Circulation: Cardiovascular Genetics HCG Simultaneous Consideration of Multiple Candidate Protein Biomarkers for Long-Term Risk for Cardiovascular Events Multiple Proteins Associated with Death/MI & Death CIRCCVG/2013/000490-T CIRCCVG/2013/000490-T 10.1161/CIRCGENETICS.113.000490 8 02/17/15 1 Sine Kristina 617-542-5100 617-542-6539 de Lemos, James UT Southwestern Medical Center Dr. L. Kristin Newby kristin.newby@duke.edu Dr. Duke University P.O. Box 17969 Durham North Carolina 27710 UNITED STATES na-na na-na 16763 Sharif Halim Duke University Medical Center sharif.halim@dm.duke.edu 169300 Megan Neely Duke Clinical Research institute megan.neely@duke.edu 99874 Karen S Pieper Duke Clinical Research Institute karen.pieper@duke.edu 67370 Svati H. Shah Duke University svati.shah@duke.edu 79894 William E. Kraus Duke University william.kraus@duke.edu 17132 Elizabeth R. Hauser Duke University elizabeth.hauser@duke.edu 5436 Robert M. Califf Duke Translational Medicine Institute, Duke University Medical Center, Durham, NC calif001@mc.duke.edu 13188 Christopher B. Granger Duke University christopher.granger@duke.edu 56045 L. Kristin Newby Duke University kristin.newby@duke.edu 16763 10/02/2013 10/02/2013 09/11/2014 10/06/2014 11/25/2014 02/17/2015 Original Article <P><B><I>Background</I></B>—Although individual protein biomarkers are associated with cardiovascular risk, rarely have multiple proteins been considered simultaneously to identify which set of proteins best predicts risk. </P><P><B><I>Methods and Results</I></B>—In a nested case-control study of 273 death/myocardial infarction (MI) cases and 273 age- (within 10 years), sex-, and race-matched and event-free controls from among 2023 consecutive patients (median follow-up 2.5 years) with suspected coronary disease, plasma levels of 53 previously reported biomarkers of cardiovascular risk were determined in a core laboratory. Three penalized logistic regression models were fit using the elastic net to identify panels of proteins independently associated with death/MI: proteins alone (Model 1); proteins in a model constrained to retain clinical variables (Model 2); and proteins and clinical variables available for selection (Model 3). Model 1 identified 6 biomarkers strongly associated with death/MI: ICAM-1, MMP-3, NT-proBNP, IL-6, sCD40L, and IGFBP2. In Model 2, only sCD40L remained strongly associated with death/MI when all clinical risk predictors were retained. Model 3 identified a set of 6 biomarkers (ICAM-1, MMP-3, NT-proBNP, IL-6, sCD40L, and IGFBP2) and 5 clinical variables (age, red-cell distribution width, diabetes, hemoglobin, and New York Heart Association class) strongly associated with death/MI. </P><P><B><I>Conclusions</I></B>—Simultaneously assessing the association between multiple putative protein biomarkers of cardiovascular risk and clinical outcomes is useful in identifying relevant biomarker panels for further assessment.</P> 6 0 0 0 0 yes CircGenetics_CIRCCVG-2013-000490-T.xml 000490_clinical perspective.docx CircGenetics_CIRCCVG-2013-000490-T_file1.docx CircGenetics_CIRCCVG-2013-000490-T_supp2.pdf CircGenetics_CIRCCVG-2013-000490-T_supp3.pdf CircGenetics_CIRCCVG-2013-000490-T_merge.pdf CircGenetics_CIRCCVG-2013-000490-T_Shah_79894_disclosure.pdf CircGenetics_CIRCCVG-2013-000490-T_Shah_79894_copyright.pdf CircGenetics_CIRCCVG-2013-000490-T_Hauser_5436_disclosure.pdf CircGenetics_CIRCCVG-2013-000490-T_Hauser_5436_copyright.pdf CircGenetics_CIRCCVG-2013-000490-T_Newby_16763_disclosure.pdf CircGenetics_CIRCCVG-2013-000490-T_Newby_16763_copyright.pdf CircGenetics_CIRCCVG-2013-000490-T_Neely_99874_disclosure.pdf CircGenetics_CIRCCVG-2013-000490-T_Neely_99874_copyright.pdf CircGenetics_CIRCCVG-2013-000490-T_Kraus_17132_disclosure.pdf CircGenetics_CIRCCVG-2013-000490-T_Kraus_17132_copyright.pdf CircGenetics_CIRCCVG-2013-000490-T_Granger_56045_disclosure.pdf CircGenetics_CIRCCVG-2013-000490-T_Granger_56045_copyright.pdf CircGenetics_CIRCCVG-2013-000490-T_Halim_169300_disclosure.pdf CircGenetics_CIRCCVG-2013-000490-T_Halim_169300_copyright.pdf CircGenetics_CIRCCVG-2013-000490-T_Califf_13188_disclosure.pdf CircGenetics_CIRCCVG-2013-000490-T_Califf_13188_copyright.pdf CircGenetics_CIRCCVG-2013-000490-T_Pieper_67370_disclosure.pdf CircGenetics_CIRCCVG-2013-000490-T_Pieper_67370_copyright.pdf Bill authors $70 per pg; no excess pgs. Article has supplemental material (1 PDF) and a clinical perspective. no figures Guest Editor for this article was James de Lemos, MD Article will have editorial by T. Wang #000973 Rec'd 10/2/13 (Invited from Circulation) Please set the flag 'exportcadmusahafundingtypecodes' with the funding type code of the sources you wish to list. Subject Codes: [135] Risk factors [144] Other arteriosclerosis [4] Acute myocardial infarction ksine