{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T03:54:24Z","timestamp":1791345264831,"version":"4.3.1"},"reference-count":72,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Statin effects extend beyond low-density lipoprotein cholesterol reduction, potentially modulating the metabolism of bioactive lipids (BALs), crucial for biological signaling and inflammation. These bioactive metabolites may serve as metabolic footprints, helping uncover underlying processes linked to pleiotropic effects of statins and yielding a better understanding of their cardioprotective properties. This study aimed to investigate the impact of high-intensity statin therapy versus placebo on plasma BALs in the JUPITER trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin; NCT00239681), a randomized primary prevention trial involving individuals with low-density lipoprotein cholesterol &lt;130 mg\/dL and high-sensitivity C-reactive protein \u22652 mg\/L.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      Using a nontargeted mass spectrometry approach, over 11\u2005000 lipid features were assayed from baseline and 1-year plasma samples from cardiovascular disease noncases from 2 nonoverlapping nested substudies: JUPITER\n                      <jats:sub>discovery<\/jats:sub>\n                      (n=589) and JUPITER\n                      <jats:sub>validation<\/jats:sub>\n                      (n=409). The effect of randomized allocation of rosuvastatin 20 mg versus placebo on BALs was examined by fitting a linear regression with delta values (\u2206=year 1\u2212baseline) adjusted for age and baseline levels of each feature. Significant associations in discovery were analyzed in the validation cohort. Multiple comparisons were adjusted using 2-stage overall false discovery rate.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>We identified 610 lipid features associated with statin randomization with significant replication (overall false discovery rate, &lt;0.05), including 26 with annotations. Statin therapy significantly increased levels of 276 features, including BALs with anti-inflammatory activity and arterial vasodilation properties. Concurrently, 334 features were significantly lowered by statin therapy, including arachidonic acid and proinflammatory and proplatelet aggregation BALs. By contrast, statin therapy reduced an eicosapentaenoic acid\u2013derived hydroxyeicosapentaenoic acid metabolite, which may be related to impaired glucose metabolism. Additionally, we observed sex-related differences in 6 lipid metabolites and 6 unknown features.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Statin allocation was significantly associated with upregulation of BALs with anti-inflammatory, antiplatelet aggregation and antioxidant properties and downregulation of BALs with proinflammatory and proplatelet aggregation activity, supporting the pleiotropic effects of statins beyond low-density lipoprotein cholesterol reduction.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.124.321058","type":"journal-article","created":{"date-parts":[[2024,6,6]],"date-time":"2024-06-06T05:01:01Z","timestamp":1717650061000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["One-Year Effects of High-Intensity Statin on Bioactive Lipids: Findings From the JUPITER Trial"],"prefix":"10.1161","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4034-0451","authenticated-orcid":true,"given":"Rosangela Akemi","family":"Hoshi","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Medicine (R.A.H., P.M.R., H.L.-G., S.M.), Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA."},{"name":"Division of Preventive Medicine (R.A.H., Y.L., P.M.R., R.J.G., H.L.-G., M.V.M., O.V.D., S.M.), Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA."},{"name":"Center for Lipid Metabolomics (R.A.H., Y.L., H.L.-G., O.V.D., S.M.), Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8492-9930","authenticated-orcid":true,"given":"Mona","family":"Alotaibi","sequence":"additional","affiliation":[{"name":"Department of Medicine (M.A., J.D.W., M.J.), University of California San Diego, La Jolla."},{"name":"Division of Pulmonary, Critical Care and Sleep Medicine (M.A.), University of California San Diego, La Jolla."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Preventive Medicine (R.A.H., Y.L., P.M.R., R.J.G., H.L.-G., M.V.M., O.V.D., S.M.), Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA."},{"name":"Center for Lipid Metabolomics (R.A.H., Y.L., H.L.-G., O.V.D., S.M.), Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeramie D.","family":"Watrous","sequence":"additional","affiliation":[{"name":"Department of Medicine (M.A., J.D.W., M.J.), University of California San Diego, La Jolla."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1249-4522","authenticated-orcid":true,"given":"Paul M","family":"Ridker","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine (R.A.H., P.M.R., H.L.-G., S.M.), Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA."},{"name":"Division of Preventive Medicine (R.A.H., Y.L., P.M.R., R.J.G., H.L.-G., M.V.M., O.V.D., S.M.), Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0697-8996","authenticated-orcid":true,"given":"Robert J.","family":"Glynn","sequence":"additional","affiliation":[{"name":"Division of Preventive Medicine (R.A.H., Y.L., P.M.R., R.J.G., H.L.-G., M.V.M., O.V.D., S.M.), Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4627-8545","authenticated-orcid":true,"given":"Charles N.","family":"Serhan","sequence":"additional","affiliation":[{"name":"Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine (C.N.S.), Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1265-9190","authenticated-orcid":true,"given":"Heike","family":"Luttmann-Gibson","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine (R.A.H., P.M.R., H.L.-G., S.M.), Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA."},{"name":"Division of Preventive Medicine (R.A.H., Y.L., P.M.R., R.J.G., H.L.-G., M.V.M., O.V.D., S.M.), Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA."},{"name":"Center for Lipid Metabolomics (R.A.H., Y.L., H.L.-G., O.V.D., S.M.), Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA."},{"name":"Department of Epidemiology, Harvard T.H. 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