
PubMed: 38334659
DOI: 10.3390/cells13030267 -
Frontiers in Immunology 2023The network of IL-17 cytokines is considered a key component of autoimmune and inflammatory processes. Blocking IL-17 showed great success in psoriasis as well as... (Review)
Review
The network of IL-17 cytokines is considered a key component of autoimmune and inflammatory processes. Blocking IL-17 showed great success in psoriasis as well as psoriatic arthritis, and in patients with axial spondyloarthritis. Secukinumab is one of the approved IL-17A inhibitors for these diseases and is now routinely used. In giant cell arteritis, a large vessel vasculitis, there is accumulating evidence for a pathogenic role of IL-17 and Th17 cells, which are part of the CD4 T-cell subset. Giant cell arteritis occurs in individuals over 50 years of age and many have relative contraindications to glucocorticoid therapy, which today still represents the mainstay therapy. Despite the approval of tocilizumab, which targets the IL-6 receptor, a high demand for glucocorticoid-sparing agents remains that combine the effective suppression of the acute inflammation observed in giant cell arteritis with a safety profile that matches the needs of an older patient population. The first results from a phase II proof-of-principle study (TitAIN) support an optimistic outlook on a potential new treatment option with secukinumab in giant cell arteritis.
Topics: Humans; Middle Aged; Giant Cell Arteritis; Interleukin-17; Glucocorticoids; Cytokines
PubMed: 38299156
DOI: 10.3389/fimmu.2023.1199059 -
RMD Open Nov 2023We aimed to analyse the association between infections and the subsequent risk of giant cell arteritis (GCA) and/or polymyalgia rheumatica (PMR) by a systematic review... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
We aimed to analyse the association between infections and the subsequent risk of giant cell arteritis (GCA) and/or polymyalgia rheumatica (PMR) by a systematic review and a meta-analysis of observational studies.
METHODS
Two databases (Medline and Embase) were systematically reviewed. Epidemiological studies studying the association between any prior infection and the onset of GCA/PMR were eligible. Risk of bias was assessed using the Newcastle-Ottawa quality assessment scale. Outcomes and pooled statistics were reported as OR and their 95% CI.
RESULTS
Eleven studies (10 case-control studies and one cohort study) were analysed, seven of them were included in the meta-analysis. Eight were at low risk of bias. A positive and significant association was found between prior overall infections and prior (HZ) infections with pooled OR (95% CI) of 1.27 (1.18 to 1.37) and 1.20 (1.08 to 1.21), respectively. When analysed separately, hospital-treated and community-treated infections, were still significantly associated with the risk of GCA, but only when infections occurring within the year prior to diagnosis were considered (pooled OR (95% CI) 1.92 (1.67 to 2.21); 1.67 (1.54 to 1.82), respectively). This association was no longer found when infections occurring within the year prior to diagnosis were excluded.
CONCLUSION
Our study showed a positive association between the risk of GCA and prior overall infections (occurring in the year before), and prior HZ infections. Infections might be the reflect of an altered immunity of GCA patients or trigger the disease. However, reverse causation cannot be excluded.CRD42023404089.
Topics: Humans; Giant Cell Arteritis; Polymyalgia Rheumatica; Cohort Studies; Case-Control Studies
PubMed: 37949615
DOI: 10.1136/rmdopen-2023-003493 -
Circulation Journal : Official Journal... Dec 2023Takayasu arteritis (TAK) is a rare disease characterized by inflammation of large blood vessels, which results in vascular stenosis, occlusion, and aneurysm formation....
Takayasu arteritis (TAK) is a rare disease characterized by inflammation of large blood vessels, which results in vascular stenosis, occlusion, and aneurysm formation. The principal treatment has been glucocorticoids, but the recent emergence of biological disease-modifying anti-rheumatic drugs (bDMARDs), represented by tocilizumab (TCZ), has significantly changed the treatment landscape. Both cardiologists and cardiovascular surgeons will encounter patients receiving these drugs who require catheterization, other invasive procedures, or surgery. Several bDMARDs have shown promise against TAK in clinical studies and their use is expected to increase in the future. Janus kinase inhibitors may also be effective. Here, we review the evidence supporting the use of TCZ and other immunosuppressants in TAK and provides an update on their status as well as the relevant guidelines.
PubMed: 38123294
DOI: 10.1253/circj.CJ-23-0780 -
Cardiovascular Pathology : the Official... 2023Giant cell arteritis (GCA) is the most common systemic vasculitis in adults in Europe and North America, typically involving the extra-cranial branches of the carotid...
Giant cell arteritis (GCA) is the most common systemic vasculitis in adults in Europe and North America, typically involving the extra-cranial branches of the carotid arteries and the thoracic aorta. Despite advances in noninvasive imaging, temporal artery biopsy (TAB) remains the gold standard for establishing a GCA diagnosis. The processing of TAB depends largely on individual institutional protocol, and the interpretation and reporting practices vary among pathologists. To address this lack of uniformity, the Society for Cardiovascular Pathology formed a committee tasked with establishing consensus guidelines for the processing, interpretation, and reporting of TAB specimens, based on the existing literature. This consensus statement includes a discussion of the differential diagnoses including other forms of arteritis and noninflammatory changes of the temporal artery.
PubMed: 37683739
DOI: 10.1016/j.carpath.2023.107574 -
Seminars in Arthritis and Rheumatism Dec 2023Prompt diagnosis and treatment of polymyalgia rheumatica (PMR) is crucial to prevent long-term complications and improve patient outcomes. However, there is currently no... (Review)
Review
INTRODUCTION
Prompt diagnosis and treatment of polymyalgia rheumatica (PMR) is crucial to prevent long-term complications and improve patient outcomes. However, there is currently no standardized approach to referral of suspected PMR patients to rheumatologists, leading to inconsistent management practices. The objective of this systematic review was to clarify the existing evidence regarding the following aspects of early management strategies in patients with suspected PMR: diagnostic strategies, GCA screening, glucocorticoid initiation prior to referral, value of shared care and value of fast track clinic.
METHODS
Two authors performed a systematic literature search, data extraction and risk of bias assessment independently. The literature search was conducted in Embase, MEDLINE (PubMed) and Cochrane. Studies were included if they contained cohorts of suspected PMR patients and evaluated the efficacy of different diagnostic strategies for PMR, screening for giant cell arteritis (GCA), starting glucocorticoids before referral to secondary care, shared care, or fast-track clinics.
RESULTS
From 2,437 records excluding duplicates, 14 studies met the inclusion criteria. Among these, 10 studies investigated the diagnostic accuracy of various diagnostic strategies with the majority evaluating different clinical approaches, but none of them showed consistently high performance. However, 4 studies on shared care and fast-track clinics showed promising results, including reduced hospitalization rates, lower starting doses of glucocorticoids, and faster PMR diagnosis.
CONCLUSION
This review emphasizes the sparse evidence of early management and referral strategies for patients with suspected PMR. Additionally, screening and diagnostic strategies for differentiating PMR from other diseases, including concurrent GCA, require clarification. Fast-track clinics may have potential to aid patients with PMR in the future, but studies will be needed to determine the appropriate pre-referral work-up.
Topics: Humans; Giant Cell Arteritis; Polymyalgia Rheumatica; Glucocorticoids; Referral and Consultation
PubMed: 37639896
DOI: 10.1016/j.semarthrit.2023.152260 -
Human Vaccines & Immunotherapeutics Dec 2024We conducted a national in-depth analysis including pharmacovigilance reports and clinical study to assess the reporting rate (RR) and to determine the clinical profile...
We conducted a national in-depth analysis including pharmacovigilance reports and clinical study to assess the reporting rate (RR) and to determine the clinical profile of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) in COVID-19-vaccinated individuals. First, based on the French pharmacovigilance database, we estimated the RR of PMR and GCA cases in individuals aged over 50 who developed their initial symptoms within one month of receiving the BNT162b2 mRNA, mRNA-1273, ChAdOx1 nCoV-19, and Ad26.COV2.S vaccines. We then conducted a nationwide survey to gather clinical profiles, therapeutic management, and follow-up data from individuals registered in the pharmacovigilance study. A total of 70 854 684 COVID-19 vaccine doses were administered to 25 260 485 adults, among which, 179 cases of PMR (RR 7. 1 cases/1 000 000 persons) and 54 cases of GCA (RR 2. 1 cases/1 000 000 persons) have been reported. The nationwide survey allowed the characterization of 60 PMR and 35 GCA cases. Median time to the onset of first symptoms was 10 (range 2-30) and 7 (range 2-25) days for PMR and GCA, respectively. Phenotype, GCA-related ischemic complications and -large vessel vasculitis as well as therapeutic management and follow-up seemed similar according to the number of vaccine shots received and when compared to the literature data of unvaccinated population. Although rare, the short time between immunization and the onset of first symptoms of PMR and GCA suggests a temporal association. Physician should be aware of this potential vaccine-related phenomenon.
Topics: Adult; Humans; Middle Aged; Giant Cell Arteritis; Polymyalgia Rheumatica; COVID-19 Vaccines; Ad26COVS1; BNT162 Vaccine; ChAdOx1 nCoV-19; COVID-19; Vaccination
PubMed: 38563792
DOI: 10.1080/21645515.2024.2334084