{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T05:18:07Z","timestamp":1787807887055,"version":"build-2784847793"},"reference-count":30,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>In secondary prevention after ischemic stroke or TIA, LDL-C\u202f&amp;lt;\u202f1.8\u202fmmol\/L is associated with a lower risk of recurrent vascular events. However, evidence remains limited in real-world patients with ischemic stroke, especially those with significant large-artery atherosclerotic stenosis. In particular, few studies have evaluated the impact of sustained LDL-C target attainment on recurrent ischemic cerebrovascular events by using LDL-C target attainment as a time-varying exposure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively studied 933 patients with ischemic stroke who had baseline LDL-C levels \u22651.8\u202fmmol\/L at admission. Significant large-artery disease (LAD) was defined as \u226550% intracranial or extracranial atherosclerotic stenosis. LDL-C target attainment was defined as &amp;lt;1.8\u202fmmol\/L. The primary outcome was recurrent ischemic cerebrovascular events. Time-dependent Cox models evaluated the association between time-varying LDL-C target attainment and recurrence, and effect modification by LAD status was assessed. The proportion of follow-up time with LDL-C\u202f\u2265\u202f1.8\u202fmmol\/L was additionally assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 933 patients, 369 had LAD and 564 did not. During follow-up, 102 recurrent ischemic cerebrovascular events occurred. In the fully adjusted model, time-varying LDL-C target attainment was associated with lower recurrence risk [hazard ratio (HR)\u202f=\u202f0.399, 95% confidence interval (CI): 0.269\u20130.593,\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001]. This association was stronger in patients with LAD (HR\u202f=\u202f0.282, 95% CI: 0.168\u20130.475, p\u202f&amp;lt;\u202f0.001) than in those without LAD (HR\u202f=\u202f0.530, 95% CI: 0.288\u20130.976;\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.042; P for interaction\u202f=\u202f0.041). Each 10% increase in the proportion of follow-up time with LDL-C\u202f\u2265\u202f1.8\u202fmmol\/L was associated with higher recurrence risk (HR\u202f=\u202f1.189, 95% CI 1.127\u20131.254), with a stronger association in LAD patients (P for interaction\u202f=\u202f0.008).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Among patients with ischemic stroke who had baseline LDL-C levels \u22651.8\u202fmmol\/L at admission, sustained LDL-C target attainment was associated with a lower risk of recurrence after ischemic stroke. This association was particularly evident in patients with significant LAD. Sustained LDL-C control may support risk stratification and secondary prevention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1902614","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T04:26:12Z","timestamp":1787804772000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Sustained LDL-C target attainment and recurrent ischemic cerebrovascular events after ischemic stroke: effect modification by large-artery disease"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiaofeng","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Clinical Medicine, Shandong Second Medical University","place":["Weifang, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Niu","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, Shandong Second Medical University","place":["Weifang, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yikang","family":"Li","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, Shandong Second Medical University","place":["Weifang, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Weifang People's Hospital","place":["Weifang, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruizhi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Weifang People's Hospital","place":["Weifang, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoping","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Neurology, Weifang People's Hospital","place":["Weifang, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2459","DOI":"10.1093\/eurheartj\/ehx144","article-title":"Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European atherosclerosis society consensus panel","volume":"38","author":"Ference","year":"2017","journal-title":"Eur Heart J"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"e1082","DOI":"10.1161\/CIR.0000000000000625","article-title":"AHA\/ACC\/AACVPR\/AAPA\/ABC\/ACPM\/ADA\/AGS\/APhA\/ASPC\/NLA\/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology\/American Heart Association task force on clinical practice guidelines","volume":"139","author":"Grundy","year":"2018","journal-title":"Circulation"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1056\/NEJMoa061894","article-title":"High-dose atorvastatin after stroke or transient ischemic attack","volume":"355","author":"Amarenco","year":"2006","journal-title":"N Engl J Med"},{"key":"ref4","first-page":"1670","article-title":"Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials","volume-title":"Lancet","author":"Baigent","year":"2010"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1056\/NEJMoa1910355","article-title":"A comparison of two LDL cholesterol targets after ischemic stroke","volume":"382","author":"Amarenco","year":"2020","journal-title":"N Engl J Med"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/s12944-020-01427-z","article-title":"LDL-cholesterol change and goal attainment following statin intensity titration among Asians in primary care: a retrospective cohort study","volume":"20","author":"Fang","year":"2021","journal-title":"Lipids Health Dis"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"e364","DOI":"10.1161\/STR.0000000000000375","article-title":"2021 guideline for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline from the American Heart Association\/American Stroke Association","volume":"52","author":"Kleindorfer","year":"2021","journal-title":"Stroke"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"4359","DOI":"10.1093\/eurheartj\/ehaf190","article-title":"Focused update of the 2019 ESC\/EAS guidelines for the management of dyslipidaemias","volume":"46","author":"Mach","year":"2025","journal-title":"Eur Heart J"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1305","DOI":"10.1056\/NEJMoa043033","article-title":"Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis","volume":"352","author":"Chimowitz","year":"2005","journal-title":"N Engl J Med"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1056\/NEJM199108153250701","article-title":"Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis","volume":"325","author":"Barnett","year":"1991","journal-title":"N Engl J Med"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"e021855","DOI":"10.1161\/JAHA.121.021855","article-title":"Low-density lipoprotein cholesterol and risk of recurrent vascular events in Chinese patients with ischemic stroke with and without significant atherosclerosis","volume":"10","author":"Lau","year":"2021","journal-title":"J Am Heart Assoc"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1400","DOI":"10.1001\/archneurol.2009.210","article-title":"Lipid profile components and risk of ischemic stroke: the northern Manhattan study (NOMAS)","volume":"66","author":"Willey","year":"2009","journal-title":"Arch Neurol"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1161\/STROKEAHA.116.014436","article-title":"Lipoprotein(a) levels and recurrent vascular events after first ischemic stroke","volume":"48","author":"Lange","year":"2017","journal-title":"Stroke"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.12968\/hmed.2024.0711","article-title":"The correlation between lipoprotein(a) and cognitive impairment in patients with ischemic stroke","volume":"86","author":"Zhang","year":"2025","journal-title":"Br J Hosp Med"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"2313","DOI":"10.1093\/eurheartj\/ehz962","article-title":"Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European atherosclerosis society consensus panel","volume":"41","author":"Bor\u00e9n","year":"2020","journal-title":"Eur Heart J"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1630","DOI":"10.1016\/j.cell.2022.04.004","article-title":"Atherosclerosis: recent developments","volume":"185","author":"Bj\u00f6rkegren","year":"2022","journal-title":"Cell"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"1474","DOI":"10.1161\/ATVBAHA.124.319396","article-title":"Differences in stable and unstable atherosclerotic plaque","volume":"44","author":"Kawai","year":"2024","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1161\/STROKEAHA.119.028405","article-title":"Higher plaque burden of middle cerebral artery is associated with recurrent ischemic stroke: a quantitative magnetic resonance imaging study","volume":"51","author":"Ran","year":"2020","journal-title":"Stroke"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"3022","DOI":"10.1007\/s00330-023-10278-y","article-title":"Association of plaque characteristics with long-term stroke recurrence in patients with intracranial atherosclerotic disease: a 3D high-resolution MRI-based cohort study","volume":"34","author":"Lv","year":"2024","journal-title":"Eur Radiol"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1161\/CIRCRESAHA.115.306301","article-title":"Endothelial cell dysfunction and the pathobiology of atherosclerosis","volume":"118","author":"Gimbrone","year":"2016","journal-title":"Circ Res"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1093\/cvr\/cvx226","article-title":"Endothelial permeability, LDL deposition, and cardiovascular risk factors-a review","volume":"114","author":"Mundi","year":"2018","journal-title":"Cardiovasc Res"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1161\/CIRCRESAHA.116.308537","article-title":"Pleiotropic effects of statins on the cardiovascular system","volume":"120","author":"Oesterle","year":"2017","journal-title":"Circ Res"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1771","DOI":"10.1001\/jama.2022.5218","article-title":"Effect of Alirocumab added to high-intensity statin therapy on coronary atherosclerosis in patients with acute myocardial infarction: the PACMAN-AMI randomized clinical trial","volume":"327","author":"R\u00e4ber","year":"2022","journal-title":"JAMA"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1093\/ehjcvp\/pvz022","article-title":"PCSK9 and inflammation: a review of experimental and clinical evidence","volume":"5","author":"Momtazi-Borojeni","year":"2019","journal-title":"Eur Heart J Cardiovasc Pharmacother"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"264","DOI":"10.4103\/hm.HM-D-24-00106","article-title":"Effects of a diet rich in polyphenols on lipid metabolism: an updated narrative review","volume":"9","author":"Scavuzzi","year":"2025","journal-title":"Heart Mind"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1007\/s10522-025-10279-y","article-title":"Mechanisms of endothelial senescence and vascular aging","volume":"26","author":"Li","year":"2025","journal-title":"Biogerontology"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"e033341","DOI":"10.1161\/JAHA.123.033341","article-title":"Vascular aging in ischemic stroke","volume":"13","author":"Liu","year":"2024","journal-title":"J Am Heart Assoc"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1032","DOI":"10.1016\/j.jstrokecerebrovasdis.2014.12.033","article-title":"Neurologic symptom severity after a recent noncardioembolic stroke and recurrent vascular risk","volume":"24","author":"Park","year":"2015","journal-title":"J Stroke Cerebrovasc Dis"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"174","DOI":"10.4103\/hm.HM-D-24-00163","article-title":"National Institute of health stroke scale score mediated the relationship between systemic inflammatory response index, high-sensitivity C-reactive protein, and functional prognosis of acute ischemic stroke: a prospective cross-sectional study","volume":"9","author":"Liu","year":"2025","journal-title":"Heart Mind"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"328","DOI":"10.4103\/hm.HM-D-24-00068","article-title":"From heart to mind: research advances in the link between coronary artery disease and mental stress-a narrative review","volume":"9","author":"Li","year":"2025","journal-title":"Heart Mind"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1902614\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T04:26:14Z","timestamp":1787804774000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2026.1902614\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,27]]},"references-count":30,"alternative-id":["10.3389\/fneur.2026.1902614"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2026.1902614","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,27]]},"article-number":"1902614"}}