{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:07:43Z","timestamp":1791461263881,"version":"4.3.4"},"reference-count":36,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T00:00:00Z","timestamp":1653436800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["849200006"],"award-info":[{"award-number":["849200006"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["116030"],"award-info":[{"award-number":["116030"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010767","name":"Innovative Medicines Initiative 2 Joint Undertaking","doi-asserted-by":"publisher","award":["849200006"],"award-info":[{"award-number":["849200006"]}],"id":[{"id":"10.13039\/501100010767","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010767","name":"Innovative Medicines Initiative 2 Joint Undertaking","doi-asserted-by":"publisher","award":["116030"],"award-info":[{"award-number":["116030"]}],"id":[{"id":"10.13039\/501100010767","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Union\u2019s Horizon 2020 Research and Innovation Programme and EFPIA","award":["849200006"],"award-info":[{"award-number":["849200006"]}]},{"name":"European Union\u2019s Horizon 2020 Research and Innovation Programme and EFPIA","award":["116030"],"award-info":[{"award-number":["116030"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Background: Metoprolol, a beta-blocker, is used to reduce the heart rate. Although it has been demonstrated that the metoprolol plasma concentration is higher in women than in men, the same dose is recommended. In this study, we investigated whether the metoprolol concentration was associated with a stronger heart-rate reduction and bradycardia in women than in men. Methods: This study is part of the Rotterdam Study (RS), a population-based prospective cohort study. Blood samples from a random subset of 2000 participants were used to assess metoprolol plasma levels. An analysis of heart rate (beats per minute, bpm) and bradycardia (&lt;60 bpm) was performed in metoprolol users with an ECG at the day of blood collection to study sex-specific differences in heart rate and the risk of bradycardia. Results: In total, 40 women and 39 men were included. There was a statistically significant association between metoprolol concentration and heart rate in women (p-value: 0.014) but not in men (p-value: 0.639). Furthermore, women in the highest concentration group had a more than 15-times-higher risk of bradycardia than women in the lowest concentration group (OR = 15.6; 95% CI = 1.1, 217.3); however, this was not seen in men (OR = 1.3; 95% CI = 0.1, 12.4). After adjustment for age, BMI, time between blood sample and ECG, hypertension, myocardial infarction, heart failure, atrial fibrillation, digoxin use, and calcium channel blocker use, the association between concentration and bradycardia in women remained statistically significant. Conclusions: Women, but not men, had a statistically significantly lower heart rate at higher metoprolol plasma concentration and a statistically significantly increased risk of bradycardia.<\/jats:p>","DOI":"10.3390\/jpm12060870","type":"journal-article","created":{"date-parts":[[2022,5,27]],"date-time":"2022-05-27T07:05:07Z","timestamp":1653635107000},"page":"870","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Sex-Based Difference in the Effect of Metoprolol on Heart Rate and Bradycardia in a Population-Based Setting"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0534-4841","authenticated-orcid":false,"given":"Linda C.","family":"Hendriksen","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"},{"name":"Department of Clinical Pharmacy, Tergooi MC, 1213 XZ Hilversum, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5531-2621","authenticated-orcid":false,"given":"Grace","family":"Omes-Smit","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit C. P.","family":"Koch","sequence":"additional","affiliation":[{"name":"Department of Hospital Pharmacy, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Arfan","family":"Ikram","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno H.","family":"Stricker","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1421-6246","authenticated-orcid":false,"given":"Loes E.","family":"Visser","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"},{"name":"Department of Hospital Pharmacy, Erasmus MC, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands"},{"name":"Department of Clinical Pharmacy, Haga Teaching Hospital, 2545 AA The Hague, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1093\/ehjcvp\/pvw042","article-title":"Gender differences in the effects of cardiovascular drugs","volume":"3","author":"Tamargo","year":"2017","journal-title":"Eur. 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Womens Health"}],"container-title":["Journal of Personalized Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4426\/12\/6\/870\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:18:47Z","timestamp":1760138327000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4426\/12\/6\/870"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,25]]},"references-count":36,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["jpm12060870"],"URL":"https:\/\/doi.org\/10.3390\/jpm12060870","relation":{},"ISSN":["2075-4426"],"issn-type":[{"value":"2075-4426","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,25]]}}}