{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T23:22:57Z","timestamp":1790292177503,"version":"4.1.0"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T00:00:00Z","timestamp":1765584000000},"content-version":"vor","delay-in-days":468,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,9,1]],"date-time":"2024-09-01T00:00:00Z","timestamp":1725148800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013373","name":"National Institute for Health Research Oxford Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013373","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001320","name":"Wolfson Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001320","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013373","name":"National Institute for Health Research Oxford Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013373","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001320","name":"Wolfson Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001320","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction:<\/jats:title>\n                    <jats:p>Cerebral blood flow (CBF) declines with age and abnormalities in CBF are associated with age-related cerebrovascular disease and neurodegeneration. Women have higher CBF than men, although this sex-difference diminishes to some extent with age in healthy subjects. The physiological drivers of these age\/sex differences are uncertain, but might be secondary to age and sex-differences in haemoglobin (Hb) level. Hb levels are inversely correlated with CBF, are lower in women, and decline with age in men, but the interrelations between these factors have not been explored systematically either in healthy subjects or across the full age-range in patients with vascular risk factors. We aimed to determine the age-specific interrelations between sex, Hb, and CBF velocity in a large cohort of patients with cerebrovascular disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and methods:<\/jats:title>\n                    <jats:p>In patients with a recent transient ischaemic attack or minor stroke (Oxford Vascular Study) and no ipsilateral or contralateral stenosis of the carotid or intracranial arteries, we related peak-systolic velocity (PSV) and other parameters on transcranial Doppler ultrasound (TCD) of the middle cerebral artery to sex, age, Hb and vascular risk factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Of 958 eligible subjects (mean age\/SD\u2009=\u200968.04\/14.26, 53.2% male), younger women (age\u2009&amp;lt;\u200955\u2009years) had higher CBF velocities than men (mean sex difference in PSV at age\u2009&amp;lt;\u200955 years\u2009=\u200916.31\u2009cm\/s; p\u2009&amp;lt;\u20090.001), but this difference declined with age (interaction p\u2009&amp;lt;\u20090.001), such that it was no longer significant at age 75\u201384 (\u2206PSV\u2009=\u20093.26\u2009cm\/s; p\u2009=\u20090.12) and was reversed at age\u2009\u2a7e\u200985 (\u2206PSV\u2009=\u2009\u22127.42\u2009cm\/s; p\u2009=\u20090.05). These changes mirrored trends in levels of Hb, which were higher in men at age\u2009&amp;lt;\u200955 (\u2206Hb\u2009=\u20091.92\u2009g\/dL; p\u2009&amp;lt;\u20090.001), but steadily decreased with age in men but not in women (interaction p\u2009&amp;lt;\u20090.001), with no residual sex-difference at age\u2009\u2a7e\u200985 (\u2206Hb\u2009=\u20090.12\u2009g\/dL; p\u2009=\u20090.70). There was an inverse correlation between Hb and PSV in both women and men (both p\u2009\u2a7d\u20090.01), and the sex-difference in PSV at age\u2009&amp;lt;\u200955 was substantially diminished after adjustment for Hb (\u2206PSV\u2009=\u20096.92; p\u2009=\u20090.036; \u2206PSV\u2009=\u20095.92, p\u2009=\u20090.13 with further adjustment for end-tidal CO2). In contrast, the sex difference in PSV was unaffected by adjustment for systolic and diastolic blood pressure, heart rate, and vascular risk factors (history of hypertension, diabetes, hyperlipidaemia and smoking).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion:<\/jats:title>\n                    <jats:p>CBF velocity is strongly correlated with Hb level at all ages, and sex-differences in CBF velocity appear to be explained in major part by age-related sex-differences in Hb.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/23969873241245631","type":"journal-article","created":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T07:10:28Z","timestamp":1713424228000},"page":"772-780","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":28,"title":["Age-specific sex-differences in cerebral blood flow velocity in relation to haemoglobin levels"],"prefix":"10.1093","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1582-6724","authenticated-orcid":false,"given":"Sara","family":"Mazzucco","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3636-8355","authenticated-orcid":false,"given":"Linxin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Assuncao","family":"Tuna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9739-9211","authenticated-orcid":false,"given":"Peter M","family":"Rothwell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"On Behalf of the Oxford Vascular Study Phenotyped cohort","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,9,1]]},"reference":[{"key":"2026012113091814500_bibr1-23969873241245631","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.1152\/japplphysiol.00939.2020","article-title":"Regional and interindividual relationships between cerebral perfusion and oxygen metabolism","volume":"130","author":"Henriksen","year":"2021","journal-title":"J Appl Physiol"},{"key":"2026012113091814500_bibr2-23969873241245631","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1038\/jcbfm.1988.133","article-title":"Sex differences in regional cerebral blood flow","volume":"8","author":"Rodriguez","year":"1988","journal-title":"J Cereb Blood Flow Metab"},{"key":"2026012113091814500_bibr3-23969873241245631","doi-asserted-by":"crossref","first-page":"2433","DOI":"10.1177\/0271678X16668536","article-title":"Sex differences of human cortical blood flow and energy metabolism","volume":"37","author":"Aanerud","year":"2017","journal-title":"J Cereb Blood Flow Metab"},{"key":"2026012113091814500_bibr4-23969873241245631","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1177\/0271678X231153741","article-title":"Cerebral blood flow and cerebrovascular resistance across the adult lifespan: a multimodality approach","volume":"43","author":"Tomoto","year":"2023","journal-title":"J Cereb Blood Flow Metab"},{"key":"2026012113091814500_bibr5-23969873241245631","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1111\/j.1552-6569.2012.00711.x","article-title":"Transcranial Doppler velocities in a large, healthy population","volume":"23","author":"Tegeler","year":"2013","journal-title":"J Neuroimaging"},{"key":"2026012113091814500_bibr6-23969873241245631","doi-asserted-by":"crossref","first-page":"213","DOI":"10.2214\/ajr.172.1.9888770","article-title":"Transcranial color Doppler sonography of basal cerebral arteries in 182 healthy subjects: age and sex variability and normal reference values for blood flow parameters","volume":"172","author":"Krejza","year":"1999","journal-title":"Am J Roentgenol"},{"key":"2026012113091814500_bibr7-23969873241245631","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1159\/000078503","article-title":"Cerebral haemodynamics in the elderly: the Rotterdam study","volume":"23","author":"Bakker","year":"2004","journal-title":"Neuroepidemiology"},{"key":"2026012113091814500_bibr8-23969873241245631","doi-asserted-by":"crossref","first-page":"158","DOI":"10.7326\/0003-4819-107-2-158","article-title":"Disparate cardiovascular findings in men and women with essential hypertension","volume":"107","author":"Messerli","year":"1987","journal-title":"Ann Intern Med"},{"key":"2026012113091814500_bibr9-23969873241245631","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.7863\/ultra.15.10040","article-title":"Cerebral hemodynamics in the elderly: a transcranial Doppler study in the Einstein aging study cohort","volume":"35","author":"Yang","year":"2016","journal-title":"J Ultrasound Med"},{"key":"2026012113091814500_bibr10-23969873241245631","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1111\/bjh.16430","article-title":"Blood counts in adult and elderly individuals: defining the norms over eight decades of life","volume":"189","author":"Zierk","year":"2020","journal-title":"Br J Haematol"},{"key":"2026012113091814500_bibr11-23969873241245631","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1038\/jcbfm.2010.13","article-title":"Interindividual variations of cerebral blood flow, oxygen delivery, and metabolism in relation to hemoglobin concentration measured by positron emission tomography in humans","volume":"30","author":"Ibaraki","year":"2010","journal-title":"J Cereb Blood Flow Metab"},{"key":"2026012113091814500_bibr12-23969873241245631","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1161\/01.STR.19.5.594","article-title":"Autoregulatory capacity and the effect of isovolemic hemodilution on local cerebral blood flow","volume":"19","author":"von Kummer","year":"1988","journal-title":"Stroke"},{"key":"2026012113091814500_bibr13-23969873241245631","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1111\/bjh.14424","article-title":"The severity of anaemia depletes cerebrovascular dilatory reserve in children with sickle cell disease: a quantitative magnetic resonance imaging study","volume":"176","author":"Kosinski","year":"2017","journal-title":"Br J Haematol"},{"key":"2026012113091814500_bibr14-23969873241245631","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1038\/jcbfm.1992.105","article-title":"Increased cerebral blood flow in anemic patients on long-term hemodialytic treatment","volume":"12","author":"Vorstrup","year":"1992","journal-title":"J Cereb Blood Flow Metab"},{"key":"2026012113091814500_bibr15-23969873241245631","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1016\/S0140-6736(85)92145-2","article-title":"Regulation of cerebral blood flow in response to changes in blood viscosity","volume":"1","author":"Brown","year":"1985","journal-title":"Lancet"},{"key":"2026012113091814500_bibr16-23969873241245631","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1056\/NEJM199807023390102","article-title":"Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography","volume":"339","author":"Adams","year":"1998","journal-title":"New Engl J Med"},{"key":"2026012113091814500_bibr17-23969873241245631","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1161\/hc1002.105133","article-title":"Sex differences in hospital mortality after coronary artery bypass surgery evidence for a higher mortality in younger women","volume":"105","author":"Vaccarino","year":"2002","journal-title":"Circulation"},{"key":"2026012113091814500_bibr18-23969873241245631","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/S0140-6736(04)15785-1","article-title":"Endarterectomy for symptomatic carotid stenosis in relation to clinical subgroups and timing of surgery","volume":"363","author":"Rothwell","year":"2004","journal-title":"Lancet"},{"key":"2026012113091814500_bibr19-23969873241245631","doi-asserted-by":"crossref","first-page":"2482","DOI":"10.1016\/S0140-6736(17)30639-6","article-title":"Morphological suitability for endovascular repair, non-intervention rates, and operative mortality in women and men assessed for intact abdominal aortic aneurysm repair: systematic reviews with meta-analysis","volume":"389","author":"Ulug","year":"2017","journal-title":"Lancet"},{"key":"2026012113091814500_bibr20-23969873241245631","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1161\/01.STR.25.4.793","article-title":"Comparison of flow and velocity during dynamic autoregulation testing in humans","volume":"25","author":"Newell","year":"1994","journal-title":"Stroke"},{"key":"2026012113091814500_bibr21-23969873241245631","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1177\/23969873211039716","article-title":"Age-specific cerebral haemodynamic effects of early blood pressure lowering after transient ischaemic attack and non-disabling stroke","volume":"6","author":"Mazzucco","year":"2021","journal-title":"Eur Stroke J"},{"key":"2026012113091814500_bibr22-23969873241245631","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1016\/S0140-6736(05)67702-1","article-title":"Population-based study of event-rate, incidenc.e, case fatality, and mortality for all acute vascular events in all arterial territories (Oxford vascular study)","volume":"366","author":"Rothwell","year":"2005","journal-title":"Lancet"},{"key":"2026012113091814500_bibr23-23969873241245631","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1111\/j.1552-6569.2006.00083.x","article-title":"The Spencer\u2019s curve: clinical implications of a classic hemodynamic model","volume":"17","author":"Alexandrov","year":"2007","journal-title":"J Neuroimaging"},{"key":"2026012113091814500_bibr24-23969873241245631","doi-asserted-by":"crossref","first-page":"403","DOI":"10.7863\/jum.1990.9.7.403","article-title":"Side-to-side differences and day-to-day variations of transcranial Doppler parameters in normal subjects","volume":"9","author":"Sorteberg","year":"1990","journal-title":"J Ultrasound Med"},{"key":"2026012113091814500_bibr25-23969873241245631","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1161\/01.STR.32.1.30","article-title":"Effect of endogenous estrogen on blood flow through carotid arteries","volume":"32","author":"Krejza","year":"2001","journal-title":"Stroke"},{"key":"2026012113091814500_bibr26-23969873241245631","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1093\/brain\/awx161","article-title":"Cerebrovascular abnormalities in Alzheimer\u2019s dementia: a more tractable treatment target?","volume":"140","author":"Markus","year":"2017","journal-title":"Brain"},{"key":"2026012113091814500_bibr27-23969873241245631","doi-asserted-by":"crossref","first-page":"2133","DOI":"10.1161\/01.CIR.103.17.2133","article-title":"Sex differences in neurological outcomes and mortality after cardiac surgery. A society of thoracic surgery national database report","volume":"103","author":"Hogue","year":"2001","journal-title":"Circulation"},{"key":"2026012113091814500_bibr28-23969873241245631","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1111\/anae.13877","article-title":"Diagnostic criteria for pre-operative anaemia-time to end sex discrimination","volume":"72","author":"Butcher","year":"2017","journal-title":"Anaesthesia"},{"key":"2026012113091814500_bibr29-23969873241245631","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1016\/0002-8703(94)90679-3","article-title":"Hematocrit and the risk of cardiovascular disease\u2013the Framingham study: a 34-year follow-up","volume":"127","author":"Gagnon","year":"1994","journal-title":"Am Heart J"},{"key":"2026012113091814500_bibr30-23969873241245631","doi-asserted-by":"crossref","DOI":"10.1212\/WNL.0000000000008003","article-title":"Hemoglobin and anemia in relation to dementia risk and accompanying changes on brain MRI","volume":"93","author":"Wolters","year":"2019","journal-title":"Neurology"},{"key":"2026012113091814500_bibr31-23969873241245631","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1001\/archneurol.2010.367","article-title":"Smoking and risk of amyotrophic lateral sclerosis. A pooled analysis of 5 prospective cohorts","volume":"68","author":"Wang","year":"2011","journal-title":"Arch Neurol"},{"key":"2026012113091814500_bibr32-23969873241245631","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1017\/S0022172400043370","article-title":"Iron in human nutrition","volume":"36","author":"Widdowson","year":"1936","journal-title":"J Hyg"},{"key":"2026012113091814500_bibr33-23969873241245631","doi-asserted-by":"crossref","DOI":"10.1016\/S2352-3026(21)00351-3","article-title":"Sex specific definitions of anaemia contribute to health inequity and sociomedical injustice","volume":"9","author":"Weyand","year":"2022","journal-title":"Lancet Haematol"},{"key":"2026012113091814500_bibr34-23969873241245631","unstructured":"WHO. The urgent need to implement patient blood management: policy brief, https:\/\/www.who.int\/publications\/i\/item\/9789240035744 (2021, accessed\u20094\u2009January\u20092024)."}],"container-title":["European Stroke Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/23969873241245631","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/23969873241245631","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/esj\/article-pdf\/9\/3\/772\/64649040\/23969873241245631.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/esj\/article-pdf\/9\/3\/772\/64649040\/23969873241245631.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T18:10:01Z","timestamp":1769019001000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/esj\/article\/9\/3\/772\/8268973"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,1]]},"references-count":34,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,9,1]]}},"URL":"https:\/\/doi.org\/10.1177\/23969873241245631","relation":{},"ISSN":["2396-9873","2396-9881"],"issn-type":[{"value":"2396-9873","type":"print"},{"value":"2396-9881","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,9,1]]},"published":{"date-parts":[[2024,9,1]]}}}