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Rheumatoid arthritis and cardiovascular disease associations in the UK Biobank.

Rheumatoid arthritis and cardiovascular disease associations in the UK Biobank.
Rheumatoid arthritis and cardiovascular disease associations in the UK Biobank.

Background: this study evaluated observational and causal relationships between rheumatoid arthritis (RA) and cardiovascular disease and imaging phenotypes in the UK Biobank. 

Methods: RA was defined using linked hospital records, self-reported diagnostics, and medication data. Controls were participants without a record of RA. Cardiovascular diseases (CVDs) were defined using linked hospital records over an average of 14 years of prospective follow-up, including: ischaemic heart diseases (IHD), acute myocardial infarction (AMI), atrial fibrillation, any arrhythmia, non-ischaemic cardiomyopathies, pericardial disease, stroke, peripheral vascular disease, and venous thromboembolism. For participants with cardiovascular magnetic resonance (CMR) available as part of the UK Biobank Imaging Study, we considered measures of cardiac structure and function extracted using automated pipelines. Associations of RA with prevalent and incident CVDs were calculated using logistic and Cox regression. Linear regression was used to examine associations with CMR metrics. Models were adjusted for demographic, lifestyle, and clinical confounders. Causal associations were assessed using two-sample Mendelian randomisation. Genetic instruments for RA (22,350 cases and 74,823 controls), nine CVDs (FinnGen, n = 224,737), and 11 CMR phenotypes (UK Biobank) were extracted and associations assessed using inverse-variance weighting with pleiotropy adjustments and multiple testing corrections. 

Results: the analysis included 1,436 RA cases (mean age 59.9 years; 70.6% female) and 476,975 controls (mean age 56.5 years; 54.3% female). Participants with RA lived in more socioeconomically deprived areas (as per the Townsend Deprivation Index), had lower physical activity levels, were more likely to smoke, and had a higher baseline prevalence of CVDs. In fully adjusted models, participants with RA had a significantly higher hazard of multiple incident CVDs, with the greatest risks related to pericardial disease (HR 2.63 (1.85, 3.74)), heart failure (HR 1.68 (1.42, 1.99)), and AMI (HR 1.53 (1.20, 1.96)). Mendelian Randomisation analyses supported causal links between RA and AMI (OR 1.07 (1.02, 1.09), p = 0.009), arrhythmias (OR 1.05 (1.02, 1.06), p = 0.0007), and IHD (OR 1.05 (1.01, 1.06), p = 0.036). No significant associations were identified between RA and CMR phenotypes. 

Conclusions: people with RA have a heightened risk of multiple prevalent and incident CVDs, independent of shared risk factors, with suggestions of causal links with IHD, AMI, and arrhythmias.

Cardiovascular disease, Causal association, Epidemiology, Ischaemic heart disease, Mendelian randomisation, Pericardial disease, Rheumatoid arthritis, Risk factors, UK Biobank
1741-7015
Salaztzi, Janek
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Condurache, Dorina-Gabriela
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D'angelo, Stefania
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Salih, Ahmed M.
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Szabo, Liliana
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Mahmood, Adil
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Curtis, Elizabeth
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Petersen, Steffen E.
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Altmann, Andre
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Frey, Norbert
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Andre, Florian
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Harvey, Nicholas C.
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Raisi-Estabragh, Zahra
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Salaztzi, Janek
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Condurache, Dorina-Gabriela
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D'angelo, Stefania
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Salih, Ahmed M.
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Szabo, Liliana
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Mahmood, Adil
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Curtis, Elizabeth
12aba0c3-1e9e-49ef-a7e9-3247e649cdd6
Petersen, Steffen E.
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Altmann, Andre
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Frey, Norbert
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Andre, Florian
f1effd02-d1d5-49d7-9dbf-09f958ee1bb7
Harvey, Nicholas C.
ce487fb4-d360-4aac-9d17-9466d6cba145
Raisi-Estabragh, Zahra
43c85c5e-4574-476b-80d6-8fb1cdb3df0a

Salaztzi, Janek, Condurache, Dorina-Gabriela, D'angelo, Stefania, Salih, Ahmed M., Szabo, Liliana, Mahmood, Adil, Curtis, Elizabeth, Petersen, Steffen E., Altmann, Andre, Frey, Norbert, Andre, Florian, Harvey, Nicholas C. and Raisi-Estabragh, Zahra (2025) Rheumatoid arthritis and cardiovascular disease associations in the UK Biobank. BMC Medicine, 23 (1), [605]. (doi:10.1186/s12916-025-04431-1).

Record type: Article

Abstract

Background: this study evaluated observational and causal relationships between rheumatoid arthritis (RA) and cardiovascular disease and imaging phenotypes in the UK Biobank. 

Methods: RA was defined using linked hospital records, self-reported diagnostics, and medication data. Controls were participants without a record of RA. Cardiovascular diseases (CVDs) were defined using linked hospital records over an average of 14 years of prospective follow-up, including: ischaemic heart diseases (IHD), acute myocardial infarction (AMI), atrial fibrillation, any arrhythmia, non-ischaemic cardiomyopathies, pericardial disease, stroke, peripheral vascular disease, and venous thromboembolism. For participants with cardiovascular magnetic resonance (CMR) available as part of the UK Biobank Imaging Study, we considered measures of cardiac structure and function extracted using automated pipelines. Associations of RA with prevalent and incident CVDs were calculated using logistic and Cox regression. Linear regression was used to examine associations with CMR metrics. Models were adjusted for demographic, lifestyle, and clinical confounders. Causal associations were assessed using two-sample Mendelian randomisation. Genetic instruments for RA (22,350 cases and 74,823 controls), nine CVDs (FinnGen, n = 224,737), and 11 CMR phenotypes (UK Biobank) were extracted and associations assessed using inverse-variance weighting with pleiotropy adjustments and multiple testing corrections. 

Results: the analysis included 1,436 RA cases (mean age 59.9 years; 70.6% female) and 476,975 controls (mean age 56.5 years; 54.3% female). Participants with RA lived in more socioeconomically deprived areas (as per the Townsend Deprivation Index), had lower physical activity levels, were more likely to smoke, and had a higher baseline prevalence of CVDs. In fully adjusted models, participants with RA had a significantly higher hazard of multiple incident CVDs, with the greatest risks related to pericardial disease (HR 2.63 (1.85, 3.74)), heart failure (HR 1.68 (1.42, 1.99)), and AMI (HR 1.53 (1.20, 1.96)). Mendelian Randomisation analyses supported causal links between RA and AMI (OR 1.07 (1.02, 1.09), p = 0.009), arrhythmias (OR 1.05 (1.02, 1.06), p = 0.0007), and IHD (OR 1.05 (1.01, 1.06), p = 0.036). No significant associations were identified between RA and CMR phenotypes. 

Conclusions: people with RA have a heightened risk of multiple prevalent and incident CVDs, independent of shared risk factors, with suggestions of causal links with IHD, AMI, and arrhythmias.

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s12916-025-04431-1 - Version of Record
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Accepted/In Press date: 6 October 2025
Published date: 3 November 2025
Keywords: Cardiovascular disease, Causal association, Epidemiology, Ischaemic heart disease, Mendelian randomisation, Pericardial disease, Rheumatoid arthritis, Risk factors, UK Biobank

Identifiers

Local EPrints ID: 506797
URI: http://eprints.soton.ac.uk/id/eprint/506797
ISSN: 1741-7015
PURE UUID: 7650ff17-0296-4e13-a1f5-b1217f39f668
ORCID for Stefania D'angelo: ORCID iD orcid.org/0000-0002-7267-1837
ORCID for Elizabeth Curtis: ORCID iD orcid.org/0000-0002-5147-0550
ORCID for Nicholas C. Harvey: ORCID iD orcid.org/0000-0002-8194-2512

Catalogue record

Date deposited: 18 Nov 2025 17:56
Last modified: 19 Nov 2025 02:51

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Contributors

Author: Janek Salaztzi
Author: Dorina-Gabriela Condurache
Author: Stefania D'angelo ORCID iD
Author: Ahmed M. Salih
Author: Liliana Szabo
Author: Adil Mahmood
Author: Steffen E. Petersen
Author: Andre Altmann
Author: Norbert Frey
Author: Florian Andre
Author: Zahra Raisi-Estabragh

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