{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:10:18Z","timestamp":1792098618411,"version":"4.4.0"},"reference-count":33,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T00:00:00Z","timestamp":1647475200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001828","name":"Erasmus Universiteit Rotterdam","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001828","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003061","name":"Erasmus Medisch Centrum","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003061","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"name":"The Research Institute for Diseases in the Elderly"},{"name":"The Netherlands Genomics Initiative"},{"DOI":"10.13039\/501100002999","name":"Ministerie van Volksgezondheid, Welzijn en Sport","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002999","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003245","name":"Ministerie van Onderwijs, Cultuur en Wetenschap","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003245","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012517","name":"Directorate-General XII, Science, Research, and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012517","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Municipality of Rotterdam"}],"content-domain":{"domain":["www.plosmedicine.org"],"crossmark-restriction":false},"short-container-title":["PLoS Med"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Apart from blood pressure level itself, variation in blood pressure has been implicated in the development of stroke in subgroups at high cardiovascular risk. We determined the association between visit-to-visit blood pressure variability and stroke risk in the general population, taking into account the size and direction of variation and several time intervals prior to stroke diagnosis.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods and findings<\/jats:title>\n<jats:p>From 1990 to 2016, we included 9,958 stroke-free participants of the population-based Rotterdam Study in the Netherlands. This is a prospective cohort study including participants aged 45 years and older. Systolic blood pressure (SBP) variability was calculated as absolute SBP difference divided by mean SBP over 2 sequential visits (median 4.6 years apart). Directional SBP variability was defined as SBP difference over 2 visits divided by mean SBP. Using time-varying Cox proportional hazards models adjusted for age, sex, mean SBP, and cardiovascular risk factors, hazard ratios (HRs) for stroke up to January 2016 were estimated per SD increase and in tertiles of variability. We also conducted analyses with 3-, 6-, and 9-year intervals between variability measurement and stroke assessment. These analyses were repeated for diastolic blood pressure (DBP). The mean age of the study population was 67.4 \u00b1 8.2 years and 5,776 (58.0%) were women. During a median follow-up of 10.1 years, 971 (9.8%) participants had a stroke, including 641 ischemic, 89 hemorrhagic, and 241 unspecified strokes. SBP variability was associated with an increased risk of hemorrhagic stroke (HR per SD 1.27, 95% CI 1.05\u20131.54, <jats:italic>p<\/jats:italic> = 0.02) and unspecified stroke (HR per SD 1.21, 95% CI 1.09\u20131.34, <jats:italic>p &lt;<\/jats:italic> 0.001). The associations were stronger for all stroke subtypes with longer time intervals; the HR for any stroke was 1.29 (95% CI 1.21\u20131.36, <jats:italic>p &lt;<\/jats:italic> 0.001) at 3 years, 1.47 (95% CI 1.35\u20131.59, <jats:italic>p &lt;<\/jats:italic> 0.001) at 6 years, and 1.38 (95%CI 1.24\u20131.51, <jats:italic>p &lt;<\/jats:italic> 0.001) at 9 years. For DBP variability, we found an association with unspecified stroke risk. Both the rise and fall of SBP and the fall of DBP were associated with an increased risk for unspecified stroke. Limitations of the study include that, due to an average interval of 4 years between visits, our findings may not be generalizable to blood pressure variability over shorter periods.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>In this population-based study, we found that visit-to-visit blood pressure variation was associated with an increased risk of unspecified and hemorrhagic stroke, independent of direction of variation or mean blood pressure.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pmed.1003942","type":"journal-article","created":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T17:31:50Z","timestamp":1647538310000},"page":"e1003942","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":44,"title":["Visit-to-visit blood pressure variability and the risk of stroke in the Netherlands: A population-based cohort study"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5091-0534","authenticated-orcid":true,"given":"Alis","family":"Heshmatollah","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0207-3620","authenticated-orcid":true,"given":"Yuan","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4961-5631","authenticated-orcid":true,"given":"Lana","family":"Fani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4998-9609","authenticated-orcid":true,"given":"Peter J.","family":"Koudstaal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0372-8585","authenticated-orcid":true,"given":"M. Arfan","family":"Ikram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0173-9571","authenticated-orcid":true,"given":"M. Kamran","family":"Ikram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,3,17]]},"reference":[{"issue":"9623","key":"pmed.1003942.ref001","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1016\/S0140-6736(08)60655-8","article-title":"International Society of Hypertension. Global burden of blood-pressure-related disease, 2001","volume":"371","author":"CM Lawes","year":"2008","journal-title":"Lancet"},{"issue":"9718","key":"pmed.1003942.ref002","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1016\/S0140-6736(10)60309-1","article-title":"Limitations of the usual blood-pressure hypothesis and importance of variability, instability, and episodic hypertension","volume":"375","author":"PM Rothwell","year":"2010","journal-title":"Lancet"},{"issue":"12","key":"pmed.1003942.ref003","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1093\/ajh\/hpt167","article-title":"Visit-to-visit blood pressure variability, silent cerebral injury, and risk of stroke","volume":"26","author":"M Nagai","year":"2013","journal-title":"Am J Hypertens"},{"issue":"5","key":"pmed.1003942.ref004","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1161\/HYPERTENSIONAHA.114.03903","article-title":"Visit-to-visit variability of blood pressure and cardiovascular 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Kronish","year":"2016","journal-title":"Hypertension"},{"issue":"24","key":"pmed.1003942.ref007","doi-asserted-by":"crossref","first-page":"2243","DOI":"10.1093\/eurheartj\/ehx760","article-title":"Blood pressure variability and risk of cardiovascular events and death in patients with hypertension and different baseline risks","volume":"39","author":"MH Mehlum","year":"2018","journal-title":"Eur Heart J"},{"issue":"5","key":"pmed.1003942.ref008","doi-asserted-by":"crossref","first-page":"329","DOI":"10.7326\/M14-2803","article-title":"Visit-to-visit variability of blood pressure and coronary heart disease, stroke, heart failure, and mortality: a cohort study","volume":"163","author":"P Muntner","year":"2015","journal-title":"Ann Intern Med"},{"issue":"9718","key":"pmed.1003942.ref009","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/S0140-6736(10)60308-X","article-title":"Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic 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patients with cerebral infarction","volume":"7","author":"T Robinson","year":"1997","journal-title":"Cerebrovasc Dis"},{"key":"pmed.1003942.ref033","doi-asserted-by":"crossref","first-page":"b2393","DOI":"10.1136\/bmj.b2393","article-title":"Multiple imputation for missing data in epidemiological and clinical research: potential and pitfalls","volume":"338","author":"JA Sterne","year":"2009","journal-title":"BMJ"}],"container-title":["PLOS Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pmed.1003942","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,17]],"date-time":"2022-03-17T17:32:31Z","timestamp":1647538351000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pmed.1003942"}},"subtitle":[],"editor":[{"given":"Joshua 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