Mortality in rheumatoid arthritis. Increased in the early course of disease, in ischaemic heart disease and in pulmonary fibrosis

Young, Adam; Koduri, Gouri; Batley, M.; Kulinskaya, Elena; Gough, Andrew; Norton, Sam; Dixey, Josh

doi:10.1093/rheumatology/kel253

Cited by 310 publications

(237 citation statements)

References 27 publications

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“…Both previous studies that examined the association between smoking and CVD mortality failed to find a significant association 25, 26. In the study from the Mayo clinic 26, current smokers had double the risk of cardiovascular death compared to never smokers, although this finding did not reach statistical significance (HR 1.98 [95% CI 0.93, 4.24]), perhaps because the study was underpowered (603 patients).…”

Section: Discussionmentioning

confidence: 84%

“…An increased risk of all‐cause mortality associated with smoking in patients with RA has been demonstrated in some 7, 10, but not all 8, 25, previous studies. One of the 2 studies which reported no association, the Early Rheumatoid Arthritis Study 25, collected smoking data retrospectively, and data were missing for 37% of patients.…”

Section: Discussionmentioning

confidence: 87%

“…One of the 2 studies which reported no association, the Early Rheumatoid Arthritis Study 25, collected smoking data retrospectively, and data were missing for 37% of patients. The proportion with missing smoking was probably higher in those who had died and so those who were analyzed may have been healthier or at reduced risk of smoking‐related mortality.…”

Section: Discussionmentioning

confidence: 99%

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Smoking‐Related Mortality in Patients With Early Rheumatoid Arthritis: A Retrospective Cohort Study Using the Clinical Practice Research Datalink

Joseph

Movahedi

Dixon

et al. 2016

Arthritis Care & Research

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ObjectiveTo investigate the association between smoking status and smoking cessation with mortality in patients with rheumatoid arthritis (RA).MethodsAn incident cohort of patients with RA was identified using the Clinical Practice Research Datalink, a database of UK primary care electronic medical records. Time‐varying smoking status, years of cessation, and amount smoked were determined from patients' medical records. The date and underlying cause of death were identified by linkage with Office for National Statistics records. The associations between smoking status and smoking cessation with all‐cause and cause‐specific mortality (circulatory disease, all cancers, lung cancer, respiratory disease, and respiratory infection) were investigated using adjusted Cox (all‐cause mortality) and Fine‐Gray (cause‐specific mortality) regression.ResultsThe cohort comprised 5,677 patients (median age 61.4 years, 68% women), with 40% as never smokers, 34% former smokers, and 26% current smokers at baseline. Compared to never smoking, current smoking was associated with an increased risk of all‐cause mortality (hazard ratio 1.98 [95% confidence interval (95% CI) 1.56, 2.53]), and mortality due to circulatory disease (subdistribution hazard ratio [SHR] 1.96 [95% CI 1.33, 2.90]) and lung cancer (SHR 23.2 [95% CI 5.15, 105]). Each year of smoking cessation was associated with a decreased risk of all‐cause mortality (former heavy smokers SHR 0.85 [95% CI 0.77, 0.94], former light smokers SHR 0.90 [95% CI 0.84, 0.97]).ConclusionCurrent smoking is associated with an increased risk of all‐cause, cardiovascular, and lung cancer mortality in patients with RA. Each year of cessation is associated with a reduced risk of all‐cause mortality. This information may prove helpful in smoking cessation programs for patients with RA.

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Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

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Smoking‐Related Mortality in Patients With Early Rheumatoid Arthritis: A Retrospective Cohort Study Using the Clinical Practice Research Datalink

Joseph

Movahedi

Dixon

et al. 2016

Arthritis Care & Research

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“…pact morbidity and mortality (3)(4)(5)(6)(7)(8). Prevalence estimates vary widely depending on the clinical, functional, and radiographic criteria used to define RA-associated ILD (RA-ILD), but generally prevalence ranges from 10% to 40% among patients diagnosed as having RA (1,(9)(10)(11).…”

mentioning

confidence: 99%

Identification of Citrullinated Hsp90 Isoforms as Novel Autoantigens in Rheumatoid Arthritis–Associated Interstitial Lung Disease

Harlow¹,

Rosas²,

Gochuico³

et al. 2013

Arthritis & Rheumatism

124

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Objective Subsets of patients with rheumatoid arthritis (RA) develop extraarticular complications that include interstitial lung disease (ILD). Because standardized algorithms for identification of RA patients at risk of developing clinically significant ILD are lacking, the purpose of this study was to elucidate unique serologic markers of RA‐associated ILD (RA‐ILD). Methods Sera from RA patients with ILD and from RA patients without ILD were used to immunoprecipitate citrullinated and uncitrullinated proteins derived from K562 cell extracts. Mass spectrometry was performed to facilitate identification of citrullinated proteins differentially immunoprecipitated by RA‐ILD patient sera. These candidate proteins were then used as substrate antigens in custom enzyme‐linked immunosorbent assays (ELISAs) for high‐throughput screening of sera obtained from cohorts of patients with RA, RA‐ILD mixed connective tissue disease (MCTD), or idiopathic pulmonary fibrosis (IPF). Results Differential immunoprecipitation and subsequent mass spectrometric sequencing identified citrullinated Hsp90α and citrullinated Hsp90β as candidate autoantigens in patients with RA‐ILD. ELISAs incorporating uncitrullinated and citrullinated isoforms of Hsp90 as substrate antigens demonstrated that sera from patients with RA‐ILD preferentially recognized citrullinated versions of Hsp90 with moderate sensitivity (range 20–30%) and great specificity (>95%) relative to sera derived from patients with RA alone (without ILD), patients with MCTD, or patients with IPF. Conclusion These studies demonstrate the utility of a novel autoantigen discovery method based on differential immunoprecipitation of citrullinated protein extracts. Application of these techniques identified citrullinated versions of Hsp90α and Hsp90β as autoantibody targets distinguishing RA‐ILD from RA without ILD, MCTD, and IPF, suggesting that anti–citrullinated Hsp90α/β autoantibodies may serve as effective biomarkers for the potentially devastating pulmonary manifestations of RA‐ILD.

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“…Connective tissue diseases (CTDs) are systemic autoimmune disorders that typically affect the skin and musculoskeletal system. ILD is an important cause of morbidity and mortality in patients with CTD, 15,16 commonly occurring in patients with systemic sclerosis, rheumatoid arthritis, idiopathic inflammatory myopathies, mixed CTD, Sj€ ogren's syndrome and systemic lupus erythematosus. 17,18 Consensus criteria have recently been proposed for interstitial pneumonia with autoimmune features (IPAF), defined as patients with ILD who have autoimmune features that do not meet criteria for a defined CTD.…”

Section: High Resolution Computed Tomographymentioning

confidence: 99%

Evaluation of patients with fibrotic interstitial lung disease: A Canadian Thoracic Society position statement

Johannson

Kolb

Fell

et al. 2017

Canadian Journal of Respiratory, Critical Care, and Sleep Medic

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Mortality in rheumatoid arthritis. Increased in the early course of disease, in ischaemic heart disease and in pulmonary fibrosis

Cited by 310 publications

References 27 publications

Smoking‐Related Mortality in Patients With Early Rheumatoid Arthritis: A Retrospective Cohort Study Using the Clinical Practice Research Datalink

Smoking‐Related Mortality in Patients With Early Rheumatoid Arthritis: A Retrospective Cohort Study Using the Clinical Practice Research Datalink

Identification of Citrullinated Hsp90 Isoforms as Novel Autoantigens in Rheumatoid Arthritis–Associated Interstitial Lung Disease

Evaluation of patients with fibrotic interstitial lung disease: A Canadian Thoracic Society position statement

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