{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:52:14Z","timestamp":1792803134781,"version":"4.5.0"},"reference-count":56,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Residual cardiovascular risk remains, despite achieving low-density lipoprotein cholesterol targets with high-intensity statins. Traditional risk scores are suboptimal. This study evaluated the prognostic utility of a 9-plex apolipoprotein panel in recent patients with acute coronary syndrome on statins and its role in predicting treatment benefit by alirocumab, a PCSK9 (proprotein convertase subtilisin\/kexin type 9) inhibitor, enabling precision medicine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>\n                      Baseline serum samples from 11\u2009843 participants in the ODYSSEY OUTCOMES trial (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      ; Unique identifier: NCT01663402) were analyzed using mass spectrometry to measure Apo(a), ApoA-I, ApoA-II, ApoA-IV, ApoB, ApoC-I, ApoC-II, ApoC-III, and ApoE. Using logistic regression, probabilities of major adverse cardiovascular events (MACE) and all-cause death over a median follow-up of 2.9 years were estimated based on baseline apolipoproteins and lipid concentrations. Clinical performance was assessed by comparing the area under the curve (AUC) of 3 models: the apolipoprotein panel, the lipid panel (total cholesterol, high-density lipoprotein cholesterol, and triglycerides), and a combination. In addition, prediction models estimating the treatment benefit of alirocumab by the apolipoprotein panel were developed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      The prognostic performance of the apolipoprotein panel for MACE showed an AUC (95% CI) of 0.648 (0.626\u20130.670), compared with 0.579 (0.557\u20130.602) for the lipid panel. For all-cause death, the apolipoprotein panel had an AUC of 0.699 (0.664\u20130.733), while the lipid panel had an AUC of 0.599 (0.564\u20130.635). Adding the apolipoprotein panel significantly improved the performance of the conventional lipid panel (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.0001): AUC, 0.659 (0.637\u20130.681) for MACE and 0.724 (0.691\u20130.756) for all-cause death. Higher risk for MACE based on the baseline apolipoprotein panel was found to predict greater treatment benefit with alirocumab.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>A multiplex apolipoprotein panel led to better prediction of MACE and all-cause death, beyond lipids, in patients with postacute coronary syndrome on optimized statin therapy. The panel also predicts the treatment benefit of alirocumab. Further validation of this approach is now needed, and if confirmed and improved, it could lead to better disease prediction and management in the future.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.124.322336","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T09:00:49Z","timestamp":1758790849000},"page":"2111-2123","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Multiplex Apolipoprotein Panel Improves Cardiovascular Event Prediction and Cardiovascular Outcome by Identifying Patients Who Benefit From Targeted PCSK9 Inhibitor Therapy"],"prefix":"10.1161","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3520-5869","authenticated-orcid":true,"given":"Esther","family":"Reijnders","sequence":"first","affiliation":[{"name":"Department of Clinical Chemistry and Laboratory Medicine (E.R., L.R.R., F. P.H.T.M.R., C.M.C.), Leiden University Medical Center, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4427-0128","authenticated-orcid":true,"given":"Patrick M.","family":"Bossuyt","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Data Science, Amsterdam UMC, The Netherlands (P.M.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3246-8359","authenticated-orcid":true,"given":"J. Wouter","family":"Jukema","sequence":"additional","affiliation":[{"name":"Department of Cardiology (J.W.J.), Leiden University Medical Center, the Netherlands."},{"name":"Department of Cardiology, Netherlands Heart Institute, Utrecht (J.W.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3737-3807","authenticated-orcid":true,"given":"L. Renee","family":"Ruhaak","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Laboratory Medicine (E.R., L.R.R., F. P.H.T.M.R., C.M.C.), Leiden University Medical Center, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4470-7959","authenticated-orcid":true,"given":"Fred P.H.T.M.","family":"Romijn","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Laboratory Medicine (E.R., L.R.R., F. P.H.T.M.R., C.M.C.), Leiden University Medical Center, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0046-0264","authenticated-orcid":true,"given":"Michael","family":"Szarek","sequence":"additional","affiliation":[{"name":"Division of Cardiology, University of Colorado School of Medicine, Aurora (M.S., G.G.S.)."},{"name":"CPC Clinical Research, Aurora, CO (M.S.)."},{"name":"State University of New York, Downstate Health Sciences University, Brooklyn (M.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5006-0528","authenticated-orcid":true,"given":"Stella","family":"Trompet","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (S.T.), Leiden University Medical Center, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1278-6245","authenticated-orcid":true,"given":"Deepak L.","family":"Bhatt","sequence":"additional","affiliation":[{"name":"Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, New York, NY (D.L.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9456-850X","authenticated-orcid":true,"given":"Vera A.","family":"Bittner","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Disease, University of Alabama at Birmingham (V.A.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Diaz","sequence":"additional","affiliation":[{"name":"Estudios Cardiol\u00f3gicos Latinoam\u00e9rica, Instituto Cardiovascular de Rosario, Argentina (R.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8145-8034","authenticated-orcid":true,"given":"Sergio","family":"Fazio","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Tarrytown, NY (S.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0516-1909","authenticated-orcid":true,"given":"Irena","family":"Stevanovic","sequence":"additional","affiliation":[{"name":"Sanofi, Paris, France (I.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8068-2440","authenticated-orcid":true,"given":"Shaun G.","family":"Goodman","sequence":"additional","affiliation":[{"name":"Canadian VIGOUR Centre, University of Alberta, Edmonton, Canada (S.G.G.)."},{"name":"St Michael\u2019s Hospital, University of Toronto, Ontario, Canada (S.G.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5450-8676","authenticated-orcid":true,"given":"Robert A.","family":"Harrington","sequence":"additional","affiliation":[{"name":"Weill Cornell Medicine, New York, NY (R.A.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7712-6750","authenticated-orcid":true,"given":"Harvey D.","family":"White","sequence":"additional","affiliation":[{"name":"Green Lane Cardiovascular Research Unit, Te Whatu Ora\u2013Health New Zealand, Te Toka Tumai, and University of Auckland (H.D.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6896-2941","authenticated-orcid":true,"given":"Philippe Gabriel","family":"Steg","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris-Cit\u00e9, INSERM-UMR1148, Assistance Publique-H\u00f4pitaux de Paris, H\u00f4pital Bichat, French Alliance for Cardiovascular Trials, and Institut Universitaire de France (P.G.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2954-0695","authenticated-orcid":true,"given":"Gregory G.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Division of Cardiology, University of Colorado School of Medicine, Aurora (M.S., G.G.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3565-1404","authenticated-orcid":true,"given":"Christa M.","family":"Cobbaert","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Laboratory Medicine (E.R., L.R.R., F. P.H.T.M.R., C.M.C.), Leiden University Medical Center, the Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2023.1264319"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2005.07.006"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2018.287037"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.2018-00184"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab551"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12014-024-09465-w"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehae258"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1177\/0004563219827620"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.121.057807"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2021.5083"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.123.030405"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11886-020-01323-z"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjpc\/zwac261"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2021.01.027"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2009.801"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.123.066398"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2019.10.057"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2402309"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2400201"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.11.042"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0000000000001160"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2010.01.003"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2021.12.032"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2016.11.065"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.122.321690"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2015.246702"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1515\/cclm-2018-0782"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2017.285098"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2013.09.018"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12014-023-09446-5"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ahj.2014.07.028"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1801174"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.10.039"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/18.6.499"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1093\/jalm\/jfae092"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2009.142810"},{"key":"e_1_3_3_38_2","doi-asserted-by":"crossref","unstructured":"Frank E. Harrell Jr Regression Modeling Strategies: With Applications to Linear Models Logistic Regression and Survival Analysis. Springer International Publishing; 2015.","DOI":"10.1007\/978-3-319-19425-7"},{"key":"e_1_3_3_39_2","unstructured":"Wickham H Miller E Smith D. haven: import and export \u201cSPSS \u201d \u201cstata\u201d and \u201cSAS\u201d files. 2025. Accessed March 2025. https:\/\/haven.tidyverse.org\/"},{"key":"e_1_3_3_40_2","unstructured":"Wickham H Fran\u00e7ois R Henry L M\u00fcller K Vaughan D. dplyr: a grammar of data manipulation. 2023. Accessed March 2025. https:\/\/dplyr.tidyverse.org\/"},{"key":"e_1_3_3_41_2","unstructured":"Wickham H Vaughan D Girlich M. tidyr: tidy messy data. 2024. Accessed March 2025. https:\/\/tidyr.tidyverse.org\/"},{"key":"e_1_3_3_42_2","unstructured":"HarrellJrFE. rms: regression modeling strategies. 2025. Accessed March 2025. https:\/\/cran.r-project.org\/web\/packages\/rms\/index.html"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-12-77"},{"key":"e_1_3_3_44_2","first-page":"7","article-title":"Diagnostic checking in regression relationships.","volume":"2","author":"Zeileis A","year":"2002","unstructured":"Zeileis A, Hothorn T. Diagnostic checking in regression relationships. R News. 2002;2:7\u201310.","journal-title":"R News"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2018.1470"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2019.1041"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R071233"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.037184"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31652-0"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2019.3780"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2019.08.014"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10071578"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2007.11.017"},{"key":"e_1_3_3_54_2","first-page":"822","article-title":"A splice-junction mutation responsible for familial apolipoprotein A-II deficiency.","volume":"46","author":"Deeb SS","year":"1990","unstructured":"Deeb SS, Takata K, Peng RL, Kajiyama G, Albers JJ. A splice-junction mutation responsible for familial apolipoprotein A-II deficiency. Am J Hum Genet. 1990;46:822\u2013827.","journal-title":"Am J Hum Genet"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2211023"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1715944"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2404143"}],"container-title":["Arteriosclerosis, Thrombosis, and Vascular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/ATVBAHA.124.322336","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T15:45:58Z","timestamp":1767714358000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/ATVBAHA.124.322336"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":56,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1161\/ATVBAHA.124.322336"],"URL":"https:\/\/doi.org\/10.1161\/atvbaha.124.322336","relation":{},"ISSN":["1079-5642","1524-4636"],"issn-type":[{"value":"1079-5642","type":"print"},{"value":"1524-4636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11]]},"assertion":[{"value":"2024-12-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}