Inflammation mediates approximately one quarter of excess relative all-cause mortality in persons with rheumatoid arthritis: the Trøndelag Health Study

Videm, Vibeke; Houge, Ingrid Sæther; Liff, Marthe Halsan

doi:10.1038/s41598-022-21977-9

Cited by 7 publications

(12 citation statements)

References 33 publications

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“…After a full-text review of the remaining 51 articles, a further 14 were excluded because of missing data (n=4), duplicate data (n=4), incorrect study design (n=3), non-English language used (n=2), and inclusion of children or adolescents (n=1). Therefore, 37 studies (43 study groups, 34 investigating plasma/serum, seven urine, one saliva, and one synovial fluid) were selected for analysis ( Table 1 ) ( 54 – 90 ).…”

Section: Resultsmentioning

confidence: 99%

“…Thirty studies (34 study groups) reported serum or plasma neopterin concentrations in a total of 2,618 RD patients (mean age 43 years, 32% males) and 5,318 healthy controls (mean age 42 years, 47% males) ( 55 , 59 , 61 , 64 – 67 , 69 – 87 , 89 , 90 ).…”

Section: Resultsmentioning

confidence: 99%

“…Twenty studies were conducted in Asia ( 55 , 59 , 65 , 66 , 69 , 70 , 72 – 74 , 77 , 78 , 80 – 82 , 84 – 89 ), six in Europe ( 61 , 62 , 64 , 67 , 79 , 90 ), three in Africa ( 71 , 75 , 83 ), and the remaining one in America ( 76 ). Ten study groups included patients with RA ( 55 , 76 , 78 – 81 , 83 , 86 , 89 , 90 ), nine with SLE ( 55 , 65 , 70 , 71 , 75 – 77 , 82 , 84 ), eight with BD ( 59 , 65 , 66 , 69 , 72 – 74 , 87 ), three with IIM ( 62 , 88 ), two with pSS ( 64 , 67 ), one with SSc ( 61 ), and one with AS ( 85 ). The analytical methods used for measuring neopterin included an enzyme-linked immunosorbent assay (ELISA) in 18 studies ( 61 , 64 – 67 , 69 – 71 , 74 – 76 , 78 , 79 , 81 , 85 , 86 ,...…”

Section: Resultsmentioning

confidence: 99%

“…Ten study groups included patients with RA ( 55 , 76 , 78 – 81 , 83 , 86 , 89 , 90 ), nine with SLE ( 55 , 65 , 70 , 71 , 75 – 77 , 82 , 84 ), eight with BD ( 59 , 65 , 66 , 69 , 72 – 74 , 87 ), three with IIM ( 62 , 88 ), two with pSS ( 64 , 67 ), one with SSc ( 61 ), and one with AS ( 85 ). The analytical methods used for measuring neopterin included an enzyme-linked immunosorbent assay (ELISA) in 18 studies ( 61 , 64 – 67 , 69 – 71 , 74 – 76 , 78 , 79 , 81 , 85 , 86 , 88 , 90 ), liquid chromatography with fluorimetric detection in 10 ( 55 , 72 , 73 , 77 , 80 , 82 – 84 , 87 , 89 ), and radioimmunoassay in two ( 59 , 62 ). Serum was analysed in 26 studies ( 55 , 59 , 61 , 62 , 64 – 67 , 69 – 74 , 76 – 78 , 81 …”

Section: Resultsmentioning

confidence: 99%

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A systematic review and meta-analysis of neopterin in rheumatic diseases

Mangoni,

Zinellu

2023

Front. Immunol.

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IntroductionNovel biomarkers of inflammation and oxidative stress might enhance the early recognition, management, and clinical outcomes of patients with rheumatic diseases (RDs). We assessed the available evidence regarding the pathophysiological role of neopterin, the oxidation product of 7,8-dihydroneopterin, a pteridine generated in macrophages activated by interferon-γ, by conducting a systematic review and meta-analysis of studies reporting its concentrations in biological fluids in RD patients and healthy controls.MethodsWe searched electronic databases for relevant articles published between inception and 31 August 2023. The risk of bias and the certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist and the Grades of Recommendation, Assessment, Development and Evaluation Working Group system, respectively.ResultsIn 37 studies, when compared to healthy controls, RD patients had significantly higher concentrations of neopterin both in plasma or serum (standard mean difference, SMD=1.31, 95% CI 1.01 to 1.61; p<0.001; moderate certainty of evidence) and in the urine (SMD=1.65, 95% CI 0.86 to 2.43, p<0.001; I2 = 94.2%, p<0.001; low certainty of evidence). The results were stable in sensitivity analysis. There were non-significant associations in meta-regression and subgroup analysis between the effect size and age, male to female ratio, year of publication, sample size, RD duration, C-reactive protein, erythrocyte sedimentation rate, specific type of RD, presence of connective tissue disease, analytical method used, or biological matrix investigated (plasma vs. serum). By contrast, the effect size was significantly associated with the geographical area in studies assessing serum or plasma and with the type of RD in studies assessing urine.DiscussionPending additional studies that also focus on early forms of disease, our systematic review and meta-analysis supports the proposition that neopterin, a biomarker of inflammation and oxidative stress, can be useful for the identification of RDs. (PROSPERO registration number: CRD42023450209).Systematic review registrationPROSPERO, identifier CRD42023450209

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

A systematic review and meta-analysis of neopterin in rheumatic diseases

Mangoni,

Zinellu

2023

Front. Immunol.

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“…[5] Moreover, inflammation itself is responsible for up to a fourth of mortalities in patients with RA. [9] Therefore, treatment strategies for RA need to consider the complex pathophysiology unique to immune-mediated inflammatory diseases in a multifaceted manner.…”

Section: Introductionmentioning

confidence: 99%

Integrative medicine using East Asian herbal medicine for inflammatory pain in patients with rheumatoid arthritis: A protocol for systematic review and meta-analysis integrated with multiple data mining for core candidate discovery

Jo¹,

Seo²,

Baek³

et al. 2023

Medicine

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Background: Rheumatoid arthritis is a chronic inflammatory autoimmune disease characterized by a wide range of clinical symptoms affecting various bodily functions, including skeletal, vascular, metabolic, and cognitive functions. This review aimed to evaluate the efficacy and safety of integrative medicine (East Asian herbal medicine combined with conventional medicine) used for the treatment of inflammatory pain in rheumatoid arthritis and to identify key candidate drugs based on the data. Methods: A comprehensive literature search will be conducted in 4 core databases (PubMed, Excerpta Medica database, Cochrane Library, and Cumulative Index to Nursing & Allied Health Literature) 4 Korean databases (Oriental Medicine Advanced Searching Integrated System, Korean Studies Information Service System, Research Information Service System, and Korea Citation Index), 2 Chinese databases (Chinese National Knowledge Infrastructure Database and Wanfang data), and 1 Japanese database (Citation Information by National Institute of Informatics) for randomized controlled trials from December 13, 2022. Statistical analysis will be performed using R version 4.1.2 and R Studio program. The American College of Rheumatology 20/50/70 score and rate of adverse events will be the primary outcomes. All outcomes will be analyzed using a random-effects model to produce more statistically conservative results. Sensitivity, meta-regression, and subgroup analyses will be used to identify the sources of any heterogeneity in the study. The revised tool for assessing the risk of bias in randomized trials, version 2.0, will be used to evaluate methodological quality. The overall quality of evidence will be assessed according to the Grading of Recommendations Assessment, Development, and Evaluation Pro Framework. Ethics and dissemination: There are no ethical issues, as no primary data will be collected directly from the participants. The results of this review will be reported in a peer-reviewed scientific journal. Trial registration: PROSPERO registration number: CRD42023412385.

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Relative importance of inflammation and cardiorespiratory fitness for all-cause mortality risk in persons with rheumatoid arthritis: the population-based Trøndelag Health Study

Videm

Liff

2023

RMD Open

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ObjectiveInflammation and reduced cardiorespiratory fitness (CRF) are associated with increased mortality rates in rheumatoid arthritis (RA). We aimed at directly comparing the relative importance of inflammation and reduced CRF as mediators of all-cause mortality in persons with RA compared with controls, quantifying direct and indirect (mediated) effects.MethodsPersons with (n=223, cases) and without (n=31 684, controls) RA from the third survey of the Trøndelag Health Study (HUNT3, 2006–2008) were included. Inflammation was quantified using C reactive protein (CRP) and estimated CRF (eCRF) was calculated using published formulae. All-cause mortality was found by linkage to the Norwegian Cause of Death Registry, with follow-up from inclusion in HUNT3 until death or 31 December 2018. Data were analysed using standardised equation modelling, permitting complex correlations among variables.ResultsPersons with RA had increased all-cause mortality rates (24.1% vs 9.9%, p<0.001). Both eCRF (p<0.001) and CRP ≥3 mg/L (p<0.001) were mediators of this excess mortality, rendering the direct effect of RA non-significant (p=0.19). The indirect effect of RA mediated by eCRF (standardised coefficient 0.006) was approximately three times higher than the indirect effect mediated by CRP (standardised coefficient 0.002) in a model adjusted for other mortality risk factors.ConclusionEven with CRP concentrations <3 mg/L in all patients with RA, excess mortality mediated by low CRF would still play an important role. Improved inflammation control in RA does not necessarily lead to better CRF. Therefore, our study strongly supports recommendations for development and implementation of exercise programmes aimed at improving CRF in persons with RA.

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Inflammation mediates approximately one quarter of excess relative all-cause mortality in persons with rheumatoid arthritis: the Trøndelag Health Study

Cited by 7 publications

References 33 publications

A systematic review and meta-analysis of neopterin in rheumatic diseases

A systematic review and meta-analysis of neopterin in rheumatic diseases

Integrative medicine using East Asian herbal medicine for inflammatory pain in patients with rheumatoid arthritis: A protocol for systematic review and meta-analysis integrated with multiple data mining for core candidate discovery

Relative importance of inflammation and cardiorespiratory fitness for all-cause mortality risk in persons with rheumatoid arthritis: the population-based Trøndelag Health Study

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