{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T23:50:40Z","timestamp":1770681040254,"version":"3.49.0"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,11,7]],"date-time":"2017-11-07T00:00:00Z","timestamp":1510012800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007405","name":"Hjerteforeningen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007405","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Intern Med"],"published-print":{"date-parts":[[2018,3]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>Use of proton pump inhibitors (PPI<\/jats:styled-content>s) has been associated with cardiovascular disease amongst patients not on antiplatelet therapy. The associations of PPI<\/jats:styled-content> use, duration and dose, with risk of first\u2010time ischemic stroke and myocardial infarction (MI<\/jats:styled-content>) are poorly understood.<\/jats:p><\/jats:sec>Methods<\/jats:title>All Danish individuals with no prior history of MI<\/jats:styled-content> or stroke, who had an elective upper gastrointestinal endoscopy performed between 1997 and 2012, were identified from nationwide registries. We used multiple Poisson regression to test associations with current PPI<\/jats:styled-content> use and its dose and used multiple cause\u2010specific Cox regression and g\u2010formula methods to analyze long\u2010term use.<\/jats:p><\/jats:sec>Results<\/jats:title>Amongst 214\u00a0998 individuals, during a median follow\u2010up of 5.8\u00a0years, there were 7916 ischemic strokes and 5608 MI<\/jats:styled-content>s. Current PPI<\/jats:styled-content> exposure was associated with significantly higher rates of both ischemic stroke (Hazard ratio (HR<\/jats:styled-content>) 1.13; 95% confidence interval (CI<\/jats:styled-content>) 1.08\u20131.19) and MI<\/jats:styled-content> (HR<\/jats:styled-content> 1.31, CI<\/jats:styled-content> 1.23\u20131.39) after adjusting for age, sex, comorbidities and concomitant medication. High\u2010dose PPI<\/jats:styled-content> was associated with increased rates of ischemic stroke (HR<\/jats:styled-content> 1.31, CI<\/jats:styled-content> 1.21\u20131.42) and MI<\/jats:styled-content> (HR<\/jats:styled-content> 1.43, CI<\/jats:styled-content> 1.30\u20131.57). Histamine H2 receptor antagonists (H2RA<\/jats:styled-content>s) use was not significantly associated with ischemic stroke (HR<\/jats:styled-content> 1.02, CI<\/jats:styled-content> 0.84\u20131.24) or MI<\/jats:styled-content> (HR<\/jats:styled-content> 1.15, CI<\/jats:styled-content> 0.92\u20131.43). Long\u2010term users of PPI<\/jats:styled-content>s, compared with nonusers, had a 29% (CI<\/jats:styled-content> 5%\u201059%) greater absolute risk of ischemic stroke and a 36% (CI<\/jats:styled-content> 7%\u201073%) greater risk of MI<\/jats:styled-content> within a 6\u2010month period.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Use of PPI<\/jats:styled-content>s was associated with increased risks of first\u2010time ischemic stroke and MI<\/jats:styled-content>, particularly amongst long\u2010term users and at high doses.<\/jats:p><\/jats:sec>","DOI":"10.1111\/joim.12698","type":"journal-article","created":{"date-parts":[[2017,10,12]],"date-time":"2017-10-12T15:12:33Z","timestamp":1507821153000},"page":"268-281","source":"Crossref","is-referenced-by-count":76,"title":["Long\u2010term use of proton pump inhibitors, dose\u2013response relationship and associated risk of ischemic stroke and myocardial infarction"],"prefix":"10.1111","volume":"283","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0564-0237","authenticated-orcid":false,"given":"T. S. G.","family":"Sehested","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Epidemiology and Research The Danish Heart Foundation Copenhagen K Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T. A.","family":"Gerds","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Epidemiology and Research The Danish Heart Foundation Copenhagen K Denmark"},{"name":"Department of\u00a0Biostatistics Copenhagen University Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E. L.","family":"Fosb\u00f8l","sequence":"additional","affiliation":[{"name":"The Heart Centre Copenhagen University Hospital Rigshospitalet Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P. W.","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Epidemiology and Research The Danish Heart Foundation Copenhagen K Denmark"},{"name":"Department of Health Research and Policy Department of Medicine Stanford University School of Medicine Stanford CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. G.","family":"Charlot","sequence":"additional","affiliation":[{"name":"Department of Cardiology Copenhagen University Hospital Herlev and Gentofte Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Carlson","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Epidemiology and Research The Danish Heart Foundation Copenhagen K Denmark"},{"name":"Department of Internal Medicine Gastroenterology section Holbaek Hospital Holbaek Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. A.","family":"Hlatky","sequence":"additional","affiliation":[{"name":"Department of Health Research and Policy Department of Medicine Stanford University School of Medicine Stanford CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Torp\u2010Pedersen","sequence":"additional","affiliation":[{"name":"Department of Health, Science and Technology Department of Cardiology and Epidemiology\/Biostatistics Aalborg University Aalborg University Hospital Hellerup Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G. H.","family":"Gislason","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Epidemiology and Research The Danish Heart Foundation Copenhagen K Denmark"},{"name":"The Heart Centre Copenhagen University Hospital Rigshospitalet Denmark"},{"name":"The National Institute of Public Health University of Southern Denmark Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,11,7]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"1","article-title":"Rapidly increasing prescribing of proton pump inhibitors in primary care despite interventions: a nationwide observational study","volume":"4788","author":"Haastrup P","year":"2014","journal-title":"Eur J Gen Pract"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0056060"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.1969"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.4043"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgs.14528"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejim.2010.11.009"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2710.2000.00312.x"},{"key":"e_1_2_9_9_1","first-page":"e228","article-title":"Magnitude and economic effect of overuse of antisecretory therapy in the ambulatory care setting","volume":"16","author":"Heidelbaugh JJ","year":"2010","journal-title":"Am J Manag Care"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2017.101"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0124653"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2014.09.036"},{"key":"e_1_2_9_13_1","first-page":"1","article-title":"Proton pump inhibitor monotherapy and the risk of cardiovascular events in patients with gastro\u2010esophageal reflux disease: a meta\u2010analysis","volume":"29","author":"Sun S","year":"2016","journal-title":"Neurogastroenterol Motil"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.308807"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.2147\/CLEP.S91125"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.2147\/CLEP.S49354"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.d124"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurpub\/cki115"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2016-012832"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1159\/000102143"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v038.i05"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.2307\/2532098"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.EDE.0000081989.82616.7d"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0084890"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-014-1779-6"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCOUTCOMES.114.001177"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.115.002245"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-153-6-201009210-00005"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.032912"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.003602"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000126823.07732.D5"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1177\/1358863X14568444"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17040454"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2466"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2015.7193"},{"key":"e_1_2_9_36_1","first-page":"1","article-title":"Association of proton pump inhibitors with risk of dementia","volume":"73","author":"Gomm W","year":"2016","journal-title":"JAMA Neurol"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1007964"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11894-008-0098-4"},{"key":"e_1_2_9_39_1","unstructured":"Anon. 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