{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T20:41:15Z","timestamp":1740170475003,"version":"3.37.3"},"reference-count":28,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T00:00:00Z","timestamp":1707955200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>Proton-pump inhibitors (PPIs) are prescribed to treat gastric acid<jats:bold>-<\/jats:bold>related diseases, while they may also have potential risks to population health. Recent studies suggested that a potential mechanism explaining the association between PPIs and cardiovascular diseases (CVD) includes the inhibition of the nitrate<jats:bold>-<\/jats:bold>nitrite<jats:bold>-<\/jats:bold>nitric oxide (NO) pathway. However, previous observational studies showed controversial results of the association. In addition, the inhibition of the NO pathway due to PPIs use may lead to peripheral vascular diseases (PVD); however, none of the studies explore the PPI-PVD association. Therefore, this study aimed to evaluate the association of PPIs with circulatory diseases (CVD, ischemic strokes or IS, and PVD).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>We conducted a retrospective hospital<jats:bold>-<\/jats:bold>based cohort study from Oct 2010 to Sep 2017 in Songkhla province, Thailand. PPIs and histamine 2<jats:bold>-<\/jats:bold>receptor antagonists <jats:bold>(<\/jats:bold>H2RAs<jats:bold>)<\/jats:bold> prescriptions were collected from electronic pharmacy records, while diagnostic outcomes were retrieved from electronic medical records at Songklanagarind hospital. Patients were followed up with an on<jats:bold>-<\/jats:bold>treatment approach. Cox proportional hazard models were applied to measure the association comparing PPIs <jats:italic>vs<\/jats:italic> H2RAs after 1:1 propensity<jats:bold>-<\/jats:bold>score<jats:bold>-<\/jats:bold>matching. Sub<jats:bold>-<\/jats:bold>group analysis, multi<jats:bold>-<\/jats:bold>bias E<jats:bold>-<\/jats:bold>values, and array<jats:bold>-<\/jats:bold>based sensitivity analysis for some covariates were used to assess the robustness of associations.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>A total of 3,928 new PPIs and 3,928 H2RAs users were included in the 1:1 propensity score<jats:bold>-<\/jats:bold>matched cohort. As compared with H2RAs, the association of PPIs with CVD, IS, and PVD, the hazard ratios were 1.76 95% CI = [1.40\u20132.20] for CVD, 3.53 95% CI = [2.21\u20135.64] for ischemic strokes, and 17.07 95% CI = [13.82\u201376.25] for PVD. The association between PPIs and each outcome was significant with medication persistent ratio of over 50%. In addition, the association between PPIs and circulatory diseases was robust to unmeasured confounders (<jats:italic>i.e.<\/jats:italic>, smoking and alcohol).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>PPIs were associated with circulatory diseases, particularly ischemic strokes in this hospital-based cohort study, whereas, the strength of associations was robust to unmeasured confounders.<\/jats:p>\n<\/jats:sec>","DOI":"10.7717\/peerj.16892","type":"journal-article","created":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T09:36:15Z","timestamp":1707989775000},"page":"e16892","source":"Crossref","is-referenced-by-count":1,"title":["Risk of circulatory diseases associated with proton-pump inhibitors: a retrospective cohort study using electronic medical records in Thailand"],"prefix":"10.7717","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7316-0094","authenticated-orcid":true,"given":"Tanavij","family":"Pannoi","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Care, School of Pharmacy, Walailak University, Nakhornsrithammarat, Thailand"},{"name":"International Health Program, Institute of Public Health, National Yang Ming Chiao Tung University, Taipei, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chissanupong","family":"Promchai","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Songklanagarind Hospital, Prince of Songkhla University, Songkhla, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Penjamaporn","family":"Apiromruck","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Songklanagarind Hospital, Prince of Songkhla University, Songkhla, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suwikran","family":"Wongpraphairot","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Songklanagarind Hospital, Prince of Songkhla University, Songkhla, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaa-Hui","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, College of Pharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan"},{"name":"Institute of Public Health, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan"},{"name":"Institute of Hospital and Health Care Administration, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen-Chang","family":"Yang","sequence":"additional","affiliation":[{"name":"International Health Program, Institute of Public Health, National Yang Ming Chiao Tung University, Taipei, Taiwan"},{"name":"Institute of Environmental and Occupational Health Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan"},{"name":"Department of Occupational Medicine and Clinical Toxicology, Taipei Veterans General Hospital, Taipei, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Chi","family":"Pan","sequence":"additional","affiliation":[{"name":"International Health Program, Institute of Public Health, National Yang Ming Chiao Tung University, Taipei, Taiwan"},{"name":"Institute of Environmental and Occupational Health Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"4443","published-online":{"date-parts":[[2024,2,15]]},"reference":[{"issue":"2","key":"10.7717\/peerj.16892\/ref-1","doi-asserted-by":"publisher","first-page":"e12988","DOI":"10.1111\/nmo.12988","article-title":"Mechanisms contributing to increased cardiovascular 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