Increased risk of cardiovascular disease in giant cell arteritis: a general population–based study
TL;DR: General population-based evidence is provided that GCA patients are at a substantially increased risk of cardiovascular disease and increased monitoring for this potentially fatal outcome and its modifiable risk factors is warranted for G CA patients.
Abstract: Objective To determine the risk of newly recorded myocardial infarction (MI) and stroke among incident GCA cases compared with controls from the general population. We also evaluated time trends during follow-up. Methods We conducted a matched cohort study (1996-2010) of all patients with incident GCA from the province of British Columbia, Canada. We estimated incidence rates of MI and stroke according to GCA disease duration. We calculated hazard ratios (HRs), adjusting for potential confounders. Results Among 809 individuals with GCA (mean age 75.9 years, 75.8% female), 83 developed MI and 60 developed stroke, with corresponding incidence rates of 38.1 and 26.4/1000 person-years, respectively. Compared with non-GCA cases, the age-, sex- and entry time-matched HRs were 2.75 (95% CI 2.16, 3.50) for MI and 2.21 (95% CI 1.68, 2.91) for stroke. When other covariates were adjusted for, the corresponding HRs were 1.77 (95% CI 1.29, 2.43) and 2.04 (95% CI 1.43, 2.93). The age-, sex- and entry time-matched HRs for MI and stroke were highest during the first year after GCA diagnosis [4.76 (95% CI 3.29, 6.88) and 3.20 (95% CI 2.11, 4.87), respectively]. Conclusion These findings provide general population-based evidence that GCA patients are at a substantially increased risk of cardiovascular disease. Increased monitoring for this potentially fatal outcome and its modifiable risk factors is warranted for GCA patients.
Citations
More filters
TL;DR: The feasibility of providing training in ultrasound for the diagnosis of giant cell arteritis has been demonstrated and the results indicate better sensitivity but poorer specificity of ultrasound compared with biopsy and suggest some scope for reducing the role of biopsy.
Abstract: Background: Giant cell arteritis (GCA) is a relatively common form of primary systemic vasculitis, which, if left untreated, can lead to permanent sight loss. We compared ultrasound as an alternative diagnostic test with temporal artery biopsy, which may be negative in 9–61% of true cases.
Objective: To compare the clinical effectiveness and cost-effectiveness of ultrasound with biopsy in diagnosing patients with suspected GCA.
Design: Prospective multicentre cohort study.
Setting: Secondary care.
Participants: A total of 381 patients referred with newly suspected GCA.
Main outcome measures: Sensitivity, specificity and cost-effectiveness of ultrasound compared with biopsy or ultrasound combined with biopsy for diagnosing GCA and interobserver reliability in interpreting scan or biopsy findings.
Results: We developed and implemented an ultrasound training programme for diagnosing suspected GCA. We recruited 430 patients with suspected GCA. We analysed 381 patients who underwent both ultrasound and biopsy within 10 days of starting treatment for suspected GCA and who attended a follow-up assessment (median age 71.1 years; 72% female). The sensitivity of biopsy was 39% [95% confidence interval (CI) 33% to 46%], which was significantly lower than previously reported and inferior to ultrasound (54%, 95% CI 48% to 60%); the specificity of biopsy (100%, 95% CI 97% to 100%) was superior to ultrasound (81%, 95% CI 73% to 88%). If we scanned all suspected patients and performed biopsies only on negative cases, sensitivity increased to 65% and specificity was maintained at 81%, reducing the need for biopsies by 43%. Strategies combining clinical judgement (clinician’s assessment at 2 weeks) with the tests showed sensitivity and specificity of 91% and 81%, respectively, for biopsy and 93% and 77%, respectively, for ultrasound; cost-effectiveness (incremental net monetary benefit) was £485 per patient in favour of ultrasound with both cost savings and a small health gain. Inter-rater analysis revealed moderate agreement among sonographers (intraclass correlation coefficient 0.61, 95% CI 0.48 to 0.75), similar to pathologists (0.62, 95% CI 0.49 to 0.76).
Limitations: There is no independent gold standard diagnosis for GCA. The reference diagnosis used to determine accuracy was based on classification criteria for GCA that include clinical features at presentation and biopsy results.
Conclusion: We have demonstrated the feasibility of providing training in ultrasound for the diagnosis of GCA. Our results indicate better sensitivity but poorer specificity of ultrasound compared with biopsy and suggest some scope for reducing the role of biopsy. The moderate interobserver agreement for both ultrasound and biopsy indicates scope for improving assessment and reporting of test results and challenges the assumption that a positive biopsy always represents GCA.
Future work: Further research should address the issue of an independent reference diagnosis, standards for interpreting and reporting test results and the evaluation of ultrasound training, and should also explore the acceptability of these new diagnostic strategies in GCA.
Funding: he National Institute for Health Research Health Technology Assessment programme.
324 citations
Additional excerpts
...Health technology assessment (Winchester, England), 20 (90)....
[...]
TL;DR: The recommendations, which will be updated regularly, are intended to guide and harmonize the standards of GCA management.
Abstract: Purpose Management of giant cell arteritis (GCA, Horton's disease) involves many uncertainties. This work was undertaken to establish French recommendations for GCA management. Methods Recommendations were developed by a multidisciplinary panel of 33 physicians, members of the French Study Group for Large Vessel Vasculitis (Groupe d’etude francais des arterites des gros vaisseaux [GEFA]). The topics to be addressed, selected from proposals by group members, were assigned to subgroups to summarize the available literature and draft recommendations. Following an iterative consensus-seeking process that yielded consensus recommendations, the degree of agreement among panel members was evaluated with a 5-point Likert scale. A recommendation was approved when ≥ 80% of the voters agreed or strongly agreed. Results The 15 retained topics resulted in 31 consensus recommendations focusing on GCA nomenclature and classification, the role of temporal artery biopsy and medical imaging in the diagnosis, indications and search modalities for involvement of the aorta and its branches, the glucocorticoid regimen to prescribe, treatment of complicated GCA, indications for use of immunosuppressants or targeted biologic therapies, adjunctive treatment measures, and management of relapse and recurrence. Conclusions The recommendations, which will be updated regularly, are intended to guide and harmonize the standards of GCA management.
163 citations
[...]
TL;DR: Recent reports indicate a possible association of GCA with varicella zoster virus (VZV) and a characteristic pattern of symptoms, physical examination findings, elevated acute-phase reactants (erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP]), biopsy findings, and vascular imaging.
Abstract: This issue provides a clinical overview of giant cell arteritis, focusing on diagnosis, treatment, and practice improvement The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including MKSAP (Medical Knowledge and Self-Assessment Program) Annals of Internal Medicine editors develop In the Clinic in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of additional science writers and physician writers
59 citations
TL;DR: Patients with GCA have higher rates of selected comorbidities, including severe infections, compared with a reference population, emphasizing the unmet need to find alternative treatments for GCA.
Abstract: Objective. To compare the rate of occurrence of comorbidities, including severe infections, in a population-based cohort of patients with biopsy-proven giant cell arteritis (GCA) with a reference population in Southern Sweden. Methods. The study included a population-based cohort of biopsy-proven GCA cases diagnosed between 1998 and 2010 from the Skane region in Southern Sweden (population: 1.2 million). For each patient, 4 reference subjects were identified from the general population and matched for age, sex, area of residence, and date of diagnosis of GCA. Using the Skane Healthcare Register, comorbidities and severe infections (requiring hospitalization) diagnosed after GCA onset were identified. The rate of the first occurrence of each comorbidity was the result of dividing the number of subjects with a given comorbidity by the person-years of followup. The rate ratio (RR; GCA:reference population) was also calculated. Results. There were 768 patients (571 women) with GCA and 3066 reference persons included in the study. The RR were significantly elevated for osteoporosis (2.81, 95% CI 2.33–3.37), followed by venous thromboembolic diseases (2.36, 95% CI 1.61–3.40), severe infections (1.85, 95% CI 1.57–2.18), thyroid diseases (1.55, 95% CI 1.25–1.91), cerebrovascular accidents (1.40, 95% CI 1.12–1.74), and diabetes mellitus (1.29, 95% CI 1.05–1.56). The RR for ischemic heart disease was elevated, but did not reach statistical significance (1.20, 95% CI 1.00–1.44). Conclusion. Patients with GCA have higher rates of selected comorbidities, including severe infections, compared with a reference population. Several of these comorbidities may be related to treatment with glucocorticosteroids, emphasizing the unmet need to find alternative treatments for GCA.
44 citations
TL;DR: The study indicates a significantly increased risk of CVA among patients with GCA, with a pooled risk ratio of 1.40 (95% CI: 1.27-1.56) and the statistical heterogeneity was low with an I2 of 31%.
44 citations
References
More filters
TL;DR: The method of classifying comorbidity provides a simple, readily applicable and valid method of estimating risk of death fromComorbid disease for use in longitudinal studies and further work in larger populations is still required to refine the approach.
39,961 citations
TL;DR: Innate as well as adaptive immune responses have been identified in atherosclerosis, with components of cholesterol-carrying low-density lipoprotein triggering inflammation, T cell activation and antibody production during the course of disease.
Abstract: Cardiovascular disease, a leading cause of mortality worldwide, is caused mainly by atherosclerosis, a chronic inflammatory disease of blood vessels. Lesions of atherosclerosis contain macrophages, T cells and other cells of the immune response, together with cholesterol that infiltrates from the blood. Targeted deletion of genes encoding costimulatory factors and proinflammatory cytokines results in less disease in mouse models, whereas interference with regulatory immunity accelerates it. Innate as well as adaptive immune responses have been identified in atherosclerosis, with components of cholesterol-carrying low-density lipoprotein triggering inflammation, T cell activation and antibody production during the course of disease. Studies are now under way to develop new therapies based on these concepts of the involvement of the immune system in atherosclerosis.
1,934 citations
TL;DR: In this article, a meta-analysis of observational studies was conducted to determine the magnitude of risk of cardiovascular mortality in patients with rheumatoid arthritis (RA) compared with the general population.
Abstract: Objective
To determine the magnitude of risk of cardiovascular mortality in patients with rheumatoid arthritis (RA) compared with the general population through a meta-analysis of observational studies.
Methods
We searched Medline, EMBase, and Lilacs databases from their inception to July 2005. Observational studies that met the following criteria were assessed by 2 researchers: 1) prespecified RA definition, 2) clearly defined cardiovascular disease (CVD) outcome, including ischemic heart disease (IHD) and cerebrovascular accidents (CVAs), and 3) reported standardized mortality ratios (SMRs) and 95% confidence intervals (95% CIs). We calculated weighted–pooled summary estimates of SMRs (meta-SMRs) for CVD, IHD, and CVAs using the random-effects model, and tested for heterogeneity using the I2 statistic.
Results
Twenty-four studies met the inclusion criteria, comprising 111,758 patients with 22,927 cardiovascular events. Overall, there was a 50% increased risk of CVD death in patients with RA (meta-SMR 1.50, 95% CI 1.39–1.61). Mortality risks for IHD and CVA were increased by 59% and 52%, respectively (meta-SMR 1.59, 95% CI 1.46–1.73 and meta-SMR 1.52, 95% CI 1.40–1.67, respectively). We identified asymmetry in the funnel plot (Egger's test P = 0.002), as well as significant heterogeneity in all main analyses (P < 0.0001). Subgroup analyses showed that inception cohort studies (n = 4, comprising 2,175 RA cases) were the only group that did not show a significantly increased risk for CVD (meta-SMR 1.19, 95% CI 0.86–1.68).
Conclusion
Published data indicate that CVD mortality is increased by ∼50% in RA patients compared with the general population. However, we found that study characteristics may influence the estimate.
1,253 citations
TL;DR: 3 regression approaches for estimating 2 key quantities in competing risks analysis: the cause-specific relative hazard (cs)RH and the subdistribution relative hazard ((sd)RH) and the interpretation of parameters obtained with these methods are outlined.
Abstract: Competing events can preclude the event of interest from occurring in epidemiologic data and can be analyzed by using extensions of survival analysis methods. In this paper, the authors outline 3 regression approaches for estimating 2 key quantities in competing risks analysis: the cause-specific relative hazard ((cs)RH) and the subdistribution relative hazard ((sd)RH). They compare and contrast the structure of the risk sets and the interpretation of parameters obtained with these methods. They also demonstrate the use of these methods with data from the Women's Interagency HIV Study established in 1993, treating time to initiation of highly active antiretroviral therapy or to clinical disease progression as competing events. In our example, women with an injection drug use history were less likely than those without a history of injection drug use to initiate therapy prior to progression to acquired immunodeficiency syndrome or death by both measures of association ((cs)RH = 0.67, 95% confidence interval: 0.57, 0.80 and (sd)RH = 0.60, 95% confidence interval: 0.50, 0.71). Moreover, the relative hazards for disease progression prior to treatment were elevated ((cs)RH = 1.71, 95% confidence interval: 1.37, 2.13 and (sd)RH = 2.01, 95% confidence interval: 1.62, 2.51). Methods for competing risks should be used by epidemiologists, with the choice of method guided by the scientific question.
1,023 citations