{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T13:00:44Z","timestamp":1782824444205,"version":"3.54.5"},"reference-count":36,"publisher":"Korean Stroke Society","issue":"1","license":[{"start":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T00:00:00Z","timestamp":1767312000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2022YFC3602500"],"award-info":[{"award-number":["2022YFC3602500"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2022YFC3602505"],"award-info":[{"award-number":["2022YFC3602505"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Beijing High-level Public Health Technical Personnel Construction Project","award":["-03-12"],"award-info":[{"award-number":["-03-12"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82425101"],"award-info":[{"award-number":["82425101"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Noncommunicable Chronic Diseases-National Science and Technology Major Project","award":["2023ZD0504800"],"award-info":[{"award-number":["2023ZD0504800"]}]},{"name":"Noncommunicable Chronic Diseases-National Science and Technology Major Project","award":["2023ZD0504801"],"award-info":[{"award-number":["2023ZD0504801"]}]},{"name":"Noncommunicable Chronic Diseases-National Science and Technology Major Project","award":["2023ZD0504802"],"award-info":[{"award-number":["2023ZD0504802"]}]},{"name":"Noncommunicable Chronic Diseases-National Science and Technology Major Project","award":["2023ZD0504803"],"award-info":[{"award-number":["2023ZD0504803"]}]},{"name":"Noncommunicable Chronic Diseases-National Science and Technology Major Project","award":["2023ZD0504804"],"award-info":[{"award-number":["2023ZD0504804"]}]},{"DOI":"10.13039\/501100009592","name":"Beijing Municipal Science & Technology Commission","doi-asserted-by":"crossref","award":["Z231100004823036"],"award-info":[{"award-number":["Z231100004823036"]}],"id":[{"id":"10.13039\/501100009592","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100005024","name":"Beijing Postdoctoral Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["j-stroke.org"],"crossmark-restriction":true},"short-container-title":["J Stroke"],"published-print":{"date-parts":[[2026,1,31]]},"abstract":"<jats:p>Background and Purpose Bilirubin has potent antioxidant, anti-inflammatory, and neuroprotective effects. Herein, we investigated whether total bilirubin (TBIL) modifies the association between hypertension and cerebral small vessel disease (CSVD).Methods Data were obtained from the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events study. TBIL and direct bilirubin (DBIL) levels were assayed using fasting venous blood samples. Indirect bilirubin (IBIL) was calculated by subtracting DBIL from TBIL. TBIL was stratified as \u226417 \u03bcmol\/L and &gt;17 \u03bcmol\/L based on the biological relevance of Gilbert\u2019s syndrome. Hypertension was defined as blood pressure \u2265140\/90 mm Hg, self-reported hypertension history, or current use of antihypertensive agents. White matter hyperintensity, lacunes, cerebral microbleeds, and enlarged perivascular spaces were evaluated using magnetic resonance imaging and used to rate CSVD burden according to the criteria proposed by Wardlaw et al. and Rothwell et al.Results This study included 3,061 participants, with a mean age of 61.2\u00b16.7 years and 46.5% males. After adjusting for confounders, hypertension was associated with increased odds of presence of CSVD (Wardlaw: odds ratio [OR]=1.86, 95% confidence interval [CI] 1.41\u20132.44, P&lt;0.001; Rothwell: OR=1.84, 95% CI 1.43\u20132.38, P&lt;0.001) and higher modified total CSVD burden (common OR: 1.85, 95% CI 1.45\u20132.36, P&lt;0.001) in participants with TBIL \u226417 \u03bcmol\/L but not in TBIL &gt;17 \u03bcmol\/L (P for interaction &lt;0.05). Johnson\u2013Neyman analyses showed cut-off concentrations of 22.3\u201322.4 \u03bcmol\/L for effect modification by TBIL. IBIL contributed to effect modification, whereas DBIL did not.Conclusions Mildly elevated TBIL may modify the association between hypertension and CSVD.<\/jats:p>","DOI":"10.5853\/jos.2025.01935","type":"journal-article","created":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T01:57:01Z","timestamp":1767319021000},"page":"85-96","update-policy":"https:\/\/doi.org\/10.5853\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effect Modification by Total Bilirubin on the Association Between Hypertension and Cerebral Small Vessel Disease"],"prefix":"10.5853","volume":"28","author":[{"given":"Zhang","family":"Xia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueli","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingying","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengxing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiemin","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2725-2788","authenticated-orcid":true,"given":"Yilong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3082-6789","authenticated-orcid":true,"given":"Yuesong","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"3882","reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2018.3122"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1159\/000533678"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1111\/ijs.12466"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-023-01195-9"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1161\/hypertensionaha.119.12830"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1002\/ana.23554"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.12968\/hmed.2023.0092"},{"key":"ref8","first-page":"55","volume-title":"The 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