{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T13:40:41Z","timestamp":1777902041142,"version":"3.51.4"},"reference-count":25,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Science Progress"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:p>\n                    <jats:bold>Objective:<\/jats:bold>\n                    Emerging evidence suggests a potential link between cholesterol metabolism and bleeding. We aimed to examine the causal effect of low-density lipoprotein cholesterol (LDL-C) or lipid-lowering drugs on bleeding outcomes.\n                    <jats:bold>Methods:<\/jats:bold>\n                    Two-sample Mendelian randomization (MR) analyses and two types of drug target MR were conducted to evaluate the associations of LDL-C levels with risks for three bleeding outcomes including intracerebral hemorrhage (ICH), gastrointestinal bleeding (GIBleeding), and hemorrhage from respiratory passages (HRP). Furthermore, the association between LDL-C and bleeding outcomes was re-evaluated in a retrospective cohort study involving patients with coronary artery disease (CAD).\n                    <jats:bold>Results:<\/jats:bold>\n                    MR analyses suggest that LDL-C levels are not associated with bleeding outcomes, including ICH, GIbleeding, and HRP. SMR also found no causal relationship between the use of lipid-lowering drugs (HMGCR inhibitors, PCSK9 inhibitors, and NPC1L1 inhibitor) and bleeding outcomes (ICH, GIbleeding, and HRP). Alleles at or near the HMGCR gene (mimicking the effect of statins) reducing LDL-C level expression levels are intended to elevate the risk of ICH (odds ratio (OR) 1.0018, 95% confidence interval (CI) 1.0001\u20131.0035, P\u2009=\u20090.043), independent of their lipid-lowering effect. In the CAD cohort with a 2-year follow up, LDL-C levels measured within the last 3 months of follow up were significantly associated with an increased risk of BARC criteria 3 to 5 grade bleeding (P\u2009&lt;\u20090.001) and showed a trend toward an increased risk of ICH (P\u2009=\u20090.051).\n                    <jats:bold>Conclusions:<\/jats:bold>\n                    These findings suggest a potential causal relationship between LDL-C levels and bleeding outcomes, particularly in patients using HMGCR inhibitors.\n                  <\/jats:p>","DOI":"10.1177\/00368504251375876","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T11:17:28Z","timestamp":1761045448000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Lipid, lipid-lowering drugs, and bleedings: A Mendelian randomization and retrospective study"],"prefix":"10.1177","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2890-9403","authenticated-orcid":false,"given":"Shaohua","family":"Guo","sequence":"first","affiliation":[{"name":"Beijing Friendship Hospital, Capital Medical University"},{"name":"Laboratory for Clinical Medicine, Capital Medical University, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6852-8538","authenticated-orcid":false,"given":"Sutao","family":"Hu","sequence":"additional","affiliation":[{"name":"Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6634-7635","authenticated-orcid":false,"given":"Hui","family":"Chen","sequence":"additional","affiliation":[{"name":"Beijing Friendship Hospital, Capital Medical University"},{"name":"Laboratory for Clinical Medicine, Capital Medical University, Beijing, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7056-6438","authenticated-orcid":false,"given":"Kang-Yin","family":"Chen","sequence":"additional","affiliation":[{"name":"Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,10,21]]},"reference":[{"key":"e_1_3_3_2_2","volume-title":"StatPearls [Internet]","author":"Craig M","unstructured":"Craig M, Yarrarapu SNS, Dimri M. Biochemistry, cholesterol. [Updated 2023 Aug 8]. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing, 2025 Jan-. Available from: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK513326\/#"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12872-022-02942-w"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2021.0929"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26125612"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000007853"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab418"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2004.00658.x"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2022.03.021"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/ehjcvp\/pvae092"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-022-02837-1"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyr036"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-9473(01)00097-4"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0579-z"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-147-8-200710160-00010"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.009449"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3538"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2018.06.011"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1136\/svn-2022-001612"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2024.0086"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.119.026402"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.043826"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-20-1051"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(98)00144-0"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000036092.23649.2E"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.3109\/10641968009037158"}],"container-title":["Science Progress"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/00368504251375876","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/00368504251375876","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/00368504251375876","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T11:17:45Z","timestamp":1777634265000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/00368504251375876"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10]]},"references-count":25,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,10]]}},"alternative-id":["10.1177\/00368504251375876"],"URL":"https:\/\/doi.org\/10.1177\/00368504251375876","relation":{},"ISSN":["0036-8504","2047-7163"],"issn-type":[{"value":"0036-8504","type":"print"},{"value":"2047-7163","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10]]},"article-number":"00368504251375876"}}