{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:12:34Z","timestamp":1788307954336,"version":"build-2803163510"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"24","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2018,12,18]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      In randomized trials (SHARP [Study of Heart and Renal Protection],\n                      <jats:styled-content style=\"fixed-case\">IMPROVE<\/jats:styled-content>\n                      \u2010IT [Improved Reduction of Outcomes: Vytorin Efficacy International Trial]), combination of statin and ezetimibe resulted in additional reduction of cardiovascular events. The reduction was greater in patients with type 2 diabetes mellitus (T2\n                      <jats:styled-content style=\"fixed-case\">DM<\/jats:styled-content>\n                      ), where elevated remnant cholesterol and high cardiovascular disease risk is characteristic. To evaluate possible causes behind these results, 40 patients eligible for cholecystectomy, randomized to simvastatin, ezetimibe, combined treatment (simvastatin+ezetimibe), or placebo treatment during 4\u00a0weeks before surgery, were studied.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Fasting blood samples were taken before treatment start and at the end (just before surgery). Bile samples and liver biopsies were collected during surgery. Hepatic gene expression levels were assessed with\n                      <jats:styled-content style=\"fixed-case\">qPCR<\/jats:styled-content>\n                      . Lipoprotein, apolipoprotein levels, and content of cholesterol, cholesteryl ester, and triglycerides were measured after lipoprotein fractionation. Lipoprotein subclasses were analyzed by nuclear magnetic resonance. Apolipoprotein affinity for human arterial proteoglycans (\n                      <jats:styled-content style=\"fixed-case\">PG<\/jats:styled-content>\n                      ) was measured. Biomarkers of cholesterol biosynthesis and intestinal absorption and bile lipid composition were analyzed using mass spectrometry. Combined treatment caused a statistically significant decrease in plasma remnant particles and apolipoprotein B (ApoB)\/lipoprotein content of cholesterol, cholesteryl esters, and triglycerides. All treatments reduced ApoB\u2010lipoprotein\n                      <jats:styled-content style=\"fixed-case\">PG<\/jats:styled-content>\n                      binding. Simvastatin and combined treatment modified the composition of lipoproteins. Changes in biomarkers of cholesterol synthesis and absorption and bile acid synthesis were as expected. No adverse events were found.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Combined treatment caused atheroprotective changes on ApoB\u2010lipoproteins, remnant particles, bile components, and in ApoB\u2010lipoprotein affinity for arterial\n                      <jats:styled-content style=\"fixed-case\">PG<\/jats:styled-content>\n                      . These effects might explain the decrease of cardiovascular events seen in the\n                      <jats:styled-content style=\"fixed-case\">SHARP<\/jats:styled-content>\n                      and\n                      <jats:styled-content style=\"fixed-case\">IMPROVE<\/jats:styled-content>\n                      \u2010\n                      <jats:styled-content style=\"fixed-case\">IT<\/jats:styled-content>\n                      trials.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Clinical Trial Registration<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      <jats:styled-content style=\"fixed-case\">URL<\/jats:styled-content>\n                      :\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.clinicaltrialsregister.eu\">www.clinicaltrialsregister.eu<\/jats:ext-link>\n                      . Unique identifier: 2006\u2010004839\u201030).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.118.009876","type":"journal-article","created":{"date-parts":[[2018,12,7]],"date-time":"2018-12-07T05:02:57Z","timestamp":1544158977000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":42,"title":["Ezetimibe in Combination With Simvastatin Reduces Remnant Cholesterol Without Affecting Biliary Lipid Concentrations in Gallstone Patients"],"prefix":"10.1161","volume":"7","author":[{"given":"Osman","family":"Ahmed","sequence":"first","affiliation":[{"name":"Division of Clinical Chemistry Department of Laboratory Medicine Karolinska Institutet Stockholm Sweden"},{"name":"Department of Biochemistry Faculty of Medicine Khartoum University Khartoum Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"Littmann","sequence":"additional","affiliation":[{"name":"Division of 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