<?xml version="1.0" encoding="utf-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD Journal Publishing DTD v2.3 20070202//EN" "journalpublishing.dtd">
<?covid-19-tdm?>
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" article-type="research-article" dtd-version="2.3" xml:lang="EN">
<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Neurol.</journal-id>
<journal-title>Frontiers in Neurology</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Neurol.</abbrev-journal-title>
<issn pub-type="epub">1664-2295</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fneur.2024.1501316</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Neurology</subject>
<subj-group>
<subject>Original Research</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Evaluation of circadian rhythm and prognostic variability pre-and post-CEA or CAS treatment in patients with carotid artery stenosis</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes">
<name><surname>Quan</surname> <given-names>Yi</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="corresp" rid="c001"><sup>&#x002A;</sup></xref>
<uri xlink:href="https://loop.frontiersin.org/people/901032/overview"/>
<role content-type="https://credit.niso.org/contributor-roles/conceptualization/"/>
<role content-type="https://credit.niso.org/contributor-roles/data-curation/"/>
<role content-type="https://credit.niso.org/contributor-roles/formal-analysis/"/>
<role content-type="https://credit.niso.org/contributor-roles/investigation/"/>
<role content-type="https://credit.niso.org/contributor-roles/methodology/"/>
<role content-type="https://credit.niso.org/contributor-roles/project-administration/"/>
<role content-type="https://credit.niso.org/contributor-roles/resources/"/>
<role content-type="https://credit.niso.org/contributor-roles/software/"/>
<role content-type="https://credit.niso.org/contributor-roles/supervision/"/>
<role content-type="https://credit.niso.org/contributor-roles/validation/"/>
<role content-type="https://credit.niso.org/contributor-roles/visualization/"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
</contrib>
<contrib contrib-type="author">
<name><surname>Wang</surname> <given-names>Zhongzhu</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<role content-type="https://credit.niso.org/contributor-roles/conceptualization/"/>
<role content-type="https://credit.niso.org/contributor-roles/data-curation/"/>
<role content-type="https://credit.niso.org/contributor-roles/formal-analysis/"/>
<role content-type="https://credit.niso.org/contributor-roles/methodology/"/>
<role content-type="https://credit.niso.org/contributor-roles/project-administration/"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
</contrib>
<contrib contrib-type="author">
<name><surname>Zhang</surname> <given-names>Tao</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<role content-type="https://credit.niso.org/contributor-roles/investigation/"/>
<role content-type="https://credit.niso.org/contributor-roles/software/"/>
<role content-type="https://credit.niso.org/contributor-roles/supervision/"/>
<role content-type="https://credit.niso.org/contributor-roles/validation/"/>
<role content-type="https://credit.niso.org/contributor-roles/visualization/"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
</contrib>
<contrib contrib-type="author">
<name><surname>Sui</surname> <given-names>Yanyong</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<role content-type="https://credit.niso.org/contributor-roles/conceptualization/"/>
<role content-type="https://credit.niso.org/contributor-roles/data-curation/"/>
<role content-type="https://credit.niso.org/contributor-roles/investigation/"/>
<role content-type="https://credit.niso.org/contributor-roles/project-administration/"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
</contrib>
<contrib contrib-type="author">
<name><surname>Zhang</surname> <given-names>Xin</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<role content-type="https://credit.niso.org/contributor-roles/project-administration/"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
</contrib>
<contrib contrib-type="author">
<name><surname>Ji</surname> <given-names>Xueliang</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<role content-type="https://credit.niso.org/contributor-roles/investigation/"/>
<role content-type="https://credit.niso.org/contributor-roles/project-administration/"/>
<role content-type="https://credit.niso.org/contributor-roles/resources/"/>
<role content-type="https://credit.niso.org/contributor-roles/visualization/"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
</contrib>
<contrib contrib-type="author">
<name><surname>Liu</surname> <given-names>Ao-fei</given-names></name>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
<uri xlink:href="https://loop.frontiersin.org/people/1962906/overview"/>
<role content-type="https://credit.niso.org/contributor-roles/data-curation/"/>
<role content-type="https://credit.niso.org/contributor-roles/formal-analysis/"/>
<role content-type="https://credit.niso.org/contributor-roles/resources/"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name><surname>Jiang</surname> <given-names>Weijian</given-names></name>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
<xref ref-type="corresp" rid="c001"><sup>&#x002A;</sup></xref>
<uri xlink:href="https://loop.frontiersin.org/people/1595887/overview"/>
<role content-type="https://credit.niso.org/contributor-roles/funding-acquisition/"/>
<role content-type="https://credit.niso.org/contributor-roles/investigation/"/>
<role content-type="https://credit.niso.org/contributor-roles/methodology/"/>
<role content-type="https://credit.niso.org/contributor-roles/project-administration/"/>
<role content-type="https://credit.niso.org/contributor-roles/resources/"/>
<role content-type="https://credit.niso.org/contributor-roles/supervision/"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
</contrib>
</contrib-group>
<aff id="aff1"><sup>1</sup><institution>Department of Neurosurgery, Peking University People&#x2019;s Hospital</institution>, <addr-line>Beijing</addr-line>, <country>China</country></aff>
<aff id="aff2"><sup>2</sup><institution>Qingdao Women and Children&#x2019;s Hospital</institution>, <addr-line>Qingdao, Shandong</addr-line>, <country>China</country></aff>
<aff id="aff3"><sup>3</sup><institution>Department of Vascular Neurosurgery, New Era Stroke Care and Research Institute, The PLA Rocket Force Characteristic Medical Center</institution>, <addr-line>Beijing</addr-line>, <country>China</country></aff>
<author-notes>
<fn fn-type="edited-by" id="fn0001"><p>Edited by: Hrvoje Budincevic, University Hospital Sveti Duh, Croatia</p></fn>
<fn fn-type="edited-by" id="fn0002"><p>Reviewed by: Marijana Lisak, Sisters of Charity Hospital, Croatia</p><p>Nange Jin, University of Houston, United States</p></fn>
<corresp id="c001">&#x002A;Correspondence: Yi Quan, <email>ilovejuncn@outlook.com</email>; Weijian Jiang, <email>jiangweijian2018@163.com</email></corresp>
</author-notes>
<pub-date pub-type="epub">
<day>06</day>
<month>01</month>
<year>2025</year>
</pub-date>
<pub-date pub-type="collection">
<year>2024</year>
</pub-date>
<volume>15</volume>
<elocation-id>1501316</elocation-id>
<history>
<date date-type="received">
<day>24</day>
<month>09</month>
<year>2024</year>
</date>
<date date-type="accepted">
<day>02</day>
<month>12</month>
<year>2024</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#x00A9; 2025 Quan, Wang, Zhang, Sui, Zhang, Ji, Liu and Jiang.</copyright-statement>
<copyright-year>2025</copyright-year>
<copyright-holder>Quan, Wang, Zhang, Sui, Zhang, Ji, Liu and Jiang</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p>
</license>
</permissions>
<abstract>
<sec id="sec1">
<title>Objective</title>
<p>Carotid artery stenosis, primarily caused by atherosclerosis, is a major risk factor for ischemic stroke. Carotid endarterectomy (CEA) and carotid artery stenting (CAS) are established interventions to reduce stroke risk and restore cerebral blood flow. However, the effect of these treatments on circadian rhythms, and their influence on stroke recovery, remains underexplored. This study aims to assess how disruptions in circadian rhythms&#x2014;specifically sleep quality and blood pressure variability&#x2014;impact recovery in patients undergoing CEA or CAS.</p>
</sec>
<sec id="sec2">
<title>Methods</title>
<p>We conducted a prospective study involving 177 patients with carotid artery stenosis, all treated with either CEA or CAS. Patients were followed for 90&#x202F;days post-treatment, with neurological outcomes evaluated using the NIHSS Stroke Scale (NIHSS). Circadian rhythm-related factors, including sleep quality (Pittsburgh Sleep Quality Index [PSQI]) and blood pressure variability (daytime systolic and nighttime diastolic BP), were assessed pre-and post-treatment. Stepwise regression was used to identify predictors of stroke recovery.</p>
</sec>
<sec id="sec3">
<title>Results</title>
<p>In a cohort of 177 patients with symptomatic carotid atherosclerotic stenosis, stepwise regression identified post-treatment changes in PSQI, nighttime diastolic blood pressure, and the presence of coronary heart disease as significant independent predictors of poor neurological outcomes (<italic>p</italic>&#x202F;&#x003C;&#x202F;0.001). Both CEA and CAS significantly improved daytime systolic (<italic>p</italic>&#x202F;&#x003C;&#x202F;0.01) and nighttime diastolic blood pressure (<italic>p</italic>&#x202F;&#x003C;&#x202F;0.01). Patients with poorer prognosis had higher post-treatment PSQI scores (<italic>p</italic>&#x202F;&#x003C;&#x202F;0.001). Additionally, increased physical activity after treatment was linked to improved neurological recovery.</p>
</sec>
<sec id="sec4">
<title>Conclusion</title>
<p>This study highlights the critical role of circadian rhythm regulation and cardiovascular health in stroke recovery following CEA or CAS. Stepwise regression analysis revealed that sleep quality, blood pressure stability, and coronary heart disease were key predictors of neurological outcomes, underscoring the importance of integrating circadian rhythm management into rehabilitation strategies. These results provide a robust scientific foundation for further investigation into the role of circadian rhythms in clinical practice.</p>
</sec>
</abstract>
<kwd-group>
<kwd>carotid artery stenosis</kwd>
<kwd>circadian rhythms</kwd>
<kwd>carotid endarterectomy</kwd>
<kwd>carotid artery stenting</kwd>
<kwd>Pittsburgh Sleep Quality Index</kwd>
<kwd>National Institutes of Health Stroke Scale</kwd>
<kwd>International Physical Activity Questionnaire</kwd>
</kwd-group>
<counts>
<fig-count count="0"/>
<table-count count="4"/>
<equation-count count="0"/>
<ref-count count="33"/>
<page-count count="8"/>
<word-count count="5392"/>
</counts>
<custom-meta-wrap>
<custom-meta>
<meta-name>section-at-acceptance</meta-name>
<meta-value>Stroke</meta-value>
</custom-meta>
</custom-meta-wrap>
</article-meta>
</front>
<body>
<sec sec-type="intro" id="sec5">
<label>1</label>
<title>Introduction</title>
<p>Carotid artery stenosis, primarily caused by atherosclerosis, contributes to 15&#x2013;20% of ischemic strokes, which are a major cause of morbidity and mortality worldwide (<xref ref-type="bibr" rid="ref1">1</xref>, <xref ref-type="bibr" rid="ref2">2</xref>). Carotid endarterectomy (CEA) and carotid artery stenting (CAS) effectively restore cerebral blood flow and reduce stroke risk in carotid artery stenosis patients (<xref ref-type="bibr" rid="ref2">2</xref>). Although these procedures are well-established for stroke prevention, their effects on circadian rhythms and patient prognosis remain insufficiently explored.</p>
<p>Circadian rhythms regulate essential physiological processes, including sleep&#x2013;wake cycles, metabolism, and cardiovascular function, playing a crucial role in stroke risk and recovery (<xref ref-type="bibr" rid="ref3">3</xref>, <xref ref-type="bibr" rid="ref4">4</xref>). Disruptions in circadian rhythms, particularly in blood pressure variability and sleep&#x2013;wake cycles, have been shown to be closely linked to cardiovascular and neurovascular diseases. Circadian rhythms refer to the periodic changes in physiological and psychological processes within a 24-h cycle, which are regulated by an endogenous biological clock (<xref ref-type="bibr" rid="ref5">5</xref>). Under normal conditions, blood pressure decreases at night and rises significantly in the morning, a phenomenon known as the &#x201C;morning surge.&#x201D; However, when circadian rhythms are disrupted&#x2014;due to factors such as sleep disorders, night shifts, or other lifestyle elements&#x2014;this may lead to abnormalities in blood pressure regulation, thus increasing the risk of cardiovascular diseases (<xref ref-type="bibr" rid="ref6">6</xref>).</p>
<p>These disruptions may increase stroke risk and impair recovery (<xref ref-type="bibr" rid="ref7">7</xref>, <xref ref-type="bibr" rid="ref8">8</xref>). Poor sleep quality and abnormal blood pressure patterns elevate stroke risk, whereas circadian rhythm stabilization may improve recovery outcomes (<xref ref-type="bibr" rid="ref9">9</xref>). Nevertheless, the specific effects of CEA and CAS on circadian rhythms remain poorly understood, requiring further investigation (<xref ref-type="bibr" rid="ref10">10</xref>). Previous studies have shown that circadian rhythms significantly impact recovery outcomes in stroke patients, with disruptions leading to increased variability in patient prognosis (<xref ref-type="bibr" rid="ref11">11</xref>, <xref ref-type="bibr" rid="ref12">12</xref>). However, the specific effects of circadian rhythm stabilization post-CEA or CAS on prognostic variability have not been systematically evaluated (<xref ref-type="bibr" rid="ref13">13</xref>, <xref ref-type="bibr" rid="ref14">14</xref>).</p>
<p>This study systematically evaluates the effects of CEA and CAS on circadian rhythms and clinical outcomes in patients with carotid artery stenosis. By analyzing changes in sleep quality, blood pressure variability, and recovery markers, this study aims to provide insights for developing personalized rehabilitation strategies to improve patient prognosis. Understanding the role of circadian rhythms in carotid artery stenosis can help create tailored treatment plans, ultimately improving clinical outcomes and quality of life for stroke survivors. This research addresses a crucial gap by investigating the impact of circadian rhythm stabilization on long-term recovery and its association with prognostic variability.</p>
</sec>
<sec sec-type="materials|methods" id="sec6">
<label>2</label>
<title>Method and materials</title>
<p>We conducted a prospective data collection and retrospective analysis of patients diagnosed with carotid artery stenosis who underwent carotid endarterectomy (CEA) or carotid artery stenting (CAS) at the New Era Stroke Care and Research Institute and approved by the Ethics Committee of the PLA Rocket Force Characteristic Medical Center from November 2011 to October 2023 as study subjects. Inclusion criteria were: (1) adults aged 18&#x2013;88&#x202F;years; (2) patient clinically diagnosed with symptomatic carotid artery stenosis; (3) patients or their legal representatives provided informed consent and agreed to participate in the study and follow-up; and (4) clinically stable patients suitable for surgery and follow-up. Exclusion criteria included: (1) patients with non-atherosclerotic stenosis, including moyamoya disease, arterial dissection, arteritis, etc.; (2) patients with severe heart disease, renal or liver insufficiency; (3) patients with other vascular diseases requiring concurrent vascular surgery; (4) patients with severe cognitive impairment, recent stroke, drug dependence, or poor compliance; and (5) patients with missing follow-up data or other conditions deemed unsuitable for the study by the researchers. Baseline information and medical history were collected upon patient admission, and follow-up data were obtained through telephone interviews or outpatient visits. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), daily blood pressure measurements were recorded, and physical activity levels were assessed using the International Physical Activity Questionnaire (IPAQ). Neurological recovery was assessed using the 90-day NIHSS score.</p>
<p>Descriptive statistics were used to summarize baseline characteristics and assessment indices. Paired t-tests or Mann&#x2013;Whitney U tests were applied to compare pre-and post-treatment differences. Univariate and multivariate analyses were performed to identify significant factors related to circadian rhythms and prognosis. Stepwise regression, based on the Akaike Information Criterion (AIC) (<xref ref-type="bibr" rid="ref15">15</xref>), was used to further examine potential influencing factors, with variables entered or removed according to their contribution to model fit. The formation steps of the stepwise regression model are detailed in the <xref ref-type="supplementary-material" rid="SM1">Supplementary Table</xref>. Potential confounders, such as age, gender, and comorbidities, were adjusted for in the regression models. Missing data were handled using multiple imputation, and outliers were addressed using robust statistical methods. Multiple comparisons were adjusted using the Bonferroni correction to control for false discovery rates. All statistical analyses were conducted using R version 4.0.3.</p>
<p>The primary outcome was the 90-day NIHSS score, dichotomized into two categories: 0&#x202F;=&#x202F;Good prognosis (NIHSS &#x2264;2) and 1&#x202F;=&#x202F;Poor prognosis (NIHSS &#x003E;2) (<xref ref-type="bibr" rid="ref16">16</xref>). Secondary outcomes included improvements in quality of life and changes in physical activity levels before and after treatment. Quality of life was assessed using the validated SF-36 questionnaire, while the IPAQ measured physical activity levels. Several key variables were included in the stepwise regression analysis to assess their impact on NIHSS outcomes. To capture circadian rhythm changes during neurological recovery, the primary independent variables were defined as follows: &#x0394;PSQI Change (Post-treatment PSQI Total - Pre-treatment PSQI Total), representing sleep quality change post-treatment, &#x0394;High-Intensity Activity Duration Change and Activity Frequency Change also representing physical activity change. Blood pressure assessment focused on daytime systolic blood pressure (SBP) and nighttime diastolic blood pressure (DBP). Daytime SBP was selected due to its relevance to cardiovascular load and vascular reactivity during active periods, while nighttime DBP was chosen as a marker of circadian rhythm regulation and vascular resistance during rest. These parameters were used to evaluate the effects of carotid interventions on circadian-related hemodynamic variability, which is crucial for stroke recovery (<xref ref-type="bibr" rid="ref17">17</xref>). Similarly, to monitor the continuous changes in these indicators, we calculated the following: &#x0394;Daytime Avg Systolic BP Change (Post-treatment Daytime Avg Systolic BP - Pre-treatment Daytime Avg Systolic BP), which reflects the change in daytime average systolic blood pressure; and &#x0394;Nighttime Avg Diastolic BP Change (Post-treatment Nighttime Avg Diastolic BP - Pre-treatment Nighttime Avg Diastolic BP), which reflects the change in nighttime average diastolic blood pressure.</p>
</sec>
<sec sec-type="results" id="sec7">
<label>3</label>
<title>Results</title>
<sec id="sec8">
<label>3.1</label>
<title>Patient characteristics and baseline descriptive statistics</title>
<p>We initially collected a total of 228 patients who met the inclusion criteria for the study. After applying the exclusion criteria, 177 patients diagnosed with atherosclerotic carotid artery stenosis were enrolled in the study. Of these, 85.31% were male and 14.69% were female, with a mean age of 65.48&#x202F;&#x00B1;&#x202F;9.55&#x202F;years. There were no statistically significant differences in the distribution of gender and age between the good prognosis group and the poor prognosis group.</p>
<p>In terms of medical history, 74.58% of patients had hypertension, 41.81% had diabetes, and 76.84% had hyperlipidemia. Coronary heart disease was present in 24.29% of the cohort, with no significant differences between the two prognosis groups. Additionally, 40.11% of patients were smokers, with a higher but non-significant smoking rate observed in the poor prognosis group (45.46%, <italic>p</italic>&#x202F;=&#x202F;0.149). Alcohol consumption was reported by 32.77% of patients, with no significant differences between the prognosis groups.</p>
<p>There were no significant differences in prognosis outcomes between the two treatment modalities (<italic>p</italic>&#x202F;=&#x202F;0.805), indicating that the choice of intervention did not significantly impact patient recovery. Pre-existing comorbidities, such as hypertension, diabetes, and hyperlipidemia, were considered during patient evaluation, but they did not show significant influence on the outcomes between the CEA and CAS groups (<xref ref-type="table" rid="tab1">Table 1</xref>).</p>
<table-wrap position="float" id="tab1">
<label>Table 1</label>
<caption>
<p>Baseline characteristics of patients with carotid artery stenosis stratified by NIHSS outcome (Good vs. Poor).</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top" rowspan="2">Factors</th>
<th align="center" valign="top" rowspan="2">Total (<italic>n</italic>&#x202F;=&#x202F;177)</th>
<th align="center" valign="top" colspan="2">NIHSS outcome (0&#x202F;=&#x202F;Good, 1&#x202F;=&#x202F;Poor)</th>
<th align="center" valign="top" rowspan="2">Z, &#x03C7;<sup>2</sup></th>
<th align="center" valign="top" rowspan="2"><italic>p</italic>-value</th>
</tr>
<tr>
<th align="center" valign="top">0 (<italic>n</italic>&#x202F;=&#x202F;89)</th>
<th align="center" valign="top">1 (<italic>n</italic>&#x202F;=&#x202F;88)</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="middle">Gender, <italic>n</italic> (%)</td>
<td/>
<td/>
<td/>
<td align="center" valign="middle">&#x03C7;<sup>2</sup> =&#x202F;0.001<xref ref-type="table-fn" rid="tfn1"><sup>1</sup></xref></td>
<td align="center" valign="middle">0.98</td>
</tr>
<tr>
<td align="left" valign="middle">Male</td>
<td align="center" valign="middle">151 (85.31)</td>
<td align="center" valign="middle">76 (85.39)</td>
<td align="center" valign="middle">75 (85.23)</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="middle">Female</td>
<td align="center" valign="middle">26 (14.69)</td>
<td align="center" valign="middle">13 (14.60)</td>
<td align="center" valign="middle">13 (14.77)</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="middle">Age, Mean&#x202F;&#x00B1;&#x202F;SD</td>
<td align="center" valign="middle">65.48&#x202F;&#x00B1;&#x202F;9.55</td>
<td align="center" valign="middle">65.62&#x202F;&#x00B1;&#x202F;9.27</td>
<td align="center" valign="middle">65.34&#x202F;&#x00B1;&#x202F;9.88</td>
<td align="center" valign="middle"><italic>t</italic> =&#x202F;0.192<xref ref-type="table-fn" rid="tfn2"><sup>2</sup></xref></td>
<td align="center" valign="middle">0.85</td>
</tr>
<tr>
<td align="left" valign="middle">Hyperlipidemia, <italic>n</italic> (%)</td>
<td/>
<td/>
<td/>
<td align="center" valign="middle">&#x03C7;<sup>2</sup> =&#x202F;0.019<xref ref-type="table-fn" rid="tfn1"><sup>1</sup></xref></td>
<td align="center" valign="middle">0.89</td>
</tr>
<tr>
<td align="left" valign="middle">No</td>
<td align="center" valign="middle">41 (23.16)</td>
<td align="center" valign="middle">21 (23.60)</td>
<td align="center" valign="middle">20 (22.73)</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="middle">Yes</td>
<td align="center" valign="middle">136 (76.84)</td>
<td align="center" valign="middle">68 (76.40)</td>
<td align="center" valign="middle">68 (77.27)</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="middle">Hypertension, <italic>n</italic> (%)</td>
<td/>
<td/>
<td/>
<td align="center" valign="middle">&#x03C7;<sup>2</sup> =&#x202F;0.047<xref ref-type="table-fn" rid="tfn1"><sup>1</sup></xref></td>
<td align="center" valign="middle">0.83</td>
</tr>
<tr>
<td align="left" valign="middle">No</td>
<td align="center" valign="middle">45 (25.42)</td>
<td align="center" valign="middle">22 (24.72)</td>
<td align="center" valign="middle">23 (26.14)</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="middle">Yes</td>
<td align="center" valign="middle">132 (74.58)</td>
<td align="center" valign="middle">67 (75.28)</td>
<td align="center" valign="middle">65 (73.86)</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="middle">Diabetes, <italic>n</italic> (%)</td>
<td/>
<td/>
<td/>
<td align="center" valign="middle">&#x03C7;<sup>2</sup> =&#x202F;0.298<xref ref-type="table-fn" rid="tfn1"><sup>1</sup></xref></td>
<td align="center" valign="middle">0.59</td>
</tr>
<tr>
<td align="left" valign="middle">No</td>
<td align="center" valign="middle">103 (58.19)</td>
<td align="center" valign="middle">50 (56.18)</td>
<td align="center" valign="middle">53 (60.23)</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="middle">Yes</td>
<td align="center" valign="middle">74 (41.81)</td>
<td align="center" valign="middle">39 (43.82)</td>
<td align="center" valign="middle">35 (39.77)</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="middle">Smoking, <italic>n</italic> (%)</td>
<td/>
<td/>
<td/>
<td align="center" valign="middle">&#x03C7;<sup>2</sup> =&#x202F;2.079<xref ref-type="table-fn" rid="tfn1"><sup>1</sup></xref></td>
<td align="center" valign="middle">0.15</td>
</tr>
<tr>
<td align="left" valign="middle">No</td>
<td align="center" valign="middle">106 (59.89)</td>
<td align="center" valign="middle">58 (65.17)</td>
<td align="center" valign="middle">48 (54.55)</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="middle">Yes</td>
<td align="center" valign="middle">71 (40.11)</td>
<td align="center" valign="middle">31 (34.83)</td>
<td align="center" valign="middle">40 (45.46)</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="middle">Alcohol consumption, <italic>n</italic> (%)</td>
<td/>
<td/>
<td/>
<td align="center" valign="middle">&#x03C7;<sup>2</sup> =&#x202F;0.072<xref ref-type="table-fn" rid="tfn1"><sup>1</sup></xref></td>
<td align="center" valign="middle">0.79</td>
</tr>
<tr>
<td align="left" valign="middle">No</td>
<td align="center" valign="middle">119 (67.23)</td>
<td align="center" valign="middle">59 (66.29)</td>
<td align="center" valign="middle">60 (68.18)</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="middle">Yes</td>
<td align="center" valign="middle">58 (32.77)</td>
<td align="center" valign="middle">30 (33.71)</td>
<td align="center" valign="middle">28 (31.82)</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="middle">Coronary heart disease, <italic>n</italic> (%)</td>
<td/>
<td/>
<td/>
<td align="center" valign="middle">&#x03C7;<sup>2</sup> =&#x202F;0.234<xref ref-type="table-fn" rid="tfn1"><sup>1</sup></xref></td>
<td align="center" valign="middle">0.63</td>
</tr>
<tr>
<td align="left" valign="middle">No</td>
<td align="center" valign="middle">134 (75.70)</td>
<td align="center" valign="middle">66 (74.16)</td>
<td align="center" valign="middle">68 (77.27)</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="middle">Yes</td>
<td align="center" valign="middle">43 (24.29)</td>
<td align="center" valign="middle">23 (25.84)</td>
<td align="center" valign="middle">20 (22.73)</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="middle">BMI, Mean&#x202F;&#x00B1;&#x202F;SD</td>
<td align="center" valign="middle">24.94&#x202F;&#x00B1;&#x202F;3.56</td>
<td align="center" valign="middle">24.84&#x202F;&#x00B1;&#x202F;3.23</td>
<td align="center" valign="middle">25.04&#x202F;&#x00B1;&#x202F;3.89</td>
<td align="center" valign="middle"><italic>t</italic> =&#x202F;&#x2212;0.364<xref ref-type="table-fn" rid="tfn2"><sup>2</sup></xref></td>
<td align="center" valign="middle">0.72</td>
</tr>
<tr>
<td align="left" valign="middle">Degree of stenosis %, Mean&#x202F;&#x00B1;&#x202F;SD</td>
<td align="center" valign="middle">82.05&#x202F;&#x00B1;&#x202F;10.94</td>
<td align="center" valign="middle">80.97&#x202F;&#x00B1;&#x202F;11.01</td>
<td align="center" valign="middle">83.15&#x202F;&#x00B1;&#x202F;10.83</td>
<td align="center" valign="middle"><italic>t</italic> =&#x202F;&#x2212;1.329<xref ref-type="table-fn" rid="tfn2"><sup>2</sup></xref></td>
<td align="center" valign="middle">0.19</td>
</tr>
<tr>
<td align="left" valign="middle">Treatment types, <italic>n</italic> (%)</td>
<td/>
<td/>
<td/>
<td align="center" valign="middle">&#x03C7;<sup>2</sup> =&#x202F;0.061<xref ref-type="table-fn" rid="tfn1"><sup>1</sup></xref></td>
<td align="center" valign="middle">0.81</td>
</tr>
<tr>
<td align="left" valign="middle">CAS</td>
<td align="center" valign="middle">162 (91.53)</td>
<td align="center" valign="middle">81 (91.01)</td>
<td align="center" valign="middle">81 (92.05)</td>
<td/>
<td/>
</tr>
<tr>
<td align="left" valign="middle">CEA</td>
<td align="center" valign="middle">15 (8.48)</td>
<td align="center" valign="middle">8 (8.99)</td>
<td align="center" valign="middle">7 (7.96)</td>
<td/>
<td/>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="tfn1"><label>1</label><p>Pearson &#x03C7;<sup>2</sup> test.</p></fn>
<fn id="tfn2"><label>2</label><p>Independent samples t-test.</p></fn>
<p>&#x002A;<italic>p</italic>&#x202F;&#x003C;&#x202F;0.05; &#x002A;&#x002A;<italic>p</italic>&#x202F;&#x003C;&#x202F;0.01.</p>
</table-wrap-foot>
</table-wrap>
</sec>
<sec id="sec9">
<label>3.2</label>
<title>Comparison of pre-and post-treatment variables</title>
<p>Univariate analysis revealed significant differences in the following circadian and physiological parameters between prognosis groups (<xref ref-type="table" rid="tab2">Table 2</xref>).</p>
<table-wrap position="float" id="tab2">
<label>Table 2</label>
<caption>
<p>Univariate Analysis of Prognostic Factors between good (NIHSS&#x202F;&#x2264;&#x202F;2) and poor (NIHSS&#x202F;&#x003E;&#x202F;2) groups.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top">Indicator</th>
<th align="center" valign="top">Good</th>
<th align="center" valign="top">Poor</th>
<th align="center" valign="top">Test statistic (Z/t/&#x03C7;<sup>2</sup>)</th>
<th align="center" valign="top"><italic>p</italic>-value</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="middle">&#x0394;High-Intensity Activity Duration Change (min/week)</td>
<td align="center" valign="middle">32.00 (&#x2212;1.00, 62.00)</td>
<td align="center" valign="middle">39.50 (5.25, 74.00)</td>
<td align="center" valign="middle">&#x2212;1.246</td>
<td align="center" valign="middle">0.213</td>
</tr>
<tr>
<td align="left" valign="middle">&#x0394;High-Intensity Activity Frequency Change</td>
<td align="center" valign="middle">1.00 (0.00, 2.00)</td>
<td align="center" valign="middle">1.00 (0.00, 2.00)</td>
<td align="center" valign="middle">&#x2212;0.855</td>
<td align="center" valign="middle">0.393</td>
</tr>
<tr>
<td align="left" valign="middle">&#x0394;Nighttime Avg Diastolic BP Change (mmHg)&#x002A;&#x002A;</td>
<td align="center" valign="middle">&#x2212;6.00 (&#x2212;8.00, &#x2212;3.00)</td>
<td align="center" valign="middle">&#x2212;1.50 (&#x2212;6.00, 1.00)</td>
<td align="center" valign="middle">&#x2212;5.025</td>
<td align="center" valign="middle">0.000</td>
</tr>
<tr>
<td align="left" valign="middle">&#x0394;Daytime Avg Systolic BP Change (mmHg)</td>
<td align="center" valign="middle">&#x2212;10.00 (&#x2212;13.00, &#x2212;6.50)</td>
<td align="center" valign="middle">&#x2212;9.00 (&#x2212;13.00, &#x2212;7.00)</td>
<td align="center" valign="middle">&#x2212;0.651</td>
<td align="center" valign="middle">0.515</td>
</tr>
<tr>
<td align="left" valign="middle">&#x0394;PSQI Change&#x002A;&#x002A;</td>
<td align="center" valign="middle">&#x2212;1.00 (&#x2212;3.00, &#x2212;1.00)</td>
<td align="center" valign="middle">1.00 (0.00, 2.00)</td>
<td align="center" valign="middle">&#x2212;8.802</td>
<td align="center" valign="middle">0.000</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>&#x002A;<italic>p</italic>&#x202F;&#x003C;&#x202F;0.05; &#x002A;&#x002A;<italic>p</italic>&#x202F;&#x003C;&#x202F;0.01.</p>
</table-wrap-foot>
</table-wrap>
<sec id="sec10">
<label>3.2.1</label>
<title>&#x0394;Nighttime Avg diastolic BP change</title>
<p>Patients with good prognosis had a greater reduction in nighttime diastolic BP (&#x2212;6.00&#x202F;mmHg, IQR: &#x2212;8.00 to-3.00) compared to the poor prognosis group (&#x2212;1.50&#x202F;mmHg, IQR: &#x2212;6.00 to 1.00; <italic>p</italic> &#x003C;&#x202F;0.001).</p>
</sec>
<sec id="sec11">
<label>3.2.2</label>
<title>&#x0394;PSQI change</title>
<p>Good prognosis patients exhibited a median &#x0394;PSQI improvement of &#x2212;1.00 (IQR: &#x2212;3.00 to &#x2212;1.00), while poor prognosis patients showed a worsening of 1.00 (IQR: 0.00 to 2.00; <italic>p</italic> &#x003C;&#x202F;0.001).</p>
</sec>
<sec id="sec12">
<label>3.2.3</label>
<title>Other variables</title>
<p>No significant differences were observed for &#x0394;High-Intensity Activity Duration/Frequency or &#x0394;Daytime Avg Systolic BP Change (<italic>p</italic> &#x003E;&#x202F;0.05).</p>
<p>Multivariate logistic regression identified independent predictors of NIHSS outcomes (<xref ref-type="table" rid="tab3">Table 3</xref>).</p>
<table-wrap position="float" id="tab3">
<label>Table 3</label>
<caption>
<p>Multivariate analysis of prognostic factors.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top" rowspan="2">Variables</th>
<th align="center" valign="top" rowspan="2">B</th>
<th align="center" valign="top" rowspan="2">S.E.</th>
<th align="center" valign="top" rowspan="2">Wald</th>
<th align="center" valign="top" rowspan="2">
<italic>p</italic>
</th>
<th align="center" valign="top" rowspan="2">OR</th>
<th align="center" valign="top" colspan="2">95% CI. OR</th>
</tr>
<tr>
<th align="center" valign="top">Lower limit</th>
<th align="center" valign="top">Upper limit</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="middle">&#x0394;High-Intensity Activity Duration Change (min/week)</td>
<td align="center" valign="middle">0.009</td>
<td align="center" valign="middle">0.006</td>
<td align="center" valign="middle">1.958</td>
<td align="center" valign="middle">0.162</td>
<td align="center" valign="middle">1.009</td>
<td align="center" valign="middle">0.996</td>
<td align="center" valign="middle">1.021</td>
</tr>
<tr>
<td align="left" valign="middle">&#x0394;High-Intensity Activity Frequency Change</td>
<td align="center" valign="middle">0.269</td>
<td align="center" valign="middle">0.169</td>
<td align="center" valign="middle">2.539</td>
<td align="center" valign="middle">0.111</td>
<td align="center" valign="middle">1.309</td>
<td align="center" valign="middle">0.940</td>
<td align="center" valign="middle">1.822</td>
</tr>
<tr>
<td align="left" valign="middle">&#x0394;Night time Avg Diastolic BP Change (mmHg) &#x002A;&#x002A;</td>
<td align="center" valign="middle">0.568</td>
<td align="center" valign="middle">0.111</td>
<td align="center" valign="middle">26.149</td>
<td align="center" valign="middle">0.000</td>
<td align="center" valign="middle">1.764</td>
<td align="center" valign="middle">1.419</td>
<td align="center" valign="middle">2.194</td>
</tr>
<tr>
<td align="left" valign="middle">&#x0394;Daytime Avg Systolic BP Change (mmHg)</td>
<td align="center" valign="middle">0.034</td>
<td align="center" valign="middle">0.050</td>
<td align="center" valign="middle">0.463</td>
<td align="center" valign="middle">0.496</td>
<td align="center" valign="middle">1.035</td>
<td align="center" valign="middle">0.938</td>
<td align="center" valign="middle">1.142</td>
</tr>
<tr>
<td align="left" valign="middle">&#x0394;PSQI Change&#x002A;&#x002A;</td>
<td align="center" valign="middle">2.002</td>
<td align="center" valign="middle">0.334</td>
<td align="center" valign="middle">35.862</td>
<td align="center" valign="middle">0.000</td>
<td align="center" valign="middle">7.403</td>
<td align="center" valign="middle">3.845</td>
<td align="center" valign="middle">14.256</td>
</tr>
<tr>
<td align="left" valign="middle">Constant</td>
<td align="center" valign="middle">2.730</td>
<td align="center" valign="middle">0.826</td>
<td align="center" valign="middle">10.920</td>
<td align="center" valign="middle">0.001</td>
<td align="center" valign="middle">15.329</td>
<td/>
<td/>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>&#x002A;<italic>p</italic>&#x202F;&#x003C;&#x202F;0.05; &#x002A;&#x002A;<italic>p</italic>&#x202F;&#x003C;&#x202F;0.01.</p>
</table-wrap-foot>
</table-wrap>
</sec>
<sec id="sec13">
<label>3.2.4</label>
<title>&#x0394;PSQI change</title>
<p>An improvement in sleep quality was strongly associated with better prognosis (OR&#x202F;=&#x202F;7.403; 95% CI: 3.845&#x2013;14.256; <italic>p</italic> &#x003C;&#x202F;0.001).</p>
</sec>
<sec id="sec14">
<label>3.2.5</label>
<title>&#x0394;Nighttime Avg diastolic BP change</title>
<p>Greater reductions in nighttime diastolic BP were significantly predictive of favorable outcomes (OR&#x202F;=&#x202F;1.764; 95% CI: 1.419&#x2013;2.194; <italic>p</italic> &#x003C;&#x202F;0.001).</p>
</sec>
<sec id="sec15">
<label>3.2.6</label>
<title>Coronary heart disease</title>
<p>Presence of coronary heart disease was associated with poorer outcomes (OR&#x202F;=&#x202F;0.863; 95% CI: 0.773&#x2013;0.963; <italic>p</italic> =&#x202F;0.009).</p>
</sec>
<sec id="sec16">
<label>3.2.7</label>
<title>Pre-treatment PSQI total</title>
<p>Higher pre-treatment PSQI scores were weakly associated with worse prognosis (OR&#x202F;=&#x202F;0.983; 95% CI: 0.968&#x2013;0.999; <italic>p</italic> =&#x202F;0.035).</p>
</sec>
</sec>
<sec id="sec17">
<label>3.3</label>
<title>Stepwise regression analysis</title>
<p>Stepwise regression analysis was performed to identify significant predictors of NIHSS outcomes, incorporating changes in PSQI and blood pressure as well as the presence of coronary heart disease (<xref ref-type="table" rid="tab4">Table 4</xref>).</p>
<table-wrap position="float" id="tab4">
<label>Table 4</label>
<caption>
<p>Stepwise regression analysis of factors influencing NIHSS outcomes.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th rowspan="2"/>
<th align="center" valign="top" rowspan="2">Coefficient (B)</th>
<th align="center" valign="top" rowspan="2">OR</th>
<th align="center" valign="top" rowspan="2">95% CI</th>
<th align="center" valign="top" rowspan="2"><italic>p</italic>-value</th>
<th align="center" valign="top" colspan="2">Collinearity diagnostics</th>
</tr>
<tr>
<th align="center" valign="top">VIF</th>
<th align="center" valign="top">Tolerance</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="middle">&#x0394;Night time Avg Diastolic BP Change (mmHg)</td>
<td align="center" valign="middle">0.043&#x002A;&#x002A;</td>
<td align="center" valign="middle">1.044</td>
<td align="center" valign="middle">1.034&#x202F;~&#x202F;1.054</td>
<td align="center" valign="middle">0.000&#x002A;&#x002A;</td>
<td align="center" valign="middle">1.011</td>
<td align="center" valign="middle">0.989</td>
</tr>
<tr>
<td align="left" valign="middle">&#x0394;PSQI Change</td>
<td align="center" valign="middle">0.189&#x002A;&#x002A;</td>
<td align="center" valign="middle">1.208</td>
<td align="center" valign="middle">1.176&#x202F;~&#x202F;1.240</td>
<td align="center" valign="middle">0.000&#x002A;&#x002A;</td>
<td align="center" valign="middle">1.006</td>
<td align="center" valign="middle">0.994</td>
</tr>
<tr>
<td align="left" valign="middle">Coronary Heart Disease</td>
<td align="center" valign="middle">&#x2212;0.147&#x002A;&#x002A;</td>
<td align="center" valign="middle">0.863</td>
<td align="center" valign="middle">0.773&#x202F;~&#x202F;0.963</td>
<td align="center" valign="middle">0.009&#x002A;&#x002A;</td>
<td align="center" valign="middle">1.017</td>
<td align="center" valign="middle">0.984</td>
</tr>
<tr>
<td align="left" valign="middle">Pre-treatment PSQI Total</td>
<td align="center" valign="middle">&#x2212;0.017&#x002A;</td>
<td align="center" valign="middle">0.983</td>
<td align="center" valign="middle">0.968&#x202F;~&#x202F;0.999</td>
<td align="center" valign="middle">0.035&#x002A;</td>
<td align="center" valign="middle">1.004</td>
<td align="center" valign="middle">0.996</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>&#x002A;<italic>p</italic>&#x202F;&#x003C;&#x202F;0.05; &#x002A;&#x002A;<italic>p</italic>&#x202F;&#x003C;&#x202F;0.01.</p>
</table-wrap-foot>
</table-wrap>
<p>Change in PSQI (Post-treatment - Pre-treatment): An increase in PSQI was associated with a 20.8% higher likelihood of a poor NIHSS outcome (OR&#x202F;=&#x202F;1.208, <italic>p</italic>&#x202F;&#x003C;&#x202F;0.001).</p>
<p>Change in Nighttime Diastolic BP: A 1&#x202F;mmHg increase in nighttime diastolic BP post-treatment was associated with a 4.4% higher likelihood of a poor NIHSS outcome (OR&#x202F;=&#x202F;1.044, <italic>p</italic>&#x202F;&#x003C;&#x202F;0.001).</p>
<p>Presence of Coronary Heart Disease: Coronary heart disease was associated with a 13.7% lower likelihood of a good NIHSS outcome (OR&#x202F;=&#x202F;0.863, <italic>p</italic>&#x202F;=&#x202F;0.009).</p>
<p>Pre-treatment PSQI Total: Higher baseline PSQI scores were associated with a slightly lower likelihood of a poor outcome (OR&#x202F;=&#x202F;0.983, <italic>p</italic>&#x202F;=&#x202F;0.035), reflecting the complex relationship between sleep quality and stroke recovery.</p>
</sec>
</sec>
<sec sec-type="discussion" id="sec18">
<label>4</label>
<title>Discussion</title>
<p>Circadian rhythm, controlled by the biological clock, is essential for maintaining normal physiological functions, regulating processes like the sleep&#x2013;wake cycle, hormone secretion, and cardiovascular function (<xref ref-type="bibr" rid="ref18">18</xref>). In healthy individuals, these functions follow a 24-h cycle, helping the body adapt to environmental changes (<xref ref-type="bibr" rid="ref19">19</xref>). However, in disease states, circadian rhythms may be disrupted, leading to physiological dysfunction, and subsequently affecting the onset, progression, and prognosis of diseases (<xref ref-type="bibr" rid="ref20">20</xref>). Stroke patients often exhibit circadian rhythm disorders, such as sleep disturbances, increased blood pressure variability, and changes in heart rate variability (<xref ref-type="bibr" rid="ref21">21</xref>). These changes may result from factors like central nervous system damage, inflammatory responses, stress responses, and lifestyle changes (<xref ref-type="bibr" rid="ref22">22</xref>). For example, acute stroke can induce neuroinflammation and oxidative stress, affecting the hypothalamic&#x2013;pituitary&#x2013;adrenal axis function, leading to circadian rhythm disturbances (<xref ref-type="bibr" rid="ref23">23</xref>). Additionally, environmental changes during hospitalization, such as light exposure and activity patterns, can also disrupt the patient&#x2019;s biological clock (<xref ref-type="bibr" rid="ref24">24</xref>). These disruptions may further affect recovery, as the circadian rhythm plays a crucial role in regulating various physiological processes. This study systematically evaluated circadian rhythm changes before and after CEA or CAS and their impact on patient prognosis. Specific objectives included comparing changes in sleep quality (PSQI) before and after treatment to assess its impact on recovery and prognosis; analyzing circadian blood pressure variability (SBP and DBP) to understand the importance of BP control in stroke treatment; evaluating neurological recovery (NIHSS scores) to explore its clinical implications; and examining physical activity levels (IPAQ scores) to explore their role in recovery. Through these objectives, the study aims to provide insights for clinicians in developing personalized treatment and rehabilitation plans based on circadian rhythm characteristics, ultimately improving stroke prognosis and quality of life. The study results deepen our understanding of physiological changes in stroke patients and provide evidence for personalized treatment and rehabilitation strategies. This research holds significant innovation and practical value in circadian rhythm and disease recovery studies. Our findings emphasize that specific disruptions in circadian rhythms, particularly changes in sleep quality (PSQI) and nighttime diastolic blood pressure, are significant predictors of stroke outcomes and patient recovery, as reflected in NIHSS scores.</p>
<sec id="sec19">
<label>4.1</label>
<title>Impact of sleep quality on stroke recovery</title>
<p>The results demonstrate a clear relationship between sleep quality and stroke outcomes, as measured by the National Institutes of Health Stroke Scale (NIHSS). Poor sleep quality post-intervention was associated with worse neurological outcomes, consistent with existing literature linking sleep disturbances to impaired functional recovery following a stroke (<xref ref-type="bibr" rid="ref25">25</xref>, <xref ref-type="bibr" rid="ref26">26</xref>). This observation underscores the importance of incorporating sleep quality improvement into stroke management, as disruptions in circadian rhythms&#x2014;particularly in blood pressure variability and sleep&#x2013;wake cycles&#x2014;are closely linked to poor prognosis in stroke patients (<xref ref-type="bibr" rid="ref12">12</xref>, <xref ref-type="bibr" rid="ref25">25</xref>). Interestingly, higher baseline PSQI scores were unexpectedly associated with a slightly lower likelihood of poor outcomes, which may suggest the presence of adaptive compensatory mechanisms. However, this counterintuitive finding suggests that baseline sleep disturbances may trigger compensatory mechanisms that improve post-treatment recovery, warranting further investigation (<xref ref-type="bibr" rid="ref27">27</xref>).</p>
</sec>
<sec id="sec20">
<label>4.2</label>
<title>Role of blood pressure variability and prognosis</title>
<p>The focus on daytime SBP and nighttime DBP in our analysis aligns with their respective roles in cardiovascular function and circadian regulation. Daytime SBP reflects the cardiovascular load during active periods, which can impact vascular recovery following interventions. In contrast, nighttime DBP serves as a marker of circadian rhythm stability, with abnormalities such as non-dipping patterns being linked to poor neurological outcomes. These findings are consistent with previous research highlighting the prognostic value of daytime SBP and nighttime DBP in stroke recovery (<xref ref-type="bibr" rid="ref17">17</xref>). Circadian blood pressure variability, particularly nighttime diastolic blood pressure, has emerged as another crucial factor influencing stroke recovery. Our findings demonstrated that elevated nighttime diastolic blood pressure post-treatment was significantly associated with worse neurological outcomes. This is consistent with previous research showing that abnormal blood pressure patterns, especially during sleep, can increase the risk of cardiovascular events and impede stroke recovery (<xref ref-type="bibr" rid="ref28">28</xref>). The autonomic nervous system plays a key role in regulating circadian blood pressure rhythms, and disruptions in this system, common after a stroke, may lead to fluctuations in blood pressure (<xref ref-type="bibr" rid="ref29">29</xref>). Such variability can further damage cerebral vasculature, increase the risk of recurrent strokes, and hinder brain repair mechanisms (<xref ref-type="bibr" rid="ref30">30</xref>). Our study emphasizes the need for continuous monitoring and management of blood pressure during both the daytime and nighttime periods in stroke patients. Antihypertensive treatment protocols that focus on restoring normal circadian blood pressure rhythms could improve long-term outcomes (<xref ref-type="bibr" rid="ref31">31</xref>).</p>
</sec>
<sec id="sec21">
<label>4.3</label>
<title>Physical activity and rehabilitation</title>
<p>The increase in high-intensity physical activity post-treatment, as measured by the International Physical Activity Questionnaire (IPAQ), was associated with better neurological outcomes, particularly in patients who showed greater improvement in NIHSS scores. Physical activity has been shown to promote neuroplasticity, enhance cardiovascular health, and improve overall functional recovery in stroke patients (<xref ref-type="bibr" rid="ref32">32</xref>). Our results align with the growing body of evidence supporting the role of exercise in stroke rehabilitation.</p>
<p>The beneficial effects of physical activity on stroke recovery may be mediated through multiple mechanisms, including improved cerebral perfusion, reduced inflammation, and enhanced synaptic plasticity (<xref ref-type="bibr" rid="ref3">3</xref>). Rehabilitation programs should prioritize the integration of structured physical activity, tailored to the individual patient&#x2019;s capacity and recovery stage, to maximize neurological recovery. Our study suggests that encouraging regular, high-intensity exercise, when clinically appropriate, could significantly improve patient outcomes.</p>
</sec>
<sec id="sec22">
<label>4.4</label>
<title>Impact of coronary heart disease on stroke outcomes</title>
<p>Our study also identified the presence of coronary heart disease (CHD) as a significant factor influencing stroke prognosis. Patients with CHD had a 13.7% lower likelihood of achieving a good NIHSS outcome, emphasizing the interplay between cardiovascular comorbidities and stroke recovery. CHD is known to exacerbate the risk of ischemic events and can lead to poorer outcomes due to the compounded stress on the cardiovascular system during recovery (<xref ref-type="bibr" rid="ref33">33</xref>). This finding underscores the need for integrated care approaches that address both cerebrovascular and cardiovascular health to optimize patient outcomes post-CEA or CAS.</p>
</sec>
<sec id="sec23">
<label>4.5</label>
<title>Clinical implications</title>
<p>The findings of this study have important clinical implications. First, they highlight the critical role of circadian rhythms, particularly sleep quality and blood pressure variability, in determining stroke recovery outcomes. Clinicians should routinely assess and monitor circadian rhythm disruptions in stroke patients, both before and after surgical interventions such as CEA or CAS. Addressing circadian disturbances through early interventions could potentially optimize recovery and improve the overall quality of life for stroke survivors.</p>
<p>Second, the significant impact of post-treatment blood pressure variability underscores the importance of personalized blood pressure management strategies. Clinicians should consider using ambulatory blood pressure monitoring to detect abnormal nocturnal blood pressure patterns and adjust antihypertensive treatments accordingly. Furthermore, this study highlights the potential value of incorporating physical activity into rehabilitation protocols as a critical component of the recovery process.</p>
</sec>
<sec id="sec24">
<label>4.6</label>
<title>Limitations and future directions</title>
<p>Despite the significant findings of this study, several limitations should be acknowledged. First, while the analysis included factors such as BMI, smoking status, and comorbidities, these factors did not show significant effects in this sample. However, these variables may play a crucial role in different populations or under alternative treatment protocols. Future research should include larger sample sizes or adopt different study designs to further explore the complex interactions between these variables and stroke recovery outcomes.</p>
<p>Second, the sample size in the current study may not be sufficient to generalize the findings to all stroke patients with carotid artery stenosis undergoing treatment. The small sample size limits the generalizability of the results, and future studies should increase the sample size to enhance the reliability and external validity of the findings.</p>
<p>Finally, potential confounding factors, such as variations in patient adherence to treatment protocols, differences in hospital environments, and individual lifestyle factors, were not adequately controlled for in this study, which may introduce bias into the results. Additionally, some outcomes relied on self-reported data, particularly in the assessment of sleep quality and physical activity levels, which may introduce reporting bias. Future studies should aim to rigorously control for these variables to more accurately assess the impact of circadian rhythm changes on patient outcomes.</p>
</sec>
</sec>
<sec sec-type="conclusions" id="sec25">
<label>5</label>
<title>Conclusion</title>
<p>In conclusion, this study highlights the critical role of circadian rhythm in the recovery of stroke patients undergoing CEA or CAS. The significant associations between sleep quality, blood pressure stability, coronary heart disease, and neurological outcomes provide a compelling case for integrating circadian rhythm management into stroke treatment protocols. These findings pave the way for more personalized and effective rehabilitation strategies, ultimately improving patient outcomes and quality of life.</p>
</sec>
</body>
<back>
<sec sec-type="data-availability" id="sec26">
<title>Data availability statement</title>
<p>The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.</p>
</sec>
<sec sec-type="ethics-statement" id="sec27">
<title>Ethics statement</title>
<p>The studies involving humans were approved by the Institutional Ethics Committee at the PLA Rocket Force Characteristic Medical Center approval (X2017008). The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.</p>
</sec>
<sec sec-type="author-contributions" id="sec28">
<title>Author contributions</title>
<p>YQ: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Resources, Software, Supervision, Validation, Visualization, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing. ZW: Conceptualization, Data curation, Formal analysis, Methodology, Project administration, Writing &#x2013; review &#x0026; editing. TZ: Investigation, Software, Supervision, Validation, Visualization, Writing &#x2013; review &#x0026; editing. YS: Conceptualization, Data curation, Investigation, Project administration, Writing &#x2013; original draft. XZ: Project administration, Writing &#x2013; review &#x0026; editing. XJ: Investigation, Project administration, Resources, Visualization, Writing &#x2013; review &#x0026; editing. A-fL: Data curation, Formal analysis, Resources, Writing &#x2013; review &#x0026; editing. WJ: Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing.</p>
</sec>
<sec sec-type="funding-information" id="sec29">
<title>Funding</title>
<p>The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.</p>
</sec>
<sec sec-type="COI-statement" id="sec30">
<title>Conflict of interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec sec-type="disclaimer" id="sec31">
<title>Publisher&#x2019;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
<sec sec-type="supplementary-material" id="sec32">
<title>Supplementary material</title>
<p>The Supplementary material for this article can be found online at: <ext-link xlink:href="https://www.frontiersin.org/articles/10.3389/fneur.2024.1501316/full#supplementary-material" ext-link-type="uri">https://www.frontiersin.org/articles/10.3389/fneur.2024.1501316/full#supplementary-material</ext-link></p>
<supplementary-material xlink:href="Table_1.docx" id="SM1" mimetype="application/vnd.openxmlformats-officedocument.wordprocessingml.document" xmlns:xlink="http://www.w3.org/1999/xlink"/>
</sec>
<ref-list>
<title>References</title>
<ref id="ref1"><label>1.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Barnett</surname> <given-names>HJM</given-names></name> <name><surname>Taylor</surname> <given-names>DW</given-names></name> <name><surname>Haynes</surname> <given-names>RB</given-names></name> <name><surname>Sackett</surname> <given-names>DL</given-names></name> <name><surname>Peerless</surname> <given-names>SJ</given-names></name> <name><surname>Ferguson</surname> <given-names>GG</given-names></name> <etal/></person-group>. <article-title>Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis</article-title>. <source>N Engl J Med</source>. (<year>1991</year>) <volume>325</volume>:<fpage>445</fpage>&#x2013;<lpage>53</lpage>. PMID: <pub-id pub-id-type="pmid">1852179</pub-id></citation></ref>
<ref id="ref2"><label>2.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Brott</surname> <given-names>TG</given-names></name> <name><surname>Hobson</surname> <given-names>RW</given-names> <suffix>2nd</suffix></name> <name><surname>Howard</surname> <given-names>G</given-names></name> <name><surname>Roubin</surname> <given-names>GS</given-names></name> <name><surname>Clark</surname> <given-names>WM</given-names></name> <name><surname>Brooks</surname> <given-names>W</given-names></name> <etal/></person-group>. <article-title>Stenting versus endarterectomy for treatment of carotid-artery stenosis</article-title>. <source>N Engl J Med</source>. (<year>2010</year>) <volume>363</volume>:<fpage>11</fpage>&#x2013;<lpage>23</lpage>. doi: <pub-id pub-id-type="doi">10.1056/NEJMoa0912321</pub-id>, PMID: <pub-id pub-id-type="pmid">20505173</pub-id></citation></ref>
<ref id="ref3"><label>3.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Takahashi</surname> <given-names>JS</given-names></name> <name><surname>Hong</surname> <given-names>HK</given-names></name> <name><surname>Ko</surname> <given-names>CH</given-names></name> <name><surname>McDearmon</surname> <given-names>EL</given-names></name></person-group>. <article-title>The genetics of mammalian circadian order and disorder: implications for physiology and disease</article-title>. <source>Nat Rev Genet</source>. (<year>2008</year>) <volume>9</volume>:<fpage>764</fpage>&#x2013;<lpage>75</lpage>. doi: <pub-id pub-id-type="doi">10.1038/nrg2430</pub-id></citation></ref>
<ref id="ref4"><label>4.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Scheer</surname> <given-names>FA</given-names></name> <name><surname>Hu</surname> <given-names>K</given-names></name> <name><surname>Evoniuk</surname> <given-names>H</given-names></name> <name><surname>Kelly</surname> <given-names>EE</given-names></name> <name><surname>Malhotra</surname> <given-names>A</given-names></name> <name><surname>Hilton</surname> <given-names>MF</given-names></name> <etal/></person-group>. <article-title>Impact of the human circadian system, exercise, and their interaction on cardiovascular function</article-title>. <source>Proc Natl Acad Sci USA</source>. (<year>2010</year>) <volume>107</volume>:<fpage>20541</fpage>&#x2013;<lpage>6</lpage>. doi: <pub-id pub-id-type="doi">10.1073/pnas.1006749107</pub-id>, PMID: <pub-id pub-id-type="pmid">21059915</pub-id></citation></ref>
<ref id="ref5"><label>5.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Fox</surname> <given-names>KM</given-names></name> <name><surname>Mulcahy</surname> <given-names>DA</given-names></name></person-group>. <article-title>Circadian rhythms in cardiovascular function</article-title>. <source>Postgrad Med J</source>. (<year>1991</year>) <volume>67</volume>:<fpage>S33</fpage>&#x2013;<lpage>6</lpage>.</citation></ref>
<ref id="ref6"><label>6.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Zielinski</surname> <given-names>MR</given-names></name> <name><surname>Gibbons</surname> <given-names>AJ</given-names></name></person-group>. <article-title>Neuroinflammation, sleep, and circadian rhythms</article-title>. <source>Front Cell Infect Microbiol</source>. (<year>2022</year>) <volume>12</volume>:<fpage>853096</fpage>. doi: <pub-id pub-id-type="doi">10.3389/fcimb.2022.853096</pub-id>, PMID: <pub-id pub-id-type="pmid">35392608</pub-id></citation></ref>
<ref id="ref7"><label>7.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Zhang</surname> <given-names>J</given-names></name> <name><surname>Du</surname> <given-names>L</given-names></name> <name><surname>Li</surname> <given-names>J</given-names></name> <name><surname>Li</surname> <given-names>R</given-names></name> <name><surname>Jin</surname> <given-names>X</given-names></name> <name><surname>Ren</surname> <given-names>J</given-names></name> <etal/></person-group>. <article-title>Association between circadian variation of heart rate and mortality among critically ill patients: a retrospective cohort study</article-title>. <source>BMC Anesthesiol</source>. (<year>2022</year>) <volume>22</volume>:<fpage>45</fpage>. doi: <pub-id pub-id-type="doi">10.1186/s12871-022-01586-9</pub-id>, PMID: <pub-id pub-id-type="pmid">35151270</pub-id></citation></ref>
<ref id="ref8"><label>8.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Sundararajan</surname> <given-names>K</given-names></name> <name><surname>Flabouris</surname> <given-names>A</given-names></name> <name><surname>Thompson</surname> <given-names>C</given-names></name></person-group>. <article-title>Diurnal variation in the performance of rapid response systems: the role of critical care services-a review article</article-title>. <source>J Intensive Care</source>. (<year>2016</year>) <volume>4</volume>:<fpage>15</fpage>. doi: <pub-id pub-id-type="doi">10.1186/s40560-016-0136-5</pub-id>, PMID: <pub-id pub-id-type="pmid">26913199</pub-id></citation></ref>
<ref id="ref9"><label>9.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Gallerani</surname> <given-names>M</given-names></name> <name><surname>Portaluppi</surname> <given-names>F</given-names></name> <name><surname>Maida</surname> <given-names>G</given-names></name> <name><surname>Chieregato</surname> <given-names>A</given-names></name> <name><surname>Calzolari</surname> <given-names>F</given-names></name> <name><surname>Trapella</surname> <given-names>G</given-names></name> <etal/></person-group>. <article-title>Circadian and circannual rhythmicity in the occurrence of subarachnoid hemorrhage</article-title>. <source>Stroke</source>. (<year>1996</year>) <volume>27</volume>:<fpage>1793</fpage>&#x2013;<lpage>7</lpage>. doi: <pub-id pub-id-type="doi">10.1161/01.STR.27.10.1793</pub-id>, PMID: <pub-id pub-id-type="pmid">8841332</pub-id></citation></ref>
<ref id="ref10"><label>10.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Adams</surname> <given-names>HP</given-names> <suffix>Jr</suffix></name> <name><surname>Bendixen</surname> <given-names>BH</given-names></name> <name><surname>Kappelle</surname> <given-names>LJ</given-names></name> <name><surname>Biller</surname> <given-names>J</given-names></name> <name><surname>Love</surname> <given-names>BB</given-names></name> <name><surname>Gordon</surname> <given-names>DL</given-names></name> <etal/></person-group>. <article-title>Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of org 10172 in acute stroke treatment</article-title>. <source>Stroke</source>. (<year>1993</year>) <volume>24</volume>:<fpage>35</fpage>&#x2013;<lpage>41</lpage>. doi: <pub-id pub-id-type="doi">10.1161/01.STR.24.1.35</pub-id>, PMID: <pub-id pub-id-type="pmid">7678184</pub-id></citation></ref>
<ref id="ref11"><label>11.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Morris</surname> <given-names>CJ</given-names></name> <name><surname>Purvis</surname> <given-names>TE</given-names></name> <name><surname>Hu</surname> <given-names>K</given-names></name> <name><surname>Scheer</surname> <given-names>FA</given-names></name></person-group>. <article-title>Circadian misalignment increases cardiovascular disease risk factors in humans</article-title>. <source>Proc Natl Acad Sci USA</source>. (<year>2016</year>) <volume>113</volume>:<fpage>E1402</fpage>&#x2013;<lpage>11</lpage>. doi: <pub-id pub-id-type="doi">10.1073/pnas.1516953113</pub-id>, PMID: <pub-id pub-id-type="pmid">26858430</pub-id></citation></ref>
<ref id="ref12"><label>12.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Hermida</surname> <given-names>RC</given-names></name> <name><surname>Ayala</surname> <given-names>DE</given-names></name> <name><surname>Moj&#x00F3;n</surname> <given-names>A</given-names></name> <name><surname>Fern&#x00E1;ndez</surname> <given-names>JR</given-names></name></person-group>. <article-title>Influence of circadian time of hypertension treatment on cardiovascular risk: results of the MAPEC study</article-title>. <source>Chronobiol Int</source>. (<year>2010</year>) <volume>27</volume>:<fpage>1629</fpage>&#x2013;<lpage>51</lpage>. doi: <pub-id pub-id-type="doi">10.3109/07420528.2010.510230</pub-id>, PMID: <pub-id pub-id-type="pmid">20854139</pub-id></citation></ref>
<ref id="ref13"><label>13.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Elliott</surname> <given-names>WJ</given-names></name></person-group>. <article-title>Circadian variation in the timing of stroke onset: a meta-analysis</article-title>. <source>Stroke</source>. (<year>1998</year>) <volume>29</volume>:<fpage>992</fpage>&#x2013;<lpage>6</lpage>. doi: <pub-id pub-id-type="doi">10.1161/01.STR.29.5.992</pub-id>, PMID: <pub-id pub-id-type="pmid">9596248</pub-id></citation></ref>
<ref id="ref14"><label>14.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Shea</surname> <given-names>SA</given-names></name> <name><surname>Hilton</surname> <given-names>MF</given-names></name> <name><surname>Hu</surname> <given-names>K</given-names></name> <name><surname>Scheer</surname> <given-names>FA</given-names></name></person-group>. <article-title>Existence of an endogenous circadian blood pressure rhythm in humans that peaks in the evening</article-title>. <source>Circ Res</source>. (<year>2011</year>) <volume>108</volume>:<fpage>980</fpage>&#x2013;<lpage>4</lpage>. doi: <pub-id pub-id-type="doi">10.1161/CIRCRESAHA.110.233668</pub-id>, PMID: <pub-id pub-id-type="pmid">21474818</pub-id></citation></ref>
<ref id="ref15"><label>15.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Qu</surname> <given-names>F</given-names></name> <name><surname>Luo</surname> <given-names>Y</given-names></name> <name><surname>Peng</surname> <given-names>Y</given-names></name> <name><surname>Yu</surname> <given-names>H</given-names></name> <name><surname>Sun</surname> <given-names>L</given-names></name> <name><surname>Liu</surname> <given-names>S</given-names></name> <etal/></person-group>. <article-title>Construction and validation of a prognostic nutritional index-based nomogram for predicting pathological complete response in breast cancer: a two-center study of 1,170 patients</article-title>. <source>Front Immunol</source>. (<year>2023</year>) <volume>14</volume>:<fpage>1335546</fpage>. doi: <pub-id pub-id-type="doi">10.3389/fimmu.2023.1335546</pub-id></citation></ref>
<ref id="ref16"><label>16.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Adams</surname> <given-names>HP</given-names> <suffix>Jr</suffix></name> <name><surname>Davis</surname> <given-names>PH</given-names></name> <name><surname>Leira</surname> <given-names>EC</given-names></name> <name><surname>Chang</surname> <given-names>KC</given-names></name> <name><surname>Bendixen</surname> <given-names>BH</given-names></name> <name><surname>Clarke</surname> <given-names>WR</given-names></name> <etal/></person-group>. <article-title>Baseline NIH stroke scale score strongly predicts outcome after stroke: a report of the trial of org 10172 in acute stroke treatment (TOAST)</article-title>. <source>Neurology</source>. (<year>1999</year>) <volume>53</volume>:<fpage>126</fpage>&#x2013;<lpage>31</lpage>. doi: <pub-id pub-id-type="doi">10.1212/WNL.53.1.126</pub-id>, PMID: <pub-id pub-id-type="pmid">10408548</pub-id></citation></ref>
<ref id="ref17"><label>17.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Weber</surname> <given-names>MA</given-names></name></person-group>. <article-title>Blood pressure variability and cardiovascular prognosis: implications for clinical practice</article-title>. <source>Eur Heart J</source>. (<year>2017</year>) <volume>38</volume>:<fpage>2823</fpage>&#x2013;<lpage>6</lpage>. doi: <pub-id pub-id-type="doi">10.1093/eurheartj/ehx322</pub-id>, PMID: <pub-id pub-id-type="pmid">28982228</pub-id></citation></ref>
<ref id="ref18"><label>18.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Hermida</surname> <given-names>RC</given-names></name> <name><surname>Ayala</surname> <given-names>DE</given-names></name> <name><surname>Moj&#x00F3;n</surname> <given-names>A</given-names></name> <name><surname>Fern&#x00E1;ndez</surname> <given-names>JR</given-names></name></person-group>. <article-title>Bedtime dosing of antihypertensive medications reduces cardiovascular risk in CKD</article-title>. <source>J Am Soc Nephrol</source>. (<year>2011</year>) <volume>22</volume>:<fpage>2313</fpage>&#x2013;<lpage>21</lpage>. doi: <pub-id pub-id-type="doi">10.1681/ASN.2011040361</pub-id>, PMID: <pub-id pub-id-type="pmid">22025630</pub-id></citation></ref>
<ref id="ref19"><label>19.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Czeisler</surname> <given-names>CA</given-names></name> <name><surname>Duffy</surname> <given-names>JF</given-names></name> <name><surname>Shanahan</surname> <given-names>TL</given-names></name> <name><surname>Brown</surname> <given-names>EN</given-names></name> <name><surname>Mitchell</surname> <given-names>JF</given-names></name> <name><surname>Rimmer</surname> <given-names>DW</given-names></name> <etal/></person-group>. <article-title>Stability, precision, and near-24-hour period of the human circadian pacemaker</article-title>. <source>Science</source>. (<year>1999</year>) <volume>284</volume>:<fpage>2177</fpage>&#x2013;<lpage>81</lpage>. doi: <pub-id pub-id-type="doi">10.1126/science.284.5423.2177</pub-id>, PMID: <pub-id pub-id-type="pmid">10381883</pub-id></citation></ref>
<ref id="ref20"><label>20.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Duffy</surname> <given-names>JF</given-names></name> <name><surname>Czeisler</surname> <given-names>CA</given-names></name></person-group>. <article-title>Effect of light on human circadian physiology</article-title>. <source>Sleep Med Clin</source>. (<year>2009</year>) <volume>4</volume>:<fpage>165</fpage>&#x2013;<lpage>77</lpage>. doi: <pub-id pub-id-type="doi">10.1016/j.jsmc.2009.01.004</pub-id>, PMID: <pub-id pub-id-type="pmid">20161220</pub-id></citation></ref>
<ref id="ref21"><label>21.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>B&#x00F8;ggild</surname> <given-names>H</given-names></name> <name><surname>Knutsson</surname> <given-names>A</given-names></name></person-group>. <article-title>Shift work, risk factors and cardiovascular disease</article-title>. <source>Scand J Work Environ Health</source>. (<year>1999</year>) <volume>25</volume>:<fpage>85</fpage>&#x2013;<lpage>99</lpage>. doi: <pub-id pub-id-type="doi">10.5271/sjweh.410</pub-id></citation></ref>
<ref id="ref22"><label>22.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Manfredini</surname> <given-names>R</given-names></name> <name><surname>Boari</surname> <given-names>B</given-names></name> <name><surname>Smolensky</surname> <given-names>MH</given-names></name> <name><surname>Salmi</surname> <given-names>R</given-names></name> <name><surname>La Cecilia</surname> <given-names>O</given-names></name> <name><surname>Maria Malagoni</surname> <given-names>A</given-names></name> <etal/></person-group>. <article-title>Circadian variation in stroke onset: identical temporal pattern in ischemic and hemorrhagic events</article-title>. <source>Chronobiol Int</source>. (<year>2005</year>) <volume>22</volume>:<fpage>417</fpage>&#x2013;<lpage>53</lpage>. doi: <pub-id pub-id-type="doi">10.1081/CBI-200062927</pub-id>, PMID: <pub-id pub-id-type="pmid">16076646</pub-id></citation></ref>
<ref id="ref23"><label>23.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Kasim</surname> <given-names>HH</given-names></name> <name><surname>Masri</surname> <given-names>MA</given-names></name> <name><surname>Noh</surname> <given-names>NA</given-names></name> <name><surname>Mokhtar</surname> <given-names>A</given-names></name> <name><surname>Mokhtar</surname> <given-names>RH</given-names></name></person-group>. <article-title>Clinical implications of blood pressure variability (BPV) in pregnancies: a review</article-title>. <source>Horm Mol Biol Clin Investig</source>. (<year>2019</year>) <volume>39</volume>:<fpage>20180060</fpage>. doi: <pub-id pub-id-type="doi">10.1515/hmbci-2018-0060</pub-id></citation></ref>
<ref id="ref24"><label>24.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Banks</surname> <given-names>S</given-names></name> <name><surname>Dinges</surname> <given-names>DF</given-names></name></person-group>. <article-title>Behavioral and physiological consequences of sleep restriction</article-title>. <source>J Clin Sleep Med</source>. (<year>2007</year>) <volume>3</volume>:<fpage>519</fpage>&#x2013;<lpage>28</lpage>. doi: <pub-id pub-id-type="doi">10.5664/jcsm.26918</pub-id></citation></ref>
<ref id="ref25"><label>25.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Fulk</surname> <given-names>GD</given-names></name> <name><surname>Boyne</surname> <given-names>P</given-names></name> <name><surname>Hauger</surname> <given-names>M</given-names></name> <name><surname>Ghosh</surname> <given-names>R</given-names></name> <name><surname>Romano</surname> <given-names>S</given-names></name> <name><surname>Thomas</surname> <given-names>J</given-names></name> <etal/></person-group>. <article-title>The impact of sleep disorders on functional recovery and participation following stroke: a systematic review and Meta-analysis</article-title>. <source>Neurorehabil Neural Repair</source>. (<year>2020</year>) <volume>34</volume>:<fpage>1050</fpage>&#x2013;<lpage>61</lpage>. doi: <pub-id pub-id-type="doi">10.1177/1545968320962501</pub-id>, PMID: <pub-id pub-id-type="pmid">33153378</pub-id></citation></ref>
<ref id="ref26"><label>26.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Xie</surname> <given-names>JC</given-names></name> <name><surname>Yan</surname> <given-names>H</given-names></name> <name><surname>Zhao</surname> <given-names>YX</given-names></name> <name><surname>Liu</surname> <given-names>XY</given-names></name></person-group>. <article-title>Prognostic value of morning blood pressure surge in clinical events: a meta-analysis of longitudinal studies</article-title>. <source>J Stroke Cerebrovasc Dis</source>. (<year>2015</year>) <volume>24</volume>:<fpage>362</fpage>&#x2013;<lpage>9</lpage>. doi: <pub-id pub-id-type="doi">10.1016/j.jstrokecerebrovasdis.2014.09.001</pub-id>, PMID: <pub-id pub-id-type="pmid">25511618</pub-id></citation></ref>
<ref id="ref27"><label>27.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Lees</surname> <given-names>KR</given-names></name> <name><surname>Bluhmki</surname> <given-names>E</given-names></name> <name><surname>von Kummer</surname> <given-names>R</given-names></name> <name><surname>Brott</surname> <given-names>TG</given-names></name> <name><surname>Toni</surname> <given-names>D</given-names></name> <name><surname>Grotta</surname> <given-names>JC</given-names></name> <etal/></person-group>. <article-title>Time to treatment with intravenous alteplase and outcome in stroke: an updated pooled analysis of ECASS, ATLANTIS, NINDS, and EPITHET trials</article-title>. <source>Lancet</source>. (<year>2010</year>) <volume>375</volume>:<fpage>1695</fpage>&#x2013;<lpage>703</lpage>. doi: <pub-id pub-id-type="doi">10.1016/S0140-6736(10)60491-6</pub-id>, PMID: <pub-id pub-id-type="pmid">20472172</pub-id></citation></ref>
<ref id="ref28"><label>28.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Scheer</surname> <given-names>FA</given-names></name> <name><surname>Hilton</surname> <given-names>MF</given-names></name> <name><surname>Mantzoros</surname> <given-names>CS</given-names></name> <name><surname>Shea</surname> <given-names>SA</given-names></name></person-group>. <article-title>Adverse metabolic and cardiovascular consequences of circadian misalignment</article-title>. <source>Proc Natl Acad Sci USA</source>. (<year>2009</year>) <volume>106</volume>:<fpage>4453</fpage>&#x2013;<lpage>8</lpage>. doi: <pub-id pub-id-type="doi">10.1073/pnas.0808180106</pub-id>, PMID: <pub-id pub-id-type="pmid">19255424</pub-id></citation></ref>
<ref id="ref29"><label>29.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Gumz</surname> <given-names>ML</given-names></name> <name><surname>Shimbo</surname> <given-names>D</given-names></name> <name><surname>Abdalla</surname> <given-names>M</given-names></name> <name><surname>Balijepalli</surname> <given-names>RC</given-names></name> <name><surname>Benedict</surname> <given-names>C</given-names></name> <name><surname>Chen</surname> <given-names>Y</given-names></name> <etal/></person-group>. <article-title>Medicine: circadian rhythm of blood pressure and chronotherapy for hypertension - 2021 NHLBI workshop report</article-title>. <source>Hypertension</source>. (<year>2023</year>) <volume>80</volume>:<fpage>503</fpage>&#x2013;<lpage>22</lpage>. doi: <pub-id pub-id-type="doi">10.1161/HYPERTENSIONAHA.122.19372</pub-id>, PMID: <pub-id pub-id-type="pmid">36448463</pub-id></citation></ref>
<ref id="ref30"><label>30.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Parati</surname> <given-names>G</given-names></name> <name><surname>Stergiou</surname> <given-names>GS</given-names></name> <name><surname>Asmar</surname> <given-names>R</given-names></name> <name><surname>Bilo</surname> <given-names>G</given-names></name> <name><surname>de Leeuw</surname> <given-names>P</given-names></name> <name><surname>Imai</surname> <given-names>Y</given-names></name> <etal/></person-group>. <article-title>European Society of Hypertension guidelines for blood pressure monitoring at home: a summary report of the second international consensus conference on home blood pressure monitoring</article-title>. <source>J Hypertens</source>. (<year>2008</year>) <volume>26</volume>:<fpage>1505</fpage>&#x2013;<lpage>26</lpage>. doi: <pub-id pub-id-type="doi">10.1097/HJH.0b013e328308da66</pub-id>, PMID: <pub-id pub-id-type="pmid">18622223</pub-id></citation></ref>
<ref id="ref31"><label>31.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Ohkubo</surname> <given-names>T</given-names></name> <name><surname>Hozawa</surname> <given-names>A</given-names></name> <name><surname>Yamaguchi</surname> <given-names>J</given-names></name> <name><surname>Kikuya</surname> <given-names>M</given-names></name> <name><surname>Ohmori</surname> <given-names>K</given-names></name> <name><surname>Michimata</surname> <given-names>M</given-names></name> <etal/></person-group>. <article-title>Prognostic significance of the nocturnal decline in blood pressure in individuals with and without high 24-h blood pressure: the Ohasama study</article-title>. <source>J Hypertens</source>. (<year>2002</year>) <volume>20</volume>:<fpage>2183</fpage>&#x2013;<lpage>9</lpage>. doi: <pub-id pub-id-type="doi">10.1097/00004872-200211000-00017</pub-id>, PMID: <pub-id pub-id-type="pmid">12409956</pub-id></citation></ref>
<ref id="ref32"><label>32.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Billinger</surname> <given-names>SA</given-names></name> <name><surname>Arena</surname> <given-names>R</given-names></name> <name><surname>Bernhardt</surname> <given-names>J</given-names></name> <name><surname>Eng</surname> <given-names>JJ</given-names></name> <name><surname>Franklin</surname> <given-names>BA</given-names></name> <name><surname>Johnson</surname> <given-names>CM</given-names></name> <etal/></person-group>. <article-title>Physical activity and exercise recommendations for stroke survivors: a statement for healthcare professionals from the American Heart Association/American Stroke Association</article-title>. <source>Stroke</source>. (<year>2014</year>) <volume>45</volume>:<fpage>2532</fpage>&#x2013;<lpage>53</lpage>. doi: <pub-id pub-id-type="doi">10.1161/STR.0000000000000022</pub-id></citation></ref>
<ref id="ref33"><label>33.</label><citation citation-type="journal"><person-group person-group-type="author"><name><surname>Brandt</surname> <given-names>MM</given-names></name> <name><surname>Cheng</surname> <given-names>C</given-names></name> <name><surname>Merkus</surname> <given-names>D</given-names></name> <name><surname>Duncker</surname> <given-names>DJ</given-names></name> <name><surname>Sorop</surname> <given-names>O</given-names></name></person-group>. <article-title>Mechanobiology of microvascular function and structure in health and disease: focus on the coronary circulation</article-title>. <source>Front Physiol</source>. (<year>2021</year>) <volume>12</volume>:<fpage>771960</fpage>. doi: <pub-id pub-id-type="doi">10.3389/fphys.2021.771960</pub-id>, PMID: <pub-id pub-id-type="pmid">35002759</pub-id></citation></ref>
</ref-list>
</back>
</article>