title: Diagnostic and Prognostic Utility of Circulating Cytochrome c in Acute Myocardial Infarction.
abstract: BACKGROUND
  In contrast to cardiomyocyte necrosis, which can be quantified by cardiac troponin, functional cardiomyocyte impairment, including mitochondrial dysfunction, has escaped clinical recognition in acute myocardial infarction (AMI) patients.
  
  
  OBJECTIVE
  To investigate the diagnostic accuracy for AMI and prognostic prediction of in-hospital mortality of cytochrome c.
  
  
  RESULTS
  We prospectively assessed cytochrome c serum levels at hospital presentation in 2 cohorts: a diagnostic cohort of patients presenting with suspected AMI and a prognostic cohort of definite AMI patients. Diagnostic accuracy for AMI was the primary diagnostic end point, and prognostic prediction of in-hospital mortality was the primary prognostic end point. Serum cytochrome c had no diagnostic utility for AMI (area under the receiver-operating characteristics curve 0.51; 95% confidence intervals 0.44-0.58; P=0.76). Among 753 AMI patients in the prognostic cohort, cytochrome c was detectable in 280 (37%) patients. These patients had higher in-hospital mortality than patients with nondetectable cytochrome c (6% versus 1%; P<0.001). This result was mainly driven by the high mortality rate observed in ST-segment-elevation AMI patients with detectable cytochrome c, as compared with those with nondetectable cytochrome c (11% versus 1%; P<0.001). At multivariable analysis, cytochrome c remained a significant independent predictor of in-hospital mortality (odds ratio 3.0; 95% confidence interval 1.9-5.7; P<0.001), even after adjustment for major clinical confounders (odds ratio 4.01; 95% confidence interval 1.20-13.38; P=0.02).
  
  
  CONCLUSIONS
  Cytochrome c serum concentrations do not have diagnostic but substantial prognostic utility in AMI.
authors: From the Centro Cardiologico Monzino, I.R.C.C.S., University of Milan, Italy (G.M., N.C., V.M., M.M., M.T.S., F.V., A.B., A.L.B.); European Institute of Oncology, Milan, Italy (M.T., M.G., D.C., M.T.S., C.M.C.); and Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, Switzerland (J.B., M.K., R.T., T.N., T.R., K.W., S.S., N.K., Z.S., C.M.). giancarlo.marenzi@ccfm.it.
authors: Giancarlo
authors: G
authors: Marenzi
authors: From the Centro Cardiologico Monzino, I.R.C.C.S., University of Milan, Italy (G.M., N.C., V.M., M.M., M.T.S., F.V., A.B., A.L.B.); European Institute of Oncology, Milan, Italy (M.T., M.G., D.C., M.T.S., C.M.C.); and Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, Switzerland (J.B., M.K., R.T., T.N., T.R., K.W., S.S., N.K., Z.S., C.M.).
authors: Nicola
authors: N
authors: Cosentino
authors: From the Centro Cardiologico Monzino, I.R.C.C.S., University of Milan, Italy (G.M., N.C., V.M., M.M., M.T.S., F.V., A.B., A.L.B.); European Institute of Oncology, Milan, Italy (M.T., M.G., D.C., M.T.S., C.M.C.); and Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, Switzerland (J.B., M.K., R.T., T.N., T.R., K.W., S.S., N.K., Z.S., C.M.).
authors: Jasper
authors: J
authors: Boeddinghaus
authors: From the Centro Cardiologico Monzino, I.R.C.C.S., University of Milan, Italy (G.M., N.C., V.M., M.M., M.T.S., F.V., A.B., A.L.B.); European Institute of Oncology, Milan, Italy (M.T., M.G., D.C., M.T.S., C.M.C.); and Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, Switzerland (J.B., M.K., R.T., T.N., T.R., K.W., S.S., N.K., Z.S., C.M.).
authors: Mirella
authors: M
authors: Trinei
authors: From the Centro Cardiologico Monzino, I.R.C.C.S., University of Milan, Italy (G.M., N.C., V.M., M.M., M.T.S., F.V., A.B., A.L.B.); European Institute of Oncology, Milan, Italy (M.T., M.G., D.C., M.T.S., C.M.C.); and Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, Switzerland (J.B., M.K., R.T., T.N., T.R., K.W., S.S., N.K., Z.S., C.M.).
authors: Marco
authors: M
authors: Giorgio
authors: From the Centro Cardiologico Monzino, I.R.C.C.S., University of Milan, Italy (G.M., N.C., V.M., M.M., M.T.S., F.V., A.B., A.L.B.); European Institute of Oncology, Milan, Italy (M.T., M.G., D.C., M.T.S., C.M.C.); and Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, Switzerland (J.B., M.K., R.T., T.N., T.R., K.W., S.S., N.K., Z.S., C.M.).
authors: Valentina
authors: V
authors: Milazzo
authors: From the Centro Cardiologico Monzino, I.R.C.C.S., University of Milan, Italy (G.M., N.C., V.M., M.M., M.T.S., F.V., A.B., A.L.B.); European Institute of Oncology, Milan, Italy (M.T., M.G., D.C., M.T.S., C.M.C.); and Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, Switzerland (J.B., M.K., R.T., T.N., T.R., K.W., S.S., N.K., Z.S., C.M.).
authors: Marco
authors: M
authors: Moltrasio
authors: From the Centro Cardiologico Monzino, I.R.C.C.S., University of Milan, Italy (G.M., N.C., V.M., M.M., M.T.S., F.V., A.B., A.L.B.); European Institute of Oncology, Milan, Italy (M.T., M.G., D.C., M.T.S., C.M.C.); and Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, Switzerland (J.B., M.K., R.T., T.N., T.R., K.W., S.S., N.K., Z.S., C.M.).
authors: Daniela
authors: D
authors: Cardinale
authors: From the Centro Cardiologico Monzino, I.R.C.C.S., University of Milan, Italy (G.M., N.C., V.M., M.M., M.T.S., F.V., A.B., A.L.B.); European Institute of Oncology, Milan, Italy (M.T., M.G., D.C., M.T.S., C.M.C.); and Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, Switzerland (J.B., M.K., R.T., T.N., T.R., K.W., S.S., N.K., Z.S., C.M.).
authors: Maria Teresa
authors: MT
authors: Sandri
authors: From the Centro Cardiologico Monzino, I.R.C.C.S., University of Milan, Italy (G.M., N.C., V.M., M.M., M.T.S., F.V., A.B., A.L.B.); European Institute of Oncology, Milan, Italy (M.T., M.G., D.C., M.T.S., C.M.C.); and Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, Switzerland (J.B., M.K., R.T., T.N., T.R., K.W., S.S., N.K., Z.S., C.M.).
authors: Fabrizio
authors: F
authors: Veglia
authors: From the Centro Cardiologico Monzino, I.R.C.C.S., University of Milan, Italy (G.M., N.C., V.M., M.M., M.T.S., F.V., A.B., A.L.B.); European Institute of Oncology, Milan, Italy (M.T., M.G., D.C., M.T.S., C.M.C.); and Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, Switzerland (J.B., M.K., R.T., T.N., T.R., K.W., S.S., N.K., Z.S., C.M.).
authors: Alice
authors: A
authors: Bonomi
authors: From the Centro Cardiologico Monzino, I.R.C.C.S., University of Milan, Italy (G.M., N.C., V.M., M.M., M.T.S., F.V., A.B., A.L.B.); European Institute of Oncology, Milan, Italy (M.T., M.G., D.C., M.T.S., C.M.C.); and Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, Switzerland (J.B., M.K., R.T., T.N., T.R., K.W., S.S., N.K., Z.S., C.M.).
authors: Max
authors: M
authors: Kaech
authors: From the Centro Cardiologico Monzino, I.R.C.C.S., University of Milan, Italy (G.M., N.C., V.M., M.M., M.T.S., F.V., A.B., A.L.B.); European Institute of Oncology, Milan, Italy (M.T., M.G., D.C., M.T.S., C.M.C.); and Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, Switzerland (J.B., M.K., R.T., T.N., T.R., K.W., S.S., N.K., Z.S., C.M.).
authors: Raphael
authors: R
authors: Twerenbold
authors: From the Centro Cardiologico Monzino, I.R.C.C.S., University of Milan, Italy (G.M., N.C., V.M., M.M., M.T.S., F.V., A.B., A.L.B.); European Institute of Oncology, Milan, Italy (M.T., M.G., D.C., M.T.S., C.M.C.); and Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, Switzerland (J.B., M.K., R.T., T.N., T.R., K.W., S.S., N.K., Z.S., C.M.).
authors: Thomas
authors: T
authors: Nestelberger
authors: From the Centro Cardiologico Monzino, I.R.C.C.S., University of Milan, Italy (G.M., N.C., V.M., M.M., M.T.S., F.V., A.B., A.L.B.); European Institute of Oncology, Milan, Italy (M.T., M.G., D.C., M.T.S., C.M.C.); and Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, Switzerland (J.B., M.K., R.T., T.N., T.R., K.W., S.S., N.K., Z.S., C.M.).
authors: Tobias
authors: T
authors: Reichlin
authors: From the Centro Cardiologico Monzino, I.R.C.C.S., University of Milan, Italy (G.M., N.C., V.M., M.M., M.T.S., F.V., A.B., A.L.B.); European Institute of Oncology, Milan, Italy (M.T., M.G., D.C., M.T.S., C.M.C.); and Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, Switzerland (J.B., M.K., R.T., T.N., T.R., K.W., S.S., N.K., Z.S., C.M.).
authors: Karin
authors: K
authors: Wildi
authors: From the Centro Cardiologico Monzino, I.R.C.C.S., University of Milan, Italy (G.M., N.C., V.M., M.M., M.T.S., F.V., A.B., A.L.B.); European Institute of Oncology, Milan, Italy (M.T., M.G., D.C., M.T.S., C.M.C.); and Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, Switzerland (J.B., M.K., R.T., T.N., T.R., K.W., S.S., N.K., Z.S., C.M.).
authors: Samyut
authors: S
authors: Shrestha
authors: From the Centro Cardiologico Monzino, I.R.C.C.S., University of Milan, Italy (G.M., N.C., V.M., M.M., M.T.S., F.V., A.B., A.L.B.); European Institute of Oncology, Milan, Italy (M.T., M.G., D.C., M.T.S., C.M.C.); and Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, Switzerland (J.B., M.K., R.T., T.N., T.R., K.W., S.S., N.K., Z.S., C.M.).
authors: Nikola
authors: N
authors: Kohzuharov
authors: From the Centro Cardiologico Monzino, I.R.C.C.S., University of Milan, Italy (G.M., N.C., V.M., M.M., M.T.S., F.V., A.B., A.L.B.); European Institute of Oncology, Milan, Italy (M.T., M.G., D.C., M.T.S., C.M.C.); and Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, Switzerland (J.B., M.K., R.T., T.N., T.R., K.W., S.S., N.K., Z.S., C.M.).
authors: Zaid
authors: Z
authors: Sabti
authors: From the Centro Cardiologico Monzino, I.R.C.C.S., University of Milan, Italy (G.M., N.C., V.M., M.M., M.T.S., F.V., A.B., A.L.B.); European Institute of Oncology, Milan, Italy (M.T., M.G., D.C., M.T.S., C.M.C.); and Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, Switzerland (J.B., M.K., R.T., T.N., T.R., K.W., S.S., N.K., Z.S., C.M.).
authors: Carlo M
authors: CM
authors: Cipolla
authors: From the Centro Cardiologico Monzino, I.R.C.C.S., University of Milan, Italy (G.M., N.C., V.M., M.M., M.T.S., F.V., A.B., A.L.B.); European Institute of Oncology, Milan, Italy (M.T., M.G., D.C., M.T.S., C.M.C.); and Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, Switzerland (J.B., M.K., R.T., T.N., T.R., K.W., S.S., N.K., Z.S., C.M.).
authors: Christian
authors: C
authors: Mueller
authors: From the Centro Cardiologico Monzino, I.R.C.C.S., University of Milan, Italy (G.M., N.C., V.M., M.M., M.T.S., F.V., A.B., A.L.B.); European Institute of Oncology, Milan, Italy (M.T., M.G., D.C., M.T.S., C.M.C.); and Cardiovascular Research Institute Basel (CRIB) and Department of Cardiology, University Hospital Basel, Switzerland (J.B., M.K., R.T., T.N., T.R., K.W., S.S., N.K., Z.S., C.M.).
authors: Antonio L
authors: AL
authors: Bartorelli
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D045304:Cytochromes c / Q000097:blood*; D005260:Female; D017052:Hospital Mortality / Q000639:trends; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000175:diagnosis* / Q000401:mortality; D010343:Patient Admission / Q000639:trends; D011379:Prognosis; D011446:Prospective Studies
chemical_list: D015415:Biomarkers; D045304:Cytochromes c
keywords: acute myocardial infarction; cardiac troponin; cytochrome c; mitochondrial dysfunction; prognosis