{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:18:57Z","timestamp":1787725137660,"version":"build-2784847793"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":37,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100004325","name":"AstraZeneca","doi-asserted-by":"publisher","award":["ESR-22-22019"],"award-info":[{"award-number":["ESR-22-22019"]}],"id":[{"id":"10.13039\/100004325","id-type":"DOI","asserted-by":"publisher"}]}],"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>Cardiovascular-kidney-metabolic (CKM) disease and chronic obstructive pulmonary disease (COPD) are associated with major adverse cardiovascular events (MACE). Whether COPD further increases MACE risk within CKM populations, and whether this potential risk is modifiable through inhaled corticosteroids (ICS), is unknown. Within CKM populations, we investigated the relationship between (1) COPD and subsequent MACE, and (2) amongst concurrent CKM-COPD populations, we investigated the relationship between ICS and subsequent MACE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used Clinical Practice Research Datalink (CPRD) Aurum, Hospital Episode Statistics and Office of National Statistics data, between January 1st, 2010, and March 29th, 2021. We created five discrete cohorts: chronic kidney disease (CKD), type-II diabetes mellitus (T2DM), obesity, MACE history, and older adults (aged\u2009\u2265\u200965\u00a0years old [\u201cAge65\u2009+\u2009\u201d]). CKD, T2DM, obesity, and Age65\u2009+\u2009cohorts were MACE-na\u00efve at the time of inclusion. Aim (1) exposures were (a) COPD, (b) incident COPD, and (c) being at risk of COPD without diagnosis (defined as age\u2009\u2265\u200940\u00a0years old, smoking history, no evidence of asthma, and frequent respiratory infections requiring antibiotics). Aim (2) exposure was ICS prescription (control group: long-acting bronchodilators). The outcome was MACE (acute coronary syndrome, arrhythmia, heart failure, ischaemic stroke, or cardiovascular-specific mortality). We implemented Cox proportional hazards models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      COPD was associated with MACE amongst all cohorts, but was comparatively weak in the MACE history cohort (cohort total; adjusted hazard ratio [95% confidence interval]): CKD (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u2009573,626; 1.29 [1.26, 1.32]), T2DM (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u2009649,506; 1.30 [1.26, 1.35], obesity (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u2009225,273; 1.41 [1.34, 1.48]), MACE history (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u2009507,889; 1.04 [1.02, 1.06]), and Age65\u2009+\u2009(\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u2009592,123, 1.59 [1.52, 1.66]). Incident COPD was associated with subsequent MACE in CKD only (1.28 [1.13, 1.45]). Being at risk of COPD was associated with subsequent MACE in CKD (1.18 [1.07, 1.30]), MACE history (1.16 [1.08, 1.25]), and Age65\u2009+\u2009(1.28 [1.13, 1.46]). ICS prescription was not associated with subsequent MACE in any concurrent CKM-COPD cohort.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>COPD was an independent risk factor for MACE in CKM populations. ICS did not attenuate MACE amongst CKM-COPD groups. Incident COPD was associated with MACE in CKD, and being at risk of COPD was associated with MACE in CKD, MACE history, and Age65\u2009+\u2009cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12916-026-04754-7","type":"journal-article","created":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T23:34:39Z","timestamp":1772580879000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The role of COPD and inhaled corticosteroids in major adverse cardiovascular events in cardiovascular-kidney-metabolic populations"],"prefix":"10.1186","volume":"24","author":[{"given":"Anne E.","family":"Ioannides","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily L.","family":"Graul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantinos","family":"Kallis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Upasana","family":"Tayal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hana","family":"M\u00fcllerov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer K.","family":"Quint","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,4]]},"reference":[{"key":"4754_CR1","doi-asserted-by":"publisher","first-page":"2283","DOI":"10.1111\/dom.14829","volume":"24","author":"T Kadowaki","year":"2022","unstructured":"Kadowaki T, Maegawa H, Watada H, Yabe D, Node K, Murohara T, et al. Interconnection between cardiovascular, renal and metabolic disorders: a narrative review with a focus on Japan. Obes Metab. 2022;24:2283\u201396.","journal-title":"Obes Metab"},{"key":"4754_CR2","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1007\/s00125-022-05857-5","volume":"66","author":"A Rosengren","year":"2023","unstructured":"Rosengren A, Dikaiou P. Cardiovascular outcomes in type 1 and type 2 diabetes. Diabetologia. 2023;66:425\u201337.","journal-title":"Diabetologia"},{"key":"4754_CR3","doi-asserted-by":"publisher","first-page":"e029083","DOI":"10.1161\/JAHA.122.029083","volume":"12","author":"M Fang","year":"2023","unstructured":"Fang M, Wang D, Tang O, McEvoy JW, Echouffo-Tcheugui JB, Christenson RH, et al. Subclinical cardiovascular disease in US adults with and without diabetes. JAHA. 2023;12:e029083.","journal-title":"JAHA"},{"key":"4754_CR4","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1038\/s41581-022-00616-6","volume":"18","author":"K Matsushita","year":"2022","unstructured":"Matsushita K, Ballew SH, Wang AY, Kalyesubula R, Schaeffner E, Agarwal R. Epidemiology and risk of cardiovascular disease in populations with chronic kidney disease. Nat Rev Nephrol. 2022;18:696\u2013707.","journal-title":"Nat Rev Nephrol"},{"key":"4754_CR5","doi-asserted-by":"publisher","first-page":"4019","DOI":"10.1093\/eurheartj\/ehae466","volume":"45","author":"A Timmis","year":"2024","unstructured":"Timmis A, Aboyans V, Vardas P, Townsend N, Torbica A, Kavousi M, et al. European Society of Cardiology: the 2023 atlas of cardiovascular disease statistics. EHJ. 2024;45:4019\u201362.","journal-title":"EHJ"},{"key":"4754_CR6","doi-asserted-by":"publisher","first-page":"2202364","DOI":"10.1183\/13993003.02364-2022","volume":"62","author":"LC Maclagan","year":"2023","unstructured":"Maclagan LC, Croxford R, Chu A, Sin DD, Udell JA, Lee DS, et al. Quantifying COPD as a risk factor for cardiac disease in a primary prevention cohort. Eur Respir J. 2023;62:2202364.","journal-title":"Eur Respir J"},{"key":"4754_CR7","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1111\/resp.14799","volume":"29","author":"K Cobb","year":"2024","unstructured":"Cobb K, Kenyon J, Lu J, Krieger B, Perelas A, Nana\u2010Sinkam P, et al. COPD is associated with increased cardiovascular disease risk independent of phenotype. Respirology. 2024;29:1047\u201357.","journal-title":"Respirology"},{"key":"4754_CR8","volume":"14","author":"N Madouros","year":"2022","unstructured":"Madouros N, Jarvis S, Saleem A, Koumadoraki E, Sharif S, Khan S. Is there an association between chronic obstructive pulmonary disease and chronic renal failure? Cureus. 2022;14:e26149.","journal-title":"Cureus"},{"key":"4754_CR9","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1007\/s40200-021-00766-7","volume":"20","author":"E Monsour","year":"2021","unstructured":"Monsour E, Rodriguez LM, Abdelmasih R, Tuna K, Abusaada K. Characteristics and outcomes of diabetic patients with acute exacerbation of COPD. J Diabetes Metab Disord. 2021;20:461\u20136.","journal-title":"J Diabetes Metab Disord"},{"key":"4754_CR10","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1093\/eurpub\/ckz219","volume":"30","author":"MT Casta\u00f1-Abad","year":"2020","unstructured":"Casta\u00f1-Abad MT, Montserrat-Capdevila J, Godoy P, Marsal JR, Ortega M, Alsed\u00e0 M, et al. Diabetes as a risk factor for severe exacerbation and death in patients with COPD: a prospective cohort study. Eur J Public Health. 2020;30:822\u20137.","journal-title":"Eur J Public Health"},{"key":"4754_CR11","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1136\/thx.2010.136077","volume":"65","author":"PM Calverley","year":"2010","unstructured":"Calverley PM, Anderson JA, Celli B, Ferguson GT, Jenkins C, Jones PW, et al. Cardiovascular events in patients with COPD: TORCH study results. Thorax. 2010;65:719\u201325.","journal-title":"Thorax"},{"key":"4754_CR12","doi-asserted-by":"publisher","first-page":"380","DOI":"10.7326\/0003-4819-149-6-200809160-00004","volume":"149","author":"TA Lee","year":"2008","unstructured":"Lee TA, Pickard AS, Au DH, Bartle B, Weiss KB. Risk for death associated with medications for recently diagnosed chronic obstructive pulmonary disease. Ann Intern Med. 2008;149:380\u201390.","journal-title":"Ann Intern Med"},{"key":"4754_CR13","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1378\/chest.130.3.640","volume":"130","author":"C Macie","year":"2006","unstructured":"Macie C, Wooldrage K, Manfreda J, Anthonisen NR. Inhaled corticosteroids and mortality in COPD. Chest. 2006;130:640\u20136.","journal-title":"Chest"},{"key":"4754_CR14","first-page":"317","volume":"10","author":"K Gadhvi","year":"2023","unstructured":"Gadhvi K, Kandeil M, Raveendran D, Choi J, Davies N, Nanchahal S, et al. Inhaled corticosteroids and risk of cardiovascular disease in chronic obstructive pulmonary disease: a systematic review and meta-regression. Chronic Obstr Pulm Dis. 2023;10:317\u201327.","journal-title":"Chronic Obstr Pulm Dis"},{"key":"4754_CR15","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/7097540","author":"X Jing","year":"2018","unstructured":"Jing X, Li Y, Xu J. Risk of cardiovascular events associated with inhaled corticosteroid treatment in patients with chronic obstructive pulmonary disease: a meta-analysis. Can Respir J. 2018. https:\/\/doi.org\/10.1155\/2018\/7097540.","journal-title":"Can Respir J"},{"key":"4754_CR16","doi-asserted-by":"publisher","first-page":"189","DOI":"10.2147\/COPD.S6942","volume":"5","author":"S Singh","year":"2010","unstructured":"Singh S, Loke YK. An overview of the benefits and drawbacks of inhaled corticosteroids in chronic obstructive pulmonary disease. Int J Chron Obstr Pulmon Dis. 2010;5:189\u201395.","journal-title":"Int J Chron Obstr Pulmon Dis"},{"key":"4754_CR17","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1136\/thorax-2024-222113","volume":"80","author":"AE Ioannides","year":"2025","unstructured":"Ioannides AE, Kallis C, Whittaker HR, Quint JK. Inhaled corticosteroids and major cardiovascular events in people with chronic obstructive pulmonary disease. Thorax. 2025;80:67\u201375.","journal-title":"Thorax"},{"key":"4754_CR18","doi-asserted-by":"publisher","unstructured":"Clinical Practice Research Datalink. 2023. CPRD Aurum December 2023 (Version 2023.12.001). Clinical Practice Research Datalink. https:\/\/doi.org\/10.48329\/7njs-8a57.","DOI":"10.48329\/7njs-8a57"},{"key":"4754_CR19","doi-asserted-by":"publisher","unstructured":"Clinical Practice Research Datalink. 2022. CPRD Aurum HES APC January 2022 (Version 2022.01.001). Clinical Practice Research Datalink. https:\/\/doi.org\/10.48329\/VAGX-9D96.","DOI":"10.48329\/VAGX-9D96"},{"key":"4754_CR20","doi-asserted-by":"publisher","unstructured":"Clinical Practice Research Datalink. 2022.\u00a0CPRD Aurum Small Area data (patient) January 2022\u00a0(Version 2022.01.001). Clinical Practice Research Datalink. https:\/\/doi.org\/10.48329\/AYTT-H222.","DOI":"10.48329\/AYTT-H222"},{"key":"4754_CR21","doi-asserted-by":"publisher","unstructured":"Clinical Practice Research Datalink. 2022.\u00a0CPRD Aurum ONS deaths January 2022\u00a0(Version 2022.01.001). Clinical Practice Research Datalink. https:\/\/doi.org\/10.48329\/Q34F-F505.","DOI":"10.48329\/Q34F-F505"},{"key":"4754_CR22","doi-asserted-by":"crossref","unstructured":"Wolf A, Dedman D, Campbell J, Booth H, Lunn D, Chapman J, et al. Data resource profile: Clinical Practice Research Datalink (CPRD) Aurum. Int J Epidemiol. 2019;48:1740-g","DOI":"10.1093\/ije\/dyz034"},{"key":"4754_CR23","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2014-005540","volume":"4","author":"JK Quint","year":"2014","unstructured":"Quint JK, M\u00fcllerova H, DiSantostefano RL, Forbes H, Eaton S, Hurst JR, et al. Validation of chronic obstructive pulmonary disease recording in the Clinical Practice Research Datalink (CPRD-GOLD). BMJ Open. 2014;4:e005540.","journal-title":"BMJ Open"},{"key":"4754_CR24","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.1136\/bmj.39609.449676.25","volume":"336","author":"J Hippisley-Cox","year":"2008","unstructured":"Hippisley-Cox J, Coupland C, Vinogradova Y, Robson J, Minhas R, Sheikh A, et al. Predicting cardiovascular risk in England and Wales: prospective derivation and validation of QRISK2. BMJ. 2008;336:1475\u201382.","journal-title":"BMJ"},{"key":"4754_CR25","unstructured":"Hippisley-Cox J. QRISK. 2021. GitHub repository: https:\/\/github.com\/emilyherrett\/qrisk_cprd_aurum."},{"key":"4754_CR26","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1186\/s12890-023-02606-1","volume":"23","author":"H Chen","year":"2023","unstructured":"Chen H, Luo X, Du Y, He C, Lu Y, Shi Z, et al. Association between chronic obstructive pulmonary disease and cardiovascular disease in adults aged 40 years and above: data from NHANES 2013\u20132018. BMC Pulm Med. 2023;23:318.","journal-title":"BMC Pulm Med"},{"key":"4754_CR27","first-page":"960","volume":"209","author":"EL Graul","year":"2024","unstructured":"Graul EL, Nordon C, Rhodes K, Marshall J, Menon S, Kallis C, et al. Temporal risk of nonfatal cardiovascular events after chronic obstructive pulmonary disease exacerbation: a population-based study. AJRCCM. 2024;209:960\u201372.","journal-title":"AJRCCM"},{"key":"4754_CR28","doi-asserted-by":"publisher","DOI":"10.3390\/life13061299","volume":"13","author":"A Papaporfyriou","year":"2023","unstructured":"Papaporfyriou A, Bartziokas K, Gompelmann D, Idzko M, Fouka E, Zaneli S, et al. Cardiovascular diseases in COPD: from diagnosis and prevalence to therapy. Life. 2023;13:1299.","journal-title":"Life"},{"key":"4754_CR29","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1016\/S2213-2600(23)00261-8","volume":"11","author":"LM Fabbri","year":"2023","unstructured":"Fabbri LM, Celli BR, Agust\u00ed A, Criner GJ, Dransfield MT, Divo M, et al. Copd and multimorbidity: recognising and addressing a syndemic occurrence. Lancet Respir Med. 2023;11:1020\u201334.","journal-title":"Lancet Respir Med"},{"key":"4754_CR30","doi-asserted-by":"publisher","DOI":"10.1038\/srep25855","volume":"6","author":"CY Chen","year":"2016","unstructured":"Chen CY, Liao KM. Chronic obstructive pulmonary disease is associated with risk of chronic kidney disease: a nationwide case-cohort study. Sci Rep. 2016;6:25855.","journal-title":"Sci Rep"},{"key":"4754_CR31","doi-asserted-by":"publisher","first-page":"2899","DOI":"10.2147\/COPD.S174215","volume":"13","author":"CC Lai","year":"2018","unstructured":"Lai CC, Wu CH, Wang YH, Wang CY, Wu VC, Chen L. The association between COPD and outcomes of patients with advanced chronic kidney disease. Int J Chron Obstr Pulmon Dis. 2018;13:2899\u2013905.","journal-title":"Int J Chron Obstr Pulmon Dis"},{"key":"4754_CR32","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1159\/000444422","volume":"43","author":"SD Navaneethan","year":"2016","unstructured":"Navaneethan SD, Schold JD, Huang H, Nakhoul G, Jolly SE, Arrigain S, et al. Mortality outcomes of patients with chronic kidney disease and chronic obstructive pulmonary disease. Am J Nephrol. 2016;43:39\u201346.","journal-title":"Am J Nephrol"},{"key":"4754_CR33","doi-asserted-by":"publisher","DOI":"10.1186\/s40001-024-01686-x","volume":"29","author":"Z Wang","year":"2024","unstructured":"Wang Z, Sun Y. Unraveling the causality between chronic obstructive pulmonary disease and its common comorbidities using bidirectional Mendelian randomization. Eur J Med Res. 2024;29:143.","journal-title":"Eur J Med Res"},{"key":"4754_CR34","doi-asserted-by":"publisher","first-page":"2575","DOI":"10.1111\/dom.15142","volume":"25","author":"J Su","year":"2023","unstructured":"Su J, Li M, Wan X, Yu H, Wan Y, Hang D, et al. Associations of diabetes, prediabetes and diabetes duration with the risk of chronic obstructive pulmonary disease: a prospective UK Biobank study. Diabetes Obes Metab. 2023;25:2575\u201385.","journal-title":"Diabetes Obes Metab"},{"key":"4754_CR35","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1159\/000369863","volume":"89","author":"S Gl\u00e4ser","year":"2015","unstructured":"Gl\u00e4ser S, Kr\u00fcger S, Merkel M, Bramlage P, Herth FJ. Chronic obstructive pulmonary disease and diabetes mellitus: a systematic review of the literature. Respiration. 2015;89:253\u201364.","journal-title":"Respiration"},{"key":"4754_CR36","doi-asserted-by":"publisher","first-page":"723","DOI":"10.2147\/COPD.S50111","volume":"9","author":"C Hanson","year":"2014","unstructured":"Hanson C, Rutten EP, Wouters EF, Rennard S. Influence of diet and obesity on COPD development and outcomes. Int J Chron Obstr Pulmon Dis. 2014;9:723\u201333.","journal-title":"Int J Chron Obstr Pulmon Dis"},{"key":"4754_CR37","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.chest.2016.08.1432","volume":"151","author":"AA Lambert","year":"2017","unstructured":"Lambert AA, Putcha N, Drummond MB, Boriek AM, Hanania NA, Kim V, et al. Obesity is associated with increased morbidity in moderate to severe COPD. Chest. 2017;151:68\u201377.","journal-title":"Chest"},{"key":"4754_CR38","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1136\/thorax-2023-220991","volume":"80","author":"EE Cho","year":"2025","unstructured":"Cho EE, Maclagan LC, Chu A, Croxford R, Sin DD, Udell JA, et al. Impact of COPD on cardiovascular risk factors and outcomes in people with established cardiovascular disease. Thorax. 2025;80:291\u20139.","journal-title":"Thorax"},{"key":"4754_CR39","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0193143","volume":"13","author":"MJ Divo","year":"2018","unstructured":"Divo MJ, Celli BR, Poblador-Plou B, Calder\u00f3n-Larra\u00f1aga A, de-Torres JP, Gimeno-Feliu LA, et al. Chronic obstructive pulmonary disease (COPD) as a disease of early aging: evidence from the EpiChron Cohort. PLoS ONE. 2018;13:e0193143.","journal-title":"PLoS ONE"},{"key":"4754_CR40","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 CA, Bafadhel M, Russell RE, 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":"4754_CR41","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1093\/eurheartj\/ehm516","volume":"29","author":"TC Clayton","year":"2008","unstructured":"Clayton TC, Thompson M, Meade TW. Recent respiratory infection and risk of cardiovascular disease: case-control study through a general practice database. EHJ. 2008;29:96\u2013103.","journal-title":"EHJ"},{"key":"4754_CR42","doi-asserted-by":"publisher","first-page":"2611","DOI":"10.1056\/NEJMoa041747","volume":"351","author":"L Smeeth","year":"2004","unstructured":"Smeeth L, Thomas SL, Hall AJ, Hubbard R, Farrington P, Vallance P. Risk of myocardial infarction and stroke after acute infection or vaccination. N Engl J Med. 2004;351:2611\u20138.","journal-title":"N Engl J Med"},{"key":"4754_CR43","first-page":"217","volume":"11","author":"C Windsor","year":"2016","unstructured":"Windsor C, Herrett E, Smeeth L, Quint JK. No association between exacerbation frequency and stroke in patients with COPD. Int J Chron Obstr Pulmon Dis. 2016;11:217\u201325.","journal-title":"Int J Chron Obstr Pulmon Dis"},{"key":"4754_CR44","doi-asserted-by":"publisher","first-page":"1851","DOI":"10.2147\/COPD.S311826","volume":"16","author":"J de Miguel-D\u00edez","year":"2021","unstructured":"de Miguel-D\u00edez J, L\u00f3pez-de-Andr\u00e9s A, Jim\u00e9nez-Garc\u00eda R, Hern\u00e1ndez-Barrera V, Jim\u00e9nez-Trujillo I, Ji Z, et al. Sex differences in the incidence and outcomes of COPD patients hospitalized with ischemic stroke in Spain: a population-based observational study. Int J Chron Obstr Pulmon Dis. 2021;16:1851\u201362.","journal-title":"Int J Chron Obstr Pulmon Dis"},{"key":"4754_CR45","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1186\/s12931-020-1312-7","volume":"21","author":"EL Axson","year":"2020","unstructured":"Axson EL, Ragutheeswaran K, Sundaram V, Bloom CI, Bottle A, Cowie MR, et al. Hospitalisation and mortality in patients with comorbid COPD and heart failure: a systematic review and meta- analysis. Respir Res. 2020;21:54.","journal-title":"Respir Res"},{"key":"4754_CR46","unstructured":"AstraZeneca. A study evaluating the efficacy of budesonide, glycopyrronium and formoterol fumarate metered dosed inhaler on cardiopulmonary outcomes in chronic obstructive pulmonary disease (THARROS). 2024. Available: https:\/\/clinicaltrials.gov\/study\/NCT06283966. Accessed 11 Feb 2025."},{"key":"4754_CR47","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1002\/pds.4212","volume":"26","author":"M Iwagami","year":"2017","unstructured":"Iwagami M, Tomlinson LA, Mansfield KE, McDonald HI, Smeeth L, Nitsch D. Prevalence, incidence, indication, and choice of antidepressants in patients with and without chronic kidney disease: a matched cohort study in UK Clinical Practice Research Datalink. Pharmacoepidemiol Drug Saf. 2017;26:792\u2013801.","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"4754_CR48","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0151357","volume":"11","author":"KJ Rothnie","year":"2016","unstructured":"Rothnie KJ, M\u00fcllerov\u00e1 H, Hurst JR, Smeeth L, Davis K, Thomas SL, et al. Validation of the recording of acute exacerbations of COPD in UK primary care electronic healthcare records. PLoS ONE. 2016;11:e0151357.","journal-title":"PLoS ONE"},{"key":"4754_CR49","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1003106","volume":"17","author":"R Mathur","year":"2020","unstructured":"Mathur R, Farmer RE, Eastwood SV, Chaturvedi N, Douglas I, Smeeth L. Ethnic disparities in initiation and intensification of diabetes treatment in adults with type 2 diabetes in the UK, 1990\u20132017: a cohort study. PLoS Med. 2020;17:e1003106.","journal-title":"PLoS Med"}],"container-title":["BMC Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12916-026-04754-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12916-026-04754-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12916-026-04754-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T11:03:33Z","timestamp":1775819013000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12916-026-04754-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,4]]},"references-count":49,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["4754"],"URL":"https:\/\/doi.org\/10.1186\/s12916-026-04754-7","relation":{},"ISSN":["1741-7015"],"issn-type":[{"value":"1741-7015","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,4]]},"assertion":[{"value":"3 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"CPRD has NHS Health Research Authority (HRA) Research Ethics Committee (REC) approval to allow the collection and release of anonymised primary care data for observational research (NHS HRA REC reference number: 05\/MRE04\/87). Each year CPRD obtains Sect.\u00a0251 regulatory support through the HRA Confidentiality Advisory Group(CAG), to enable patient identifiers, without accompanying clinical data, to flow from CPRD contributing GP practices in England to NHS Digital, for the purposes of data linkage (CAG reference number: 21\/CAG\/0008). The protocol for this research was approved by CPRD\u2019s Research Data Governance (RDG) Process (protocol number: 22_002514) and the approved protocol is available upon request. Linked pseudonymised data was provided for this study by CPRD. Data is linked by NHS Digital, the statutory trusted third party for linking data, using identifiable data held only by NHS Digital. Select general practices consent to this process at a practice level with individual patients having the right to opt-out. Further information on availing data is available in Additional file 1.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"No individual-level data is available within this publication; all data are summary statistics. In addition, CPRD policy dictates that no table cell may report fewer than five events to protect participants\u2019 identities.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Mixed competing interests: All authors have completed the ICMJE uniform disclosure form at http:\/\/www.icmje.org\/disclosure-of-interest\/and declare: AEI has received institutional grants from the British Heart Foundation (BHF). ELG has nothing to disclose. CK has nothing to disclose. UT is supported by research grants from the Medical Research Council, Royal Society and NIHR Imperial Biomedical Research Centre. UT is a freelance research editor at the British Medical Journal. HM is an employee of AstraZeneca and owns shares and stock options of AstraZeneca. JKQ has been supported by institutional research grants from the Medical Research Council, NIHR, Health Data Research, GSK, BI, AZ, Insmed, Sanofi and received personal fees for advisory board participation, consultancy or speaking fees from GlaxoSmithKline, Evidera, Chiesi, AstraZeneca. This research was supported by the NIHR Imperial Biomedical Research Centre (BRC).","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"221"}}