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  • Newman, Jonathan D.NYU, Grossman Sch Med, Dept Med, New York, NY USA.;NYU, Grossman Sch Med, Leon H Charney Div Cardiol, Translat Res Bldg, 227 E 30th St, Ste 853, New York, NY 10016 USA.;NYU, Ctr Prevent Cardiovasc Dis, Grossman Sch Med, Translat Res Bldg, 227 E 30th St, Ste 853, New York, NY 10016 USA. (author)

Biomarkers and cardiovascular events in patients with stable coronary disease in the ISCHEMIA Trials

  • Article/chapterEnglish2023

Publisher, publication year, extent ...

  • Elsevier,2023
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-524331
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-524331URI
  • https://doi.org/10.1016/j.ahj.2023.08.007DOI

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  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • ImportanceBiomarkers may improve prediction of cardiovascular events for patients with stable coronary artery disease (CAD), but their importance in addition to clinical tests of inducible ischemia and CAD severity is unknown.ObjectivesTo evaluate the prognostic value of multiple biomarkers in stable outpatients with obstructive CAD and moderate or severe inducible ischemia.Design and settingThe ISCHEMIA and ISCHEMIA CKD trials randomized 5,956 participants with CAD to invasive or conservative management from July 2012 to January 2018; 1,064 participated in the biorepository.Main outcome measuresPrimary outcome was cardiovascular death, myocardial infarction (MI), or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. Secondary outcome was cardiovascular death or MI. Improvements in prediction were assessed by cause-specific hazard ratios (HR) and area under the receiver operating characteristics curve (AUC) for an interquartile increase in each biomarker, controlling for other biomarkers, in a base clinical model of risk factors, left ventricular ejection fraction (LVEF) and ischemia severity. Secondary analyses were performed among patients in whom core-lab confirmed severity of CAD was ascertained by computed cardiac tomographic angiography (CCTA).ExposuresBaseline levels of interleukin-6 (IL-6), high sensitivity troponin T (hsTnT), growth differentiation factor 15 (GDF-15), N-terminal pro-B-type natriuretic peptide (NT-proBNP), lipoprotein a (Lp[a]), high sensitivity C-reactive protein (hsCRP), Cystatin C, soluble CD 40 ligand (sCD40L), myeloperoxidase (MPO), and matrix metalloproteinase 3 (MMP3).ResultsAmong 757 biorepository participants, median (IQR) follow-up was 3 (2-5) years, age was 67 (61-72) years, and 144 (19%) were female; 508 had severity of CAD by CCTA available. In an adjusted multimarker model with hsTnT, GDF-15, NT-proBNP and sCD40L, the adjusted HR for the primary outcome per interquartile increase in each biomarker was 1.58 (95% CI 1.22, 2.205), 1.60 (95% CI 1.16, 2.20), 1.61 (95% 1.22, 2.14), and 1.46 (95% 1.12, 1.90), respectively. The adjusted multimarker model also improved prediction compared with the clinical model, increasing the AUC from 0.710 to 0.792 (P < .01) and 0.714 to 0.783 (P < .01) for the primary and secondary outcomes, respectively. Similar findings were observed after adjusting for core-lab confirmed atherosclerosis severity.Conclusions and relevanceAmong ISCHEMIA biorepository participants, biomarkers of myocyte injury/distension, inflammation, and platelet activity improved cardiovascular event prediction in addition to risk factors, LVEF, and assessments of ischemia and atherosclerosis severity. These biomarkers may improve risk stratification for patients with stable CAD.

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  • Anthopolos, RebeccaNYU Langone Hlth, Div Biostat, Dept Populat Hlth, New York, NY USA. (author)
  • Ruggles, Kelly V.NYU, Grossman Sch Med, Dept Med, New York, NY USA. (author)
  • Cornwell, MacintoshNYU, Grossman Sch Med, Dept Med, New York, NY USA. (author)
  • Reynolds, Harmony R.NYU, Grossman Sch Med, Dept Med, New York, NY USA. (author)
  • Bangalore, SripalNYU, Grossman Sch Med, Dept Med, New York, NY USA. (author)
  • Mavromatis, KretonEmory Univ, Sch Med, Dept Med, Div Cardiol, Atlanta, GA USA. (author)
  • Held, Claes,1956-Uppsala universitet,Kardiologi(Swepub:uu)clahe947 (author)
  • Wallentin, Lars,1943-Uppsala universitet,Kardiologi(Swepub:uu)larswall (author)
  • Kullo, Iftikar J.Mayo Clin, Dept Cardiovasc Med, Rochester, MN USA. (author)
  • McManus, BruceUniv British Columbia, Dept Pathol & Lab Med, Vancouver, BC, Canada. (author)
  • Newby, L. Kristin K.Duke Clin Res Inst, Dept Med, Div Cardiol, Durham, NC USA. (author)
  • Rosenberg, YvesNatl Heart Lung & Blood Inst, Natl Inst Hlth, NIH, Bethesda, MD USA. (author)
  • Hochman, Judith S.NYU, Grossman Sch Med, Dept Med, New York, NY USA. (author)
  • Maron, David J.Stanford Univ, Dept Med, Stanford, CA USA. (author)
  • Berger, Jeffrey S.NYU, Grossman Sch Med, Dept Med, New York, NY USA. (author)
  • NYU, Grossman Sch Med, Dept Med, New York, NY USA.;NYU, Grossman Sch Med, Leon H Charney Div Cardiol, Translat Res Bldg, 227 E 30th St, Ste 853, New York, NY 10016 USA.;NYU, Ctr Prevent Cardiovasc Dis, Grossman Sch Med, Translat Res Bldg, 227 E 30th St, Ste 853, New York, NY 10016 USA.NYU Langone Hlth, Div Biostat, Dept Populat Hlth, New York, NY USA. (creator_code:org_t)

Related titles

  • In:American Heart Journal: Elsevier266, s. 61-730002-87031097-6744

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