{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T10:51:06Z","timestamp":1791456666844,"version":"4.3.4"},"reference-count":46,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2025M782188"],"award-info":[{"award-number":["2025M782188"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62522119"],"award-info":[{"award-number":["62522119"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Evidence Based Medicine"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>This study aimed to investigate the association between elevated blood pressure (BP) and subcortical gray matter structures, and to elucidate the causality and underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study enrolled 1012 participants from a multicenter, population\u2010based cohort study in China. Generalized linear models were used to evaluate the associations between different degrees of BP and subcortical gray matter volumes. Mendelian randomization analysis based on genome\u2010wide data was performed to investigate causal relationships. We further conducted mediation analysis to analyze whether these associations were mediated by dysfunctional brain clearance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compared with the lowest group of systolic BP (SBP) &lt; 120\u00a0mmHg and diastolic BP (DBP) &lt; 80\u00a0mmHg, elevated BP was associated with larger subcortical gray matter volumes, including caudate volumes (SBP\/DBP 130\/80\u2013140\/90 mmHg:\n                      <jats:italic>\u03b2<\/jats:italic>\n                      = 0.19), putamen volumes (SBP\/DBP 130\/80\u2013140\/90 mmHg:\n                      <jats:italic>\u03b2<\/jats:italic>\n                      = 0.27; SBP\/DBP \u2265 140\/90 mmHg:\n                      <jats:italic>\u03b2<\/jats:italic>\n                      = 0.31), and pallidum volumes (SBP\/DBP 120\/80\u2013130\/80 mmHg:\n                      <jats:italic>\u03b2<\/jats:italic>\n                      = 0.25; SBP\/DBP 130\/80\u2013140\/90 mmHg:\n                      <jats:italic>\u03b2<\/jats:italic>\n                      = 0.28; SBP\/DBP \u2265 140\/90 mmHg:\n                      <jats:italic>\u03b2<\/jats:italic>\n                      = 0.25). Genetically determined hypertension was causally associated with increased volumes of subcortical gray matter (left caudate:\n                      <jats:italic>\u03b2<\/jats:italic>\n                      = 1.59; right caudate:\n                      <jats:italic>\u03b2<\/jats:italic>\n                      = 1.42; left putamen:\n                      <jats:italic>\u03b2<\/jats:italic>\n                      = 0.84; right putamen:\n                      <jats:italic>\u03b2<\/jats:italic>\n                      = 0.69; left pallidum:\n                      <jats:italic>\u03b2<\/jats:italic>\n                      = 0.59). The number of basal ganglia enlarged perivascular spaces (BG\u2010EPVS) mediated the relationship between elevated BP and larger volumes of subcortical gray matter.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Elevated BP is associated with larger subcortical gray matter volumes, mediated by an increased burden of BG\u2010EPVS. Our study provides novel evidence for the complex mechanisms linking higher BP levels to brain health.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jebm.70200","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T10:02:15Z","timestamp":1791453735000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Elevated Blood Pressure Is Causally Associated With Larger Subcortical Gray Matter Structure Through Perivascular Clearance Routes"],"prefix":"10.1111","author":[{"given":"Jing","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Radiology Beijing Friendship Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Radiology School of Clinical Medicine Beijing Tsinghua Changgung Hospital Tsinghua University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoshuai","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Radiology Beijing Friendship Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology and Evidence\u2010Based Medicine Unit Beijing Clinical Research Institute Beijing Friendship Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Radiology Beijing Friendship Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenghan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Radiology Beijing Friendship Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuohua","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiology Kailuan General Hospital  Hebei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shouling","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Cardiology Kailuan General Hospital  Hebei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Hui","sequence":"additional","affiliation":[{"name":"Department of Radiology Kailuan General Hospital  Hebei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenchang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Radiology Beijing Friendship Hospital Capital Medical University  Beijing China"},{"name":"Precision and Intelligence Medical Imaging Lab Beijing Friendship Hospital Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Radiology Beijing Friendship Hospital Capital Medical University  Beijing China"},{"name":"Precision and Intelligence Medical Imaging Lab Beijing Friendship Hospital Capital Medical University  Beijing China"},{"name":"Department of Health Data Science School of Medical Technology Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"issue":"11","key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/s41569-021-00559-8","article-title":"Global Epidemiology, Health Burden and Effective Interventions for Elevated Blood Pressure and Hypertension","volume":"18","author":"Zhou B.","year":"2021","journal-title":"Nature Reviews Cardiology"},{"issue":"6","key":"e_1_2_9_3_1","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1161\/CIRCULATIONAHA.115.018912","article-title":"Global Disparities of Hypertension Prevalence and Control: A Systematic Analysis of Population\u2010Based Studies From 90 Countries","volume":"134","author":"Mills K. 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