PMID- 37604357
OWN - NLM
STAT- MEDLINE
DCOM- 20231120
LR  - 20240207
IS  - 1097-6744 (Electronic)
IS  - 0002-8703 (Print)
IS  - 0002-8703 (Linking)
VI  - 266
DP  - 2023 Dec
TI  - Biomarkers and cardiovascular events in patients with stable coronary disease in 
      the ISCHEMIA Trials.
PG  - 61-73
LID - S0002-8703(23)00204-1 [pii]
LID - 10.1016/j.ahj.2023.08.007 [doi]
AB  - IMPORTANCE: Biomarkers 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. 
      OBJECTIVES: To evaluate the prognostic value of multiple biomarkers in stable 
      outpatients with obstructive CAD and moderate or severe inducible ischemia. 
      DESIGN AND SETTING: The 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 MEASURES: 
      Primary 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). EXPOSURES: Baseline 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). RESULTS: 
      Among 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 
      RELEVANCE: Among 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.
CI  - Copyright (c) 2023 Elsevier Inc. All rights reserved.
FAU - Newman, Jonathan D
AU  - Newman JD
AD  - Department of Medicine, NYU Grossman School of Medicine, New York, NY. Electronic 
      address: Jonathan.Newman@nyumc.org.
FAU - Anthopolos, Rebecca
AU  - Anthopolos R
AD  - Division of Biostatistics, Department of Population Health, NYU Langone Health, 
      New York, NY.
FAU - Ruggles, Kelly V
AU  - Ruggles KV
AD  - Department of Medicine, NYU Grossman School of Medicine, New York, NY.
FAU - Cornwell, Macintosh
AU  - Cornwell M
AD  - Department of Medicine, NYU Grossman School of Medicine, New York, NY.
FAU - Reynolds, Harmony R
AU  - Reynolds HR
AD  - Department of Medicine, NYU Grossman School of Medicine, New York, NY.
FAU - Bangalore, Sripal
AU  - Bangalore S
AD  - Department of Medicine, NYU Grossman School of Medicine, New York, NY.
FAU - Mavromatis, Kreton
AU  - Mavromatis K
AD  - Division of Cardiology, Department of Medicine, Emory University School of 
      Medicine, Atlanta, GA.
FAU - Held, Claes
AU  - Held C
AD  - Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden.
FAU - Wallentin, Lars
AU  - Wallentin L
AD  - Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden.
FAU - Kullo, Iftikar J
AU  - Kullo IJ
AD  - Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN.
FAU - McManus, Bruce
AU  - McManus B
AD  - Department of Pathology and Laboratory Medicine, University of British Columbia, 
      Vancouver, British Columbia, Canada.
FAU - Newby, L Kristin K
AU  - Newby LKK
AD  - Division of Cardiology, Department of Medicine, Duke Clinical Research Institute, 
      Durham, NC.
FAU - Rosenberg, Yves
AU  - Rosenberg Y
AD  - Division of Cardiovascular Sciences, National Health Lung and Blood Institute, 
      National Institute of Health, Bethesda, MD.
FAU - Hochman, Judith S
AU  - Hochman JS
AD  - Department of Medicine, NYU Grossman School of Medicine, New York, NY.
FAU - Maron, David J
AU  - Maron DJ
AD  - Department of Medicine, Stanford University, Stanford, CA.
FAU - Berger, Jeffrey S
AU  - Berger JS
AD  - Department of Medicine, NYU Grossman School of Medicine, New York, NY.
CN  - ISCHEMIA Biorepository Research Group
LA  - eng
GR  - UL1 TR001445/TR/NCATS NIH HHS/United States
GR  - R01 HL165208/HL/NHLBI NIH HHS/United States
GR  - U01 HL105462/HL/NHLBI NIH HHS/United States
GR  - U01 HL105907/HL/NHLBI NIH HHS/United States
GR  - U01 HL105565/HL/NHLBI NIH HHS/United States
GR  - UL1 TR002243/TR/NCATS NIH HHS/United States
GR  - U01 HL105561/HL/NHLBI NIH HHS/United States
GR  - R56 HL155528/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20230819
PL  - United States
TA  - Am Heart J
JT  - American heart journal
JID - 0370465
RN  - 0 (Growth Differentiation Factor 15)
RN  - 0 (Biomarkers)
RN  - 114471-18-0 (Natriuretic Peptide, Brain)
RN  - 0 (Peptide Fragments)
SB  - IM
MH  - Humans
MH  - Female
MH  - Aged
MH  - Male
MH  - *Coronary Artery Disease/diagnosis
MH  - Growth Differentiation Factor 15
MH  - Stroke Volume
MH  - Ventricular Function, Left
MH  - Biomarkers
MH  - *Myocardial Infarction
MH  - Prognosis
MH  - *Atherosclerosis
MH  - Natriuretic Peptide, Brain
MH  - Peptide Fragments
PMC - PMC10843480
MID - NIHMS1931299
OTO - NOTNLM
OT  - Biomarkers
OT  - Coronary atherosclerosis
OT  - ISCHEMIA trial
OT  - Inducible ischemia
OT  - Risk prediction
OT  - Stable coronary artery disease
EDAT- 2023/08/22 00:41
MHDA- 2023/11/20 06:54
PMCR- 2024/12/01
CRDT- 2023/08/21 19:30
PHST- 2023/08/16 00:00 [received]
PHST- 2023/08/16 00:00 [accepted]
PHST- 2024/12/01 00:00 [pmc-release]
PHST- 2023/11/20 06:54 [medline]
PHST- 2023/08/22 00:41 [pubmed]
PHST- 2023/08/21 19:30 [entrez]
AID - S0002-8703(23)00204-1 [pii]
AID - 10.1016/j.ahj.2023.08.007 [doi]
PST - ppublish
SO  - Am Heart J. 2023 Dec;266:61-73. doi: 10.1016/j.ahj.2023.08.007. Epub 2023 Aug 19.