{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:56:55Z","timestamp":1789624615742,"version":"build-2803163510"},"reference-count":65,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Deutsche Zentrum f\u00fcr Herz-Kreislauf-Forschung e.V. (DZHK), Germany"},{"name":"Deutsche Herzstiftung e.V., Germany"},{"name":"National Institute for Health and Care Research Barts Biomedical Research Centre","award":["NIHR203330"],"award-info":[{"award-number":["NIHR203330"]}]},{"DOI":"10.13039\/100015652","name":"Barts Charity","doi-asserted-by":"publisher","award":["G-002530, G-002777"],"award-info":[{"award-number":["G-002530, G-002777"]}],"id":[{"id":"10.13039\/100015652","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015652","name":"Barts Charity","doi-asserted-by":"publisher","award":["G-002389"],"award-info":[{"award-number":["G-002389"]}],"id":[{"id":"10.13039\/100015652","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MC_PC_21003; MC_PC_21001"],"award-info":[{"award-number":["MC_PC_21003; MC_PC_21001"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100022419","name":"National Institute for Health Research Southampton Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100022419","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Leicester City Football Club (LCFC) Programme"},{"name":"National Institute for Healthcare Research (NIHR) Integrated Academic Training","award":["ACF-2022-19-003"],"award-info":[{"award-number":["ACF-2022-19-003"]}]},{"name":"NIHR Integrated Academic Training programme","award":["CL-2021-19-00"],"award-info":[{"award-number":["CL-2021-19-00"]}]},{"name":"British Heart Foundation Clinical Research Training Fellowship","award":["FS\/17\/81\/33318"],"award-info":[{"award-number":["FS\/17\/81\/33318"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>This study evaluated observational and causal relationships between rheumatoid arthritis (RA) and cardiovascular disease and imaging phenotypes in the UK Biobank.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      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\u00a0years 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                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009224,737), and 11 CMR phenotypes (UK Biobank) were extracted and associations assessed using inverse-variance weighting with pleiotropy adjustments and multiple testing corrections.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The analysis included 1,436 RA cases (mean age 59.9\u00a0years; 70.6% female) and 476,975 controls (mean age 56.5\u00a0years; 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),\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.009), arrhythmias (OR 1.05 (1.02, 1.06),\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0007), and IHD (OR 1.05 (1.01, 1.06),\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.036). No significant associations were identified between RA and CMR phenotypes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12916-025-04431-1","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T11:03:40Z","timestamp":1762167820000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Rheumatoid arthritis and cardiovascular disease associations in the UK Biobank"],"prefix":"10.1186","volume":"23","author":[{"given":"Janek","family":"Salatzki","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorina-Gabriela","family":"Condurache","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"D\u2019Angelo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed M.","family":"Salih","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana","family":"Szabo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adil","family":"Mahmood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth M.","family":"Curtis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen E.","family":"Petersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Altmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Frey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Andr\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas C.","family":"Harvey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahra","family":"Raisi-Estabragh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,3]]},"reference":[{"key":"4431_CR1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9062008","author":"J-W Kim","year":"2020","unstructured":"Kim J-W, Suh C-H. Systemic manifestations and complications in patients with rheumatoid arthritis. J Clin Med. 2020. https:\/\/doi.org\/10.3390\/jcm9062008.","journal-title":"J Clin Med"},{"key":"4431_CR2","doi-asserted-by":"publisher","first-page":"2023","DOI":"10.1016\/S0140-6736(16)30173-8","volume":"388","author":"JS Smolen","year":"2016","unstructured":"Smolen JS, Aletaha D, McInnes IB. Rheumatoid arthritis. Lancet. 2016;388:2023\u201338.","journal-title":"Lancet"},{"key":"4431_CR3","doi-asserted-by":"publisher","first-page":"1690","DOI":"10.1002\/art.24092","volume":"59","author":"JA Avi\u00f1a-Zubieta","year":"2008","unstructured":"Avi\u00f1a-Zubieta JA, Choi HK, Sadatsafavi M, Etminan M, Esdaile JM, Lacaille D. Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies. Arthritis Rheum. 2008;59:1690\u20137.","journal-title":"Arthritis Rheum"},{"key":"4431_CR4","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1136\/annrheumdis-2017-211735","volume":"77","author":"CS Crowson","year":"2018","unstructured":"Crowson CS, Rollefstad S, Ikdahl E, Kitas GD, van Riel PLCM, Gabriel SE, et al. Impact of risk factors associated with cardiovascular outcomes in patients with rheumatoid arthritis. Ann Rheum Dis. 2018;77:48\u201354.","journal-title":"Ann Rheum Dis"},{"key":"4431_CR5","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1136\/annrheumdis-2014-206624","volume":"74","author":"C Roubille","year":"2015","unstructured":"Roubille C, Richer V, Starnino T, McCourt C, McFarlane A, Fleming P, et al. The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal anti-inflammatory drugs and corticosteroids on cardiovascular events in rheumatoid arthritis, psoriasis and psoriatic arthritis: a systematic review and meta-analysis. Ann Rheum Dis. 2015;74:480\u20139.","journal-title":"Ann Rheum Dis"},{"key":"4431_CR6","doi-asserted-by":"publisher","DOI":"10.3390\/cells10040881","author":"J Chen","year":"2021","unstructured":"Chen J, Norling LV, Cooper D. Cardiac dysfunction in rheumatoid arthritis: the role of inflammation. Cells. 2021. https:\/\/doi.org\/10.3390\/cells10040881.","journal-title":"Cells"},{"key":"4431_CR7","doi-asserted-by":"publisher","first-page":"1287","DOI":"10.1007\/s10067-024-06878-8","volume":"43","author":"B Wang","year":"2024","unstructured":"Wang B, Liu J, Zhao L. Association of congestive heart failure with mortality in individuals with rheumatoid arthritis: a cohort study. Clin Rheumatol. 2024;43:1287\u201397.","journal-title":"Clin Rheumatol"},{"key":"4431_CR8","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1136\/annrheumdis-2014-206411","volume":"75","author":"E Myasoedova","year":"2016","unstructured":"Myasoedova E, Chandran A, Ilhan B, Major BT, Michet CJ, Matteson EL, et al. The role of rheumatoid arthritis (RA) flare and cumulative burden of RA severity in the risk of cardiovascular disease. Ann Rheum Dis. 2016;75:560\u20135.","journal-title":"Ann Rheum Dis"},{"key":"4431_CR9","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/809514","volume":"2015","author":"AK Bacani","year":"2015","unstructured":"Bacani AK, Crowson CS, Roger VL, Gabriel SE, Matteson EL. Increased incidence of atrial fibrillation in patients with rheumatoid arthritis. Biomed Res Int. 2015;2015:809514.","journal-title":"Biomed Res Int"},{"key":"4431_CR10","doi-asserted-by":"publisher","DOI":"10.1111\/eci.12915","volume":"48","author":"BB L\u00f8gstrup","year":"2018","unstructured":"L\u00f8gstrup BB, Ellingsen T, Pedersen AB, Kjaersgaard A, B\u00f8tker H-E, Maeng M. Development of heart failure in patients with rheumatoid arthritis: A Danish population-based study. Eur J Clin Invest. 2018;48:e12915.","journal-title":"Eur J Clin Invest"},{"key":"4431_CR11","first-page":"1368","volume":"42","author":"JA Federico","year":"2024","unstructured":"Federico JA, Syv\u00e4ranta SA, Tuohinen SS, Holmstr\u00f6m MM, Peltomaa RL, Koivuniemi RP, et al. Myocardial T1 mapping by cardiac magnetic resonance imaging shows early myocardial changes in treatment-naive patients with active rheumatoid arthritis and positive autoantibodies. Clin Exp Rheumatol. 2024;42:1368\u201376.","journal-title":"Clin Exp Rheumatol"},{"key":"4431_CR12","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1016\/j.jcmg.2014.12.025","volume":"8","author":"NAB Ntusi","year":"2015","unstructured":"Ntusi NAB, Piechnik SK, Francis JM, Ferreira VM, Matthews PM, Robson MD, et al. Diffuse Myocardial Fibrosis and Inflammation in Rheumatoid Arthritis: Insights From CMR T1 Mapping. JACC Cardiovasc Imaging. 2015;8:526\u201336.","journal-title":"JACC Cardiovasc Imaging"},{"key":"4431_CR13","doi-asserted-by":"publisher","first-page":"4639","DOI":"10.1007\/s00330-017-4838-4","volume":"27","author":"S Greulich","year":"2017","unstructured":"Greulich S, Mayr A, Kitterer D, Latus J, Henes J, Vecchio F, et al. Advanced myocardial tissue characterisation by a multi-component CMR protocol in patients with rheumatoid arthritis. Eur Radiol. 2017;27:4639\u201349.","journal-title":"Eur Radiol"},{"key":"4431_CR14","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1002\/sim.3034","volume":"27","author":"DA Lawlor","year":"2008","unstructured":"Lawlor DA, Harbord RM, Sterne JAC, Timpson N, Davey SG. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med. 2008;27:1133\u201363.","journal-title":"Stat Med"},{"key":"4431_CR15","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2023.1033644","volume":"10","author":"Q Nie","year":"2023","unstructured":"Nie Q, Luo Q, Yan W, Zhang T, Wang H, Wu J. Rheumatoid arthritis and coronary atherosclerosis: a two-sample Mendelian randomization study. Front Cardiovasc Med. 2023;10:1033644.","journal-title":"Front Cardiovasc Med"},{"key":"4431_CR16","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2023.1099861","volume":"10","author":"M Wang","year":"2023","unstructured":"Wang M, Chao C, Mei K, Di D, Qian Y, Wang B, et al. Relationship between rheumatoid arthritis and cardiovascular comorbidity, causation or co-occurrence: a Mendelian randomization study. Front Cardiovasc Med. 2023;10:1099861.","journal-title":"Front Cardiovasc Med"},{"key":"4431_CR17","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1154271","volume":"14","author":"M Wang","year":"2023","unstructured":"Wang M, Mei K, Chao C, Di D, Qian Y, Wang B, et al. Rheumatoid arthritis increases the risk of heart failure-current evidence from genome-wide association studies. Front Endocrinol (Lausanne). 2023;14:1154271.","journal-title":"Front Endocrinol (Lausanne)"},{"key":"4431_CR18","doi-asserted-by":"publisher","DOI":"10.5334\/gh.1256","volume":"18","author":"X Lin","year":"2023","unstructured":"Lin X, Zhou M, Zhang C, Li J. Genetically determined rheumatoid arthritis may not affect heart failure: insights from Mendelian randomization study. Glob Heart. 2023;18:43.","journal-title":"Glob Heart"},{"key":"4431_CR19","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1007\/s10067-023-06804-4","volume":"43","author":"J-C Rong","year":"2024","unstructured":"Rong J-C, Chen X-D, Jin N-K, Hong J. Exploring the causal association of rheumatoid arthritis with atrial fibrillation: a Mendelian randomization study. Clin Rheumatol. 2024;43:29\u201340.","journal-title":"Clin Rheumatol"},{"key":"4431_CR20","doi-asserted-by":"crossref","unstructured":"Song Q, Shang L, Zhang Y, Cui Y, Du J, Yinglong H. Rheumatoid Arthritis and Risk of Atrial Fibrillation: Results from Pooled Cohort Studies and Mendelian Randomization Analysis. Cardiovascular Innovations and Applications. 2024;9.","DOI":"10.15212\/CVIA.2024.0006"},{"key":"4431_CR21","doi-asserted-by":"publisher","first-page":"1638","DOI":"10.1002\/art.42239","volume":"74","author":"S Yuan","year":"2022","unstructured":"Yuan S, Carter P, Mason AM, Yang F, Burgess S, Larsson SC. Genetic liability to rheumatoid arthritis in relation to coronary artery disease and stroke risk. Arthritis Rheumatol. 2022;74:1638\u201347.","journal-title":"Arthritis Rheumatol"},{"key":"4431_CR22","unstructured":"UK Biobank Coordinating Centre UK Biobank: Protocol for a large-scale prospective epidemiological resource."},{"key":"4431_CR23","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1093\/ehjci\/jeaa297","volume":"22","author":"Z Raisi-Estabragh","year":"2021","unstructured":"Raisi-Estabragh Z, Harvey NC, Neubauer S, Petersen SE. Cardiovascular magnetic resonance imaging in the UK Biobank: a major international health research resource. Eur Heart J Cardiovasc Imaging. 2021;22:251\u20138.","journal-title":"Eur Heart J Cardiovasc Imaging"},{"key":"4431_CR24","doi-asserted-by":"publisher","DOI":"10.1136\/rmdopen-2016-000267","volume":"2","author":"S Siebert","year":"2016","unstructured":"Siebert S, Lyall DM, Mackay DF, Porter D, McInnes IB, Sattar N, et al. Characteristics of rheumatoid arthritis and its association with major comorbid conditions: cross-sectional study of 502 649 UK Biobank participants. RMD Open. 2016;2:e000267.","journal-title":"RMD Open"},{"key":"4431_CR25","doi-asserted-by":"publisher","DOI":"10.1186\/s12968-016-0227-4","volume":"18","author":"SE Petersen","year":"2016","unstructured":"Petersen SE, Matthews PM, Francis JM, Robson MD, Zemrak F, Boubertakh R, et al. UK Biobank\u2019s cardiovascular magnetic resonance protocol. J Cardiovasc Magn Reson. 2016;18:8.","journal-title":"J Cardiovasc Magn Reson"},{"key":"4431_CR26","doi-asserted-by":"publisher","first-page":"1654","DOI":"10.1038\/s41591-020-1009-y","volume":"26","author":"W Bai","year":"2020","unstructured":"Bai W, Suzuki H, Huang J, Francis C, Wang S, Tarroni G, et al. A population-based phenome-wide association study of cardiac and aortic structure and function. Nat Med. 2020;26:1654\u201362.","journal-title":"Nat Med"},{"key":"4431_CR27","doi-asserted-by":"publisher","first-page":"1640","DOI":"10.1038\/s41588-022-01213-w","volume":"54","author":"K Ishigaki","year":"2022","unstructured":"Ishigaki K, Sakaue S, Terao C, Luo Y, Sonehara K, Yamaguchi K, et al. Multi-ancestry genome-wide association analyses identify novel genetic mechanisms in rheumatoid arthritis. Nat Genet. 2022;54:1640\u201351.","journal-title":"Nat Genet"},{"key":"4431_CR28","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1002\/art.1780310302","volume":"31","author":"FC Arnett","year":"1988","unstructured":"Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988;31:315\u201324.","journal-title":"Arthritis Rheum"},{"key":"4431_CR29","doi-asserted-by":"publisher","first-page":"2569","DOI":"10.1002\/art.27584","volume":"62","author":"D Aletaha","year":"2010","unstructured":"Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology\/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62:2569\u201381.","journal-title":"Arthritis Rheum"},{"key":"4431_CR30","unstructured":"Kurki MI, Karjalainen J, Palta P, Sipil\u00e4 TP, Kristiansson K, Donner K, et al. FinnGen: Unique genetic insights from combining isolated population and national health register data. medRxiv. 2022;:2022.03.03.22271360."},{"key":"4431_CR31","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1038\/s41588-022-01083-2","volume":"54","author":"N Aung","year":"2022","unstructured":"Aung N, Vargas JD, Yang C, Fung K, Sanghvi MM, Piechnik SK, et al. Genome-wide association analysis reveals insights into the genetic architecture of right ventricular structure and function. Nat Genet. 2022;54:783\u201391.","journal-title":"Nat Genet"},{"key":"4431_CR32","doi-asserted-by":"publisher","first-page":"1318","DOI":"10.1161\/CIRCULATIONAHA.119.041161","volume":"140","author":"N Aung","year":"2019","unstructured":"Aung N, Vargas JD, Yang C, Cabrera CP, Warren HR, Fung K, et al. Genome-wide analysis of left ventricular image-derived phenotypes identifies fourteen loci associated with cardiac morphogenesis and heart failure development. Circulation. 2019;140:1318\u201330.","journal-title":"Circulation"},{"key":"4431_CR33","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1038\/s41588-022-01090-3","volume":"54","author":"JP Pirruccello","year":"2022","unstructured":"Pirruccello JP, Di Achille P, Nauffal V, Nekoui M, Friedman SF, Klarqvist MDR, et al. Genetic analysis of right heart structure and function in 40,000 people. Nat Genet. 2022;54:792\u2013803.","journal-title":"Nat Genet"},{"key":"4431_CR34","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1038\/s41588-023-01371-5","volume":"55","author":"V Nauffal","year":"2023","unstructured":"Nauffal V, Di Achille P, Klarqvist MDR, Cunningham JW, Hill MC, Pirruccello JP, et al. Genetics of myocardial interstitial fibrosis in the human heart and association with disease. Nat Genet. 2023;55:777\u201386.","journal-title":"Nat Genet"},{"issue":"1","key":"4431_CR35","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-45703-0","volume":"9","author":"K Fung","year":"2019","unstructured":"Fung K, Ram\u00edrez J, Warren HR, Aung N, Lee AM, Tzanis E, et al. Genome-wide association study identifies loci for arterial stiffness index in 127,121 UK Biobank participants. Sci Rep. 2019;9(1):9143.","journal-title":"Sci Rep"},{"key":"4431_CR36","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32219-x","volume":"13","author":"CM Francis","year":"2022","unstructured":"Francis CM, Futschik ME, Huang J, Bai W, Sargurupremraj M, Teumer A, et al. Genome-wide associations of aortic distensibility suggest causality for aortic aneurysms and brain white matter hyperintensities. Nat Commun. 2022;13:4505.","journal-title":"Nat Commun"},{"key":"4431_CR37","unstructured":"Hemani G, Elsworth B, Palmer T, Rasteiro R. ieugwasr: Interface to the \u201cOpenGWAS\u201d Database API."},{"key":"4431_CR38","unstructured":"National Bioscience Database Center (NBDC), Japan Science and Technology Agency (JST). PheWeb Japan. https:\/\/pheweb.jp. Accessed 29 Jun 2025."},{"key":"4431_CR39","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1207\/s15327906mbr3304_5","volume":"33","author":"JL Schafer","year":"1998","unstructured":"Schafer JL, Olsen MK. Multiple imputation for multivariate missing-data problems: a data analyst\u2019s perspective. Multivariate Behav Res. 1998;33:545\u201371.","journal-title":"Multivariate Behav Res"},{"key":"4431_CR40","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1002\/gepi.21965","volume":"40","author":"J Bowden","year":"2016","unstructured":"Bowden J, Davey Smith G, Haycock PC, Burgess S. Consistent estimation in Mendelian randomization with some invalid instruments using a weighted median estimator. Genet Epidemiol. 2016;40:304\u201314.","journal-title":"Genet Epidemiol"},{"key":"4431_CR41","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1038\/s41588-018-0099-7","volume":"50","author":"M Verbanck","year":"2018","unstructured":"Verbanck M, Chen C-Y, Neale B, Do R. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat Genet. 2018;50:693\u20138.","journal-title":"Nat Genet"},{"key":"4431_CR42","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1002\/gepi.22284","volume":"44","author":"L Deng","year":"2020","unstructured":"Deng L, Zhang H, Yu K. Power calculation for the general two-sample Mendelian randomization analysis. Genet Epidemiol. 2020;44:290\u20139.","journal-title":"Genet Epidemiol"},{"key":"4431_CR43","doi-asserted-by":"publisher","first-page":"1642","DOI":"10.1136\/annrheumdis-2016-211066","volume":"76","author":"M Holmqvist","year":"2017","unstructured":"Holmqvist M, Ljung L, Askling J. Acute coronary syndrome in new-onset rheumatoid arthritis: a population-based nationwide cohort study of time trends in risks and excess risks. Ann Rheum Dis. 2017;76:1642\u20137.","journal-title":"Ann Rheum Dis"},{"key":"4431_CR44","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1002\/art.20853","volume":"52","author":"H Maradit-Kremers","year":"2005","unstructured":"Maradit-Kremers H, Crowson CS, Nicola PJ, Ballman KV, Roger VL, Jacobsen SJ, et al. Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis: a population-based cohort study. Arthritis Rheum. 2005;52:402\u201311.","journal-title":"Arthritis Rheum"},{"key":"4431_CR45","doi-asserted-by":"publisher","first-page":"1440","DOI":"10.1038\/s41591-024-02905-y","volume":"30","author":"J Hippisley-Cox","year":"2024","unstructured":"Hippisley-Cox J, Coupland CAC, Bafadhel M, Russell REK, Sheikh A, Brindle P, et al. Development and validation of a new algorithm for improved cardiovascular risk prediction. Nat Med. 2024;30:1440\u20137.","journal-title":"Nat Med"},{"key":"4431_CR46","doi-asserted-by":"publisher","first-page":"3415","DOI":"10.1093\/eurheartj\/ehae177","volume":"45","author":"C Vrints","year":"2024","unstructured":"Vrints C, Andreotti F, Koskinas KC, Rossello X, Adamo M, Ainslie J, et al. 2024 ESC guidelines for the management of chronic coronary syndromes. Eur Heart J. 2024;45:3415\u2013537.","journal-title":"Eur Heart J"},{"key":"4431_CR47","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1002\/acr.20371","volume":"63","author":"C Barnabe","year":"2011","unstructured":"Barnabe C, Martin B-J, Ghali WA. Systematic review and meta-analysis: anti-tumor necrosis factor \u03b1 therapy and cardiovascular events in rheumatoid arthritis. Arthritis Care Res (Hoboken). 2011;63:522\u20139.","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"4431_CR48","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1093\/rheumatology\/keq316","volume":"50","author":"SL Westlake","year":"2011","unstructured":"Westlake SL, Colebatch AN, Baird J, Curzen N, Kiely P, Quinn M, et al. Tumour necrosis factor antagonists and the risk of cardiovascular disease in patients with rheumatoid arthritis: a systematic literature review. Rheumatology (Oxford). 2011;50:518\u201331.","journal-title":"Rheumatology (Oxford)"},{"key":"4431_CR49","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1002\/art.38894","volume":"67","author":"A Souto","year":"2015","unstructured":"Souto A, Salgado E, Maneiro JR, Mera A, Carmona L, G\u00f3mez-Reino JJ. Lipid profile changes in patients with chronic inflammatory arthritis treated with biologic agents and tofacitinib in randomized clinical trials: a systematic review and meta-analysis. Arthritis Rheumatol. 2015;67:117\u201327.","journal-title":"Arthritis Rheumatol"},{"key":"4431_CR50","doi-asserted-by":"publisher","first-page":"2031","DOI":"10.1016\/j.ijcard.2012.05.057","volume":"167","author":"S Corrao","year":"2013","unstructured":"Corrao S, Messina S, Pistone G, Calvo L, Scaglione R, Licata G. Heart involvement in rheumatoid arthritis: systematic review and meta-analysis. Int J Cardiol. 2013;167:2031\u20138.","journal-title":"Int J Cardiol"},{"key":"4431_CR51","volume":"2012","author":"MB Owlia","year":"2012","unstructured":"Owlia MB, Mostafavi Pour Manshadi SMY, Naderi N. Cardiac manifestations of rheumatological conditions: a narrative review. ISRN Rheumatol. 2012;2012:463620.","journal-title":"ISRN Rheumatol"},{"key":"4431_CR52","doi-asserted-by":"publisher","DOI":"10.1007\/s11886-020-01415-w","volume":"22","author":"A Kontzias","year":"2020","unstructured":"Kontzias A, Barkhodari A, Yao Q. Pericarditis in systemic rheumatologic diseases. Curr Cardiol Rep. 2020;22:142.","journal-title":"Curr Cardiol Rep"},{"key":"4431_CR53","first-page":"1717","volume":"38","author":"PE Lazzerini","year":"2017","unstructured":"Lazzerini PE, Capecchi PL, Laghi-Pasini F. Systemic inflammation and arrhythmic risk: lessons from rheumatoid arthritis. Eur Heart J. 2017;38:1717\u201327.","journal-title":"Eur Heart J"},{"key":"4431_CR54","doi-asserted-by":"publisher","DOI":"10.1155\/2024\/3274074","volume":"2024","author":"W Luo","year":"2024","unstructured":"Luo W, Yv H, Yu X, Wu X. Investigating the causal link between Rheumatoid arthritis and Atrial fibrillation in East Asian populations: a Mendelian randomization approach. Cardiol Res Pract. 2024;2024:3274074.","journal-title":"Cardiol Res Pract"},{"key":"4431_CR55","doi-asserted-by":"publisher","unstructured":"Kanai M, Ulirsch JC, Karjalainen J, Kurki M, Karczewski KJ, Fauman E, et al. Insights from complex trait fine-mapping across diverse populations. medRxiv. 2021. https:\/\/doi.org\/10.1101\/2021.09.03.21262975.","DOI":"10.1101\/2021.09.03.21262975"},{"key":"4431_CR56","doi-asserted-by":"publisher","first-page":"1286","DOI":"10.1093\/rheumatology\/ken159","volume":"47","author":"VF Panoulas","year":"2008","unstructured":"Panoulas VF, Metsios GS, Pace AV, John H, Treharne GJ, Banks MJ, et al. Hypertension in rheumatoid arthritis. Rheumatology (Oxford). 2008;47:1286\u201398.","journal-title":"Rheumatology (Oxford)"},{"key":"4431_CR57","doi-asserted-by":"crossref","unstructured":"Hadwen B, Stranges S, Pope JE, Bartlett S, Boire G, Bessette L, et al. Risk factors for prevalent and incident hypertension in rheumatoid arthritis: data from the Canadian Early Arthritis Cohort. Rheumatol Adv Pract. 2024;8:rkae066.","DOI":"10.1093\/rap\/rkae066"},{"key":"4431_CR58","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1097\/XCE.0000000000000244","volume":"10","author":"Z Tian","year":"2021","unstructured":"Tian Z, Mclaughlin J, Verma A, Chinoy H, Heald AH. The relationship between rheumatoid arthritis and diabetes mellitus: a systematic review and meta-analysis. Cardiovasc Endocrinol Metab. 2021;10:125\u201331.","journal-title":"Cardiovasc Endocrinol Metab"},{"key":"4431_CR59","doi-asserted-by":"publisher","first-page":"2239","DOI":"10.1016\/S0140-6736(17)30058-2","volume":"389","author":"S Chatterjee","year":"2017","unstructured":"Chatterjee S, Khunti K, Davies MJ. Type 2 diabetes. Lancet. 2017;389:2239\u201351.","journal-title":"Lancet"},{"key":"4431_CR60","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1002\/acr.23611","volume":"71","author":"JC Wilson","year":"2019","unstructured":"Wilson JC, Sarsour K, Gale S, Peth\u00f6-Schramm A, Jick SS, Meier CR. Incidence and Risk of Glucocorticoid-Associated Adverse Effects in Patients With Rheumatoid Arthritis. Arthritis Care Res (Hoboken). 2019;71:498\u2013511.","journal-title":"Arthritis Care Res (Hoboken)"},{"key":"4431_CR61","doi-asserted-by":"publisher","first-page":"3912","DOI":"10.1093\/eurheartj\/ehae178","volume":"45","author":"JW McEvoy","year":"2024","unstructured":"McEvoy JW, McCarthy CP, Bruno RM, Brouwers S, Canavan MD, Ceconi C, et al. 2024 ESC Guidelines for the management of elevated blood pressure and hypertension. Eur Heart J. 2024;45:3912\u20134018.","journal-title":"Eur Heart J"},{"key":"4431_CR62","doi-asserted-by":"publisher","first-page":"2921","DOI":"10.1093\/eurheartj\/ehv318","volume":"36","author":"Y Adler","year":"2015","unstructured":"Adler Y, Charron P, Imazio M, Badano L, Bar\u00f3n-Esquivias G, Bogaert J, et al. 2015 ESC Guidelines for the diagnosis and management of pericardial diseases: The Task Force for the Diagnosis and Management of Pericardial Diseases of the European Society of Cardiology (ESC)Endorsed by: The European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J. 2015;36:2921\u201364.","journal-title":"Eur Heart J"},{"key":"4431_CR63","unstructured":"UK Biobank Coordinating Centre. UK Biobank resource and access procedures. UK Biobank. https:\/\/www.ukbiobank.ac.uk\/use-our-data\/apply-for-access\/ (2007)"},{"key":"4431_CR64","unstructured":"FinnGen Consortium. FinnGen Data Freeze R10. Finnish Institute for Health and Welfare. https:\/\/www.finngen.fi\/en (2023)"},{"key":"4431_CR65","unstructured":"National Bioscience Database Center (NBDC), Japan Science and Technology Agency (JST). BioBank Japan PheWeb (East Asian GWAS summary statistics). https:\/\/pheweb.jp (2025)"}],"container-title":["BMC Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12916-025-04431-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12916-025-04431-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12916-025-04431-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T12:05:21Z","timestamp":1762171521000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcmedicine.biomedcentral.com\/articles\/10.1186\/s12916-025-04431-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,3]]},"references-count":65,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["4431"],"URL":"https:\/\/doi.org\/10.1186\/s12916-025-04431-1","relation":{},"ISSN":["1741-7015"],"issn-type":[{"value":"1741-7015","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,3]]},"assertion":[{"value":"28 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 November 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This study adheres to the Declaration of Helsinki and is covered by ethical approval for UK Biobank studies granted by the NHS National Research Ethics Service on June 17, 2011 (Ref 11\/NW\/0382), with an extension on June 18, 2021 (Ref 21\/NW\/0157). Written informed consent was obtained from all participants. Individuals who withdrew their consent after recruitment were excluded from the analysis. For the MR analyses, the study was conducted using publicly available GWAS summary statistics, and as such, ethical approval was not required.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"SEP provides consultancy to Cardiovascular Imaging Inc, Calgary, Alberta, Canada. All other authors declare no conflicts of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"605"}}