title: Interaction of impaired coronary flow reserve and cardiomyocyte injury on adverse cardiovascular outcomes in patients without overt coronary artery disease.
abstract: BACKGROUND
  Minimally elevated serum cardiac troponin reflects myocardial injury and is associated with increased mortality, even absent coronary artery disease (CAD). We sought to investigate the relationship between low-level troponin elevation and impaired coronary flow reserve (CFR), an integrated measure of coronary vasomotor function, and to assess their contributions to adverse outcomes in patients without overt CAD.
  
  
  RESULTS
  Consecutive patients (n=761) undergoing evaluation for suspected CAD with troponin before stress myocardial perfusion positron emission tomography were followed up (median, 2.8 years) for major adverse cardiovascular events, including cardiovascular death, nonfatal myocardial infarction, or late revascularization. Patients with flow-limiting CAD, left ventricular ejection fraction <40%, or revascularization within 60 days of imaging were excluded. CFR was quantified from stress/rest myocardial blood flow with the use of positron emission tomography. Compared with patients with negative troponin, those with at least 1 positive troponin (n=97) had higher pretest clinical scores, more renal dysfunction, and lower left ventricular ejection fraction and CFR. In adjusted analysis, impaired CFR remained independently associated with positive troponin (odds ratio, 2.18; 95% confidence interval, 1.37-3.47; P=0.001), and both impaired CFR and positive troponin were independently associated with major adverse cardiovascular events (hazard ratio, 2.25; 95% confidence interval, 1.31-3.86; P=0.003; and hazard ratio, 2.42; 95% confidence interval, 1.34-4.40; P=0.004, respectively). Impaired CFR and positive troponin identified patients at highest risk of major adverse cardiovascular events (log-rank P<0.0001), with a significant interaction (P<0.007) seen between CFR and troponin.
  
  
  CONCLUSIONS
  In patients without overt CAD, impaired CFR was independently associated with minimally elevated troponin and major adverse cardiovascular events. Impaired CFR, here reflecting microvascular dysfunction, modified the effect of a positive troponin on adverse outcomes.
authors.affiliation: From the Noninvasive Cardiovascular Imaging Program, Heart and Vascular Institute, Division of Cardiovascular Medicine, Department of Medicine, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (V.R.T., M.G., C.R.F., J.H., R.B., S.D., M.F.D.C.); Center for Cardiovascular Disease Prevention, Division of Preventive Medicine, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (B.M.E.); and Divisions of Nuclear Medicine, Cardiothoracic Imaging, and Cardiovascular Medicine, Departments of Medicine and Radiology, University of Michigan, Ann Arbor (V.L.M.).
authors.forename: Viviany R
authors.initials: VR
authors.lastname: Taqueti
authors.affiliation: From the Noninvasive Cardiovascular Imaging Program, Heart and Vascular Institute, Division of Cardiovascular Medicine, Department of Medicine, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (V.R.T., M.G., C.R.F., J.H., R.B., S.D., M.F.D.C.); Center for Cardiovascular Disease Prevention, Division of Preventive Medicine, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (B.M.E.); and Divisions of Nuclear Medicine, Cardiothoracic Imaging, and Cardiovascular Medicine, Departments of Medicine and Radiology, University of Michigan, Ann Arbor (V.L.M.).
authors.forename: Brendan M
authors.initials: BM
authors.lastname: Everett
authors.affiliation: From the Noninvasive Cardiovascular Imaging Program, Heart and Vascular Institute, Division of Cardiovascular Medicine, Department of Medicine, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (V.R.T., M.G., C.R.F., J.H., R.B., S.D., M.F.D.C.); Center for Cardiovascular Disease Prevention, Division of Preventive Medicine, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (B.M.E.); and Divisions of Nuclear Medicine, Cardiothoracic Imaging, and Cardiovascular Medicine, Departments of Medicine and Radiology, University of Michigan, Ann Arbor (V.L.M.).
authors.forename: Venkatesh L
authors.initials: VL
authors.lastname: Murthy
authors.affiliation: From the Noninvasive Cardiovascular Imaging Program, Heart and Vascular Institute, Division of Cardiovascular Medicine, Department of Medicine, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (V.R.T., M.G., C.R.F., J.H., R.B., S.D., M.F.D.C.); Center for Cardiovascular Disease Prevention, Division of Preventive Medicine, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (B.M.E.); and Divisions of Nuclear Medicine, Cardiothoracic Imaging, and Cardiovascular Medicine, Departments of Medicine and Radiology, University of Michigan, Ann Arbor (V.L.M.).
authors.forename: Mariya
authors.initials: M
authors.lastname: Gaber
authors.affiliation: From the Noninvasive Cardiovascular Imaging Program, Heart and Vascular Institute, Division of Cardiovascular Medicine, Department of Medicine, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (V.R.T., M.G., C.R.F., J.H., R.B., S.D., M.F.D.C.); Center for Cardiovascular Disease Prevention, Division of Preventive Medicine, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (B.M.E.); and Divisions of Nuclear Medicine, Cardiothoracic Imaging, and Cardiovascular Medicine, Departments of Medicine and Radiology, University of Michigan, Ann Arbor (V.L.M.).
authors.forename: Courtney R
authors.initials: CR
authors.lastname: Foster
authors.affiliation: From the Noninvasive Cardiovascular Imaging Program, Heart and Vascular Institute, Division of Cardiovascular Medicine, Department of Medicine, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (V.R.T., M.G., C.R.F., J.H., R.B., S.D., M.F.D.C.); Center for Cardiovascular Disease Prevention, Division of Preventive Medicine, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (B.M.E.); and Divisions of Nuclear Medicine, Cardiothoracic Imaging, and Cardiovascular Medicine, Departments of Medicine and Radiology, University of Michigan, Ann Arbor (V.L.M.).
authors.forename: Jon
authors.initials: J
authors.lastname: Hainer
authors.affiliation: From the Noninvasive Cardiovascular Imaging Program, Heart and Vascular Institute, Division of Cardiovascular Medicine, Department of Medicine, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (V.R.T., M.G., C.R.F., J.H., R.B., S.D., M.F.D.C.); Center for Cardiovascular Disease Prevention, Division of Preventive Medicine, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (B.M.E.); and Divisions of Nuclear Medicine, Cardiothoracic Imaging, and Cardiovascular Medicine, Departments of Medicine and Radiology, University of Michigan, Ann Arbor (V.L.M.).
authors.forename: Ron
authors.initials: R
authors.lastname: Blankstein
authors.affiliation: From the Noninvasive Cardiovascular Imaging Program, Heart and Vascular Institute, Division of Cardiovascular Medicine, Department of Medicine, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (V.R.T., M.G., C.R.F., J.H., R.B., S.D., M.F.D.C.); Center for Cardiovascular Disease Prevention, Division of Preventive Medicine, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (B.M.E.); and Divisions of Nuclear Medicine, Cardiothoracic Imaging, and Cardiovascular Medicine, Departments of Medicine and Radiology, University of Michigan, Ann Arbor (V.L.M.).
authors.forename: Sharmila
authors.initials: S
authors.lastname: Dorbala
authors.affiliation: From the Noninvasive Cardiovascular Imaging Program, Heart and Vascular Institute, Division of Cardiovascular Medicine, Department of Medicine, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (V.R.T., M.G., C.R.F., J.H., R.B., S.D., M.F.D.C.); Center for Cardiovascular Disease Prevention, Division of Preventive Medicine, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA (B.M.E.); and Divisions of Nuclear Medicine, Cardiothoracic Imaging, and Cardiovascular Medicine, Departments of Medicine and Radiology, University of Michigan, Ann Arbor (V.L.M.). mdicarli@partners.org.
authors.forename: Marcelo F
authors.initials: MF
authors.lastname: Di Carli
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D015897:Comorbidity; D003324:Coronary Artery Disease / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology / Q000503:physiopathology*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D053805:Fractional Flow Reserve, Myocardial; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000453:epidemiology*; D009204:Myocardial Revascularization; D016016:Proportional Hazards Models; D018570:Risk Assessment; D013318:Stroke Volume; D016896:Treatment Outcome; D014336:Troponin / Q000097:blood*
chemical_list: D015415:Biomarkers; D014336:Troponin
keywords: coronary artery disease; microcirculation; positron emission tomography; troponin