{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T22:01:12Z","timestamp":1792101672361,"version":"4.4.0"},"reference-count":42,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T00:00:00Z","timestamp":1661731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["PG\/16\/38\/32080"],"award-info":[{"award-number":["PG\/16\/38\/32080"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["206589\/Z\/17\/Z"],"award-info":[{"award-number":["206589\/Z\/17\/Z"]}],"id":[{"id":"10.13039\/100010269","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":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Beta\u2010blockers are beneficial in coronary artery disease but less so in stroke prevention and dementia, potentially due to reduced heart rate (HR). Cerebral pulsatility is strongly associated with cerebral small vessel disease (SVD) and may be increased by lower diastolic pressures resulting from longer cardiac cycles.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients 4\u20136\u2009weeks after TIA or non\u2010disabling stroke (Oxford Vascular Study) underwent 5\u2009minutes continuous monitoring of blood pressure (BP), electrocardiogram (ECG), and middle cerebral artery flow velocity (transcranial ultrasound). Beat\u2010to\u2010beat relationships between HR, blood pressure and Gosling's pulsatility index (MCA\u2010PI) are reported as beta\u2010coefficients from general linear models for each individual.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Across 759 patients, average MCA\u2010PI during monitoring was associated with lower HR and diastolic BP (DBP) and greater systolic BP (SBP) (\u2206MCA\u2010PI per 10\u2009bpm\/mmHg: \u22120.02, \u22120.04, 0.03, all <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), with HR particularly associated with low end\u2010diastolic cerebral velocity (0.86, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.014). Beat\u2010to\u2010beat HR was strongly associated with concurrent low DBP and high SBP, potentially mediating the association with greater beat\u2010to\u2010beat cerebral pulsatility (average \u2206MCA\u2010PI vs HR\/DBP\/SBP unadjusted: \u22120.062, \u22120.052, 0.0092; adjusted for concurrent BP: \u22120.039, \u22120.11, 0.041). The beat\u2010to\u2010beat association between HR and MCA\u2010PI increased with age, beta\u2010blockers, arterial stiffness, low HR (age\u2009&gt;\u200970\u2009+\u2009HR\u2009&lt;\u200965 vs age\u2009&lt;\u200970\u2009+\u2009HR\u2009&gt;\u200965: \u22120.081 vs \u22120.024, interaction <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), and severe SVD on MRI (age\u2009&gt;\u200970\u2009+\u2009severe vs age\u2009&lt;\u200970\u2009+\u2009none: \u22120.087 vs \u22120.047, interaction <jats:italic>p<\/jats:italic>\u00a0=\u00a00.03), with interactions between age, severe SVD, and low HR synergistically increasing MCA\u2010PI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Low HR is associated with greater cerebral pulsatility in patients with SVD, potentially mediated by lower diastolic blood flow and representing a novel potential treatment target. 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