{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T06:52:13Z","timestamp":1791528733173,"version":"4.3.4"},"reference-count":57,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100005351","name":"Neurosurgery Research and Education Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005351","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011906","name":"Joe Niekro Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011906","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013490","name":"Brain Aneurysm Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013490","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019585","name":"Bee Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019585","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013568","name":"Aneurysm and AVM Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013568","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["Grant numbers: R01NS111119\u201001A1 UL1TR002736 KL2TR002737"],"award-info":[{"award-number":["Grant numbers: R01NS111119\u201001A1 UL1TR002736 KL2TR002737"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cerebral cavernous malformations (CCM) are vascular lesions prone to hemorrhage, but the influence of modifiable cardiovascular risk factors and commonly prescribed therapies on bleeding risk remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a systematic review and meta\u2010analysis according to PRISMA 2020. PubMed\/MEDLINE, Embase, and Scopus were searched from inception through August 31, 2025. Eligible observational studies and randomized trials reported adults with CCM stratified by modifiable cardiovascular risk factors or systemic therapies. Hemorrhagic presentation at diagnosis and prospective symptomatic hemorrhage or rebleeding during follow\u2010up were extracted and interpreted as distinct clinical endpoints. Comparable adjusted and crude estimates were pooled separately using random\u2010effects models; randomized trials with non\u2010comparable populations or endpoints were summarized narratively. Risk of bias and certainty of evidence were assessed using design\u2010appropriate Cochrane tools and GRADE, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 1275 records identified, 30 full texts were reviewed, and 22 studies met inclusion criteria, comprising 7331 patients with CCM. Most pooled analyses evaluated hemorrhagic presentation at diagnosis. Smoking was associated with increased odds of hemorrhagic presentation (aOR 1.41, 95% CI 1.03\u20131.93), and obesity showed an uncertain signal toward higher odds (aOR 1.77, 95% CI 1.00\u20133.13). Antithrombotic therapy was associated with lower odds of hemorrhagic presentation (aOR 0.46, 95% CI 0.29\u20130.73), while statins showed a nonsignificant association (aOR 0.79, 95% CI 0.52\u20131.20). Randomized propranolol and atorvastatin trials were considered separately because their prospective endpoints and trial populations were not directly comparable with the observational presentation\u2010based analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Evidence regarding systemic cardiovascular factors and therapies in CCM remains sparse and predominantly of low or very low certainty. The observed associations are preliminary, may reflect residual confounding and treatment\u2010selection bias, and should not be interpreted as causal or as direct estimates of future hemorrhage risk. Prospective multicenter studies with standardized clinical and imaging definitions are needed before these findings can inform treatment decisions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.71829","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T06:44:36Z","timestamp":1791528276000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impact of Modifiable Cardiovascular Risk Factors and Protective Therapies on Hemorrhagic Events in Cerebral Cavernous Malformations: A Systematic Review and Meta\u2010Analysis"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3637-5033","authenticated-orcid":false,"given":"Sai","family":"Sanikommu","sequence":"first","affiliation":[{"name":"Department of Neurological Surgery University of Miami School of Medicine  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro N.","family":"Santos","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery University of Miami School of Medicine  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bashar","family":"Dawoud","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery University of Miami School of Medicine  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josiah J. Z.","family":"Sherman","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery University of Miami School of Medicine  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Wipplinger","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery Cleveland Clinic Weston  Weston Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emade","family":"Jaman","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery University of Miami School of Medicine  Miami Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jayro","family":"Toledo","sequence":"additional","affiliation":[{"name":"Department of Neurological Surgery University of Miami School of Medicine  Miami Florida 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