{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T05:32:38Z","timestamp":1763443958629,"version":"3.41.2"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ Cardiovasc Genet"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>Left ventricular ejection fraction (LVEF) and infarct size (ISZ) are key predictors of long-term survival after myocardial infarction (MI). However, little is known about the biochemical pathways driving LV dysfunction after MI. To identify novel biomarkers predicting post-MI LVEF and ISZ, we performed metabolic profiling in the GIPS-III randomized clinical trial (Glycometabolic Intervention as Adjunct to Primary Percutaneous Intervention in ST Elevation Myocardial Infarction). We also investigated the metabolic footprint of metformin, a drug associated with improved post-MI LV function in experimental studies.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              Participants were patients with ST-segment\u2013elevated MI who were randomly assigned to receive metformin or placebo for 4 months. Blood samples were obtained on admission, 24 hours post-MI, and 4 months post-MI. A total of 233 metabolite measures were quantified using nuclear magnetic resonance spectrometry. LVEF and ISZ were assessed 4 months post-MI. Twenty-four hours post-MI measurements of high-density lipoprotein (HDL) triglycerides (HDL-TG) predicted LVEF (\u03b2=1.90 [95% confidence interval (CI), 0.82 to 2.98];\n              <jats:italic>P<\/jats:italic>\n              =6.4\u00d710\n              <jats:sup>\u22124<\/jats:sup>\n              ) and ISZ (\u03b2=\u22120.41 [95% CI, \u22120.60 to \u22120.21];\n              <jats:italic>P<\/jats:italic>\n              =3.2\u00d710\n              <jats:sup>\u22125<\/jats:sup>\n              ). In addition, 24 hours post-MI measurements of medium HDL-TG (\u03b2=\u22120.40 [95% CI, \u22120.60 to \u22120.20];\n              <jats:italic>P<\/jats:italic>\n              =6.4\u00d72\u00d710\n              <jats:sup>\u22125<\/jats:sup>\n              ), small HDL-TG (\u03b2=\u22120.34 [95% CI, \u22120.53 to \u22120.14];\n              <jats:italic>P<\/jats:italic>\n              =7.3\u00d710\n              <jats:sup>\u22124<\/jats:sup>\n              ), and the triglyceride content of very large HDL (\u03b2=\u22120.38 [95% CI, \u22120.58 to \u22120.18];\n              <jats:italic>P<\/jats:italic>\n              =2.7\u00d710\n              <jats:sup>\u22124<\/jats:sup>\n              ) were associated with ISZ. After the 4-month treatment, the phospholipid content of very large HDL was lower in metformin than in placebo-treated patients (28.89% versus 38.79%;\n              <jats:italic>P<\/jats:italic>\n              =7.5\u00d710\n              <jats:sup>\u22125<\/jats:sup>\n              ); alanine levels were higher in the metformin group (0.46 versus 0.44 mmol\/L;\n              <jats:italic>P<\/jats:italic>\n              =2.4\u00d710\n              <jats:sup>\u22124<\/jats:sup>\n              ).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>HDL triglyceride concentrations predict post-MI LVEF and ISZ. Metformin increases alanine levels and reduces the phospholipid content in very large HDL particles.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Clinical Trial Registration\u2014<\/jats:title>\n            <jats:p>\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01217307\">https:\/\/clinicaltrials.gov\/ct2\/show\/NCT01217307<\/jats:ext-link>\n              . Unique Identifier: NCT01217307.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circgenetics.116.001564","type":"journal-article","created":{"date-parts":[[2017,1,19]],"date-time":"2017-01-19T02:55:58Z","timestamp":1484794558000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":17,"title":["Effect of Metformin on Metabolites and Relation With Myocardial Infarct Size and Left Ventricular Ejection Fraction After Myocardial Infarction"],"prefix":"10.1161","volume":"10","author":[{"given":"Ruben N.","family":"Eppinga","sequence":"first","affiliation":[{"name":"From the Department of Cardiology (R.N.E., E.L., D.J.v.V., P.v.d.H.), Department of Endocrinology (R.P.F.D.), Department of Critical Care (I.C.C.v.d.H.), University of Groningen, University Medical Center Groningen, The Netherlands; Division of Heart and Lungs, Department of Cardiology (D.K., F.W.A.), Julius Center for Health Sciences and Primary Care (G.W.D.), University Medical Center Utrecht, The Netherlands; Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht (F.W..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Kofink","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology (R.N.E., E.L., D.J.v.V., P.v.d.H.), Department of Endocrinology (R.P.F.D.), Department of Critical Care (I.C.C.v.d.H.), University of Groningen, University Medical Center Groningen, The Netherlands; Division of Heart and Lungs, Department of Cardiology (D.K., F.W.A.), Julius Center for Health Sciences and Primary Care (G.W.D.), University Medical Center Utrecht, The Netherlands; Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht (F.W..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin P.F.","family":"Dullaart","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology (R.N.E., E.L., D.J.v.V., P.v.d.H.), Department of Endocrinology (R.P.F.D.), Department of Critical Care (I.C.C.v.d.H.), University of Groningen, University Medical Center Groningen, The Netherlands; Division of Heart and Lungs, Department of Cardiology (D.K., F.W.A.), Julius Center for Health Sciences and Primary Care (G.W.D.), University Medical Center Utrecht, The Netherlands; Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht (F.W..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geertje W.","family":"Dalmeijer","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology (R.N.E., E.L., D.J.v.V., P.v.d.H.), Department of Endocrinology (R.P.F.D.), Department of Critical Care (I.C.C.v.d.H.), University of Groningen, University Medical Center Groningen, The Netherlands; Division of Heart and Lungs, Department of Cardiology (D.K., F.W.A.), Julius Center for Health Sciences and Primary Care (G.W.D.), University Medical Center Utrecht, The Netherlands; Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht (F.W..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erik","family":"Lipsic","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology (R.N.E., E.L., D.J.v.V., P.v.d.H.), Department of Endocrinology (R.P.F.D.), Department of Critical Care (I.C.C.v.d.H.), University of Groningen, University Medical Center Groningen, The Netherlands; Division of Heart and Lungs, Department of Cardiology (D.K., F.W.A.), Julius Center for Health Sciences and Primary Care (G.W.D.), University Medical Center Utrecht, The Netherlands; Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht (F.W..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dirk J.","family":"van Veldhuisen","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology (R.N.E., E.L., D.J.v.V., P.v.d.H.), Department of Endocrinology (R.P.F.D.), Department of Critical Care (I.C.C.v.d.H.), University of Groningen, University Medical Center Groningen, The Netherlands; Division of Heart and Lungs, Department of Cardiology (D.K., F.W.A.), Julius Center for Health Sciences and Primary Care (G.W.D.), University Medical Center Utrecht, The Netherlands; Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht (F.W..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iwan C.C.","family":"van der Horst","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology (R.N.E., E.L., D.J.v.V., P.v.d.H.), Department of Endocrinology (R.P.F.D.), Department of Critical Care (I.C.C.v.d.H.), University of Groningen, University Medical Center Groningen, The Netherlands; Division of Heart and Lungs, Department of Cardiology (D.K., F.W.A.), Julius Center for Health Sciences and Primary Care (G.W.D.), University Medical Center Utrecht, The Netherlands; Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht (F.W..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Folkert W.","family":"Asselbergs","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology (R.N.E., E.L., D.J.v.V., P.v.d.H.), Department of Endocrinology (R.P.F.D.), Department of Critical Care (I.C.C.v.d.H.), University of Groningen, University Medical Center Groningen, The Netherlands; Division of Heart and Lungs, Department of Cardiology (D.K., F.W.A.), Julius Center for Health Sciences and Primary Care (G.W.D.), University Medical Center Utrecht, The Netherlands; Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht (F.W..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pim","family":"van der Harst","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology (R.N.E., E.L., D.J.v.V., P.v.d.H.), Department of Endocrinology (R.P.F.D.), Department of Critical Care (I.C.C.v.d.H.), University of Groningen, University Medical Center Groningen, The Netherlands; Division of Heart and Lungs, Department of Cardiology (D.K., F.W.A.), Julius Center for Health Sciences and Primary Care (G.W.D.), University Medical Center Utrecht, The Netherlands; Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, Utrecht (F.W..."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61223-9"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.11.048"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.2007.122622"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10557-012-6413-1"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.3315"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2013.164"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-14-3400"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2009.240"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-1452"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/dme.13097"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0145719"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2014.01.019"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehs020"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1039\/c3mb70227h"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(93)90213-K"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.114.000216"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr597"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.echo.2014.10.003"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0168-8227(93)90127-Q"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.2001.281.2.E275"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-0658"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2261-14-143"},{"key":"e_1_3_3_24_2","first-page":"297","article-title":"Low admission triglyceride and mortality in acute coronary syndrome patients.","volume":"18","author":"Khawaja OA","year":"2011","unstructured":"Khawaja OA, Hatahet H, Cavalcante J, Khanal S, Al-Mallah MH. 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