title: Subclinical myocardial necrosis and cardiovascular risk in stable patients undergoing elective cardiac evaluation.
abstract: OBJECTIVE
  The presence of subclinical myocardial necrosis as a prodrome to longer-term adverse cardiac event risk has been debated. The debate has focused predominantly within patients with acute coronary syndrome, and on issues of troponin assay variability and accuracy of detection, rather than on the clinical significance of the presence of subclinical myocardial necrosis (ie, "troponin leak") within stable cardiac patients. Herein, we examine the relationship between different degrees of subclinical myocardial necrosis and long-term adverse clinical outcomes within a stable cardiac patient population with essentially normal renal function.
  
  
  RESULTS
  Sequential consenting patients (N=3828; median creatinine clearance, 100 mL/min/1.73m(2)) undergoing elective diagnostic coronary angiography with cardiac troponin I (cTnI) levels below the diagnostic cut-off for defining myocardial infarction (<0.03 ng/mL) were evaluated. The relationship of subclinical myocardial necrosis with incident major adverse cardiovascular events (defined as any death, myocardial infarction, or stroke) over 3-year follow-up was examined. "Probable" (cTnI 0.001-0.008 ng/mL) and "definite" (cTnI 0.009-0.029 ng/mL) subclinical myocardial necrosis were observed frequently within the cohort (34% and 18%, respectively). A linear relationship was observed between the magnitude of subclinical myocardial necrosis and risk of 3-year incident major adverse cardiovascular events, particularly in those with cTnI 0.009 ng/mL or higher (hazard ratio, 3.00; 95% confidence interval, 2.4-3.8), even after adjustment for traditional risk factors, C-reactive protein, and creatinine clearance. The presence of subclinical myocardial necrosis was associated with elevations in acute phase proteins (C-reactive protein, ceruloplasmin; P<0.01 each) and reduction in systemic antioxidant enzyme activities (arylesterase; P<0.01) but showed no significant associations with multiple specific measures of oxidant stress, and showed borderline associations with myeloperoxidase, a marker of leukocyte activation.
  
  
  CONCLUSIONS
  In stable cardiology patients, prodromal subclinical myocardial necrosis is associated with substantially higher long-term risk for major adverse cardiovascular events. The underlying mechanisms contributing to this minimal troponin leak phenomenon warrants further investigation.
authors.affiliation: Department of Cardiovascular Medicine, Heart & Vascular Institute, Cleveland Clinic, 9500 Euclid Avenue, Desk J3-4, Cleveland, OH 44195, USA. tangw@ccf.org
authors.forename: W H Wilson
authors.initials: WH
authors.lastname: Tang
authors.forename: Yuping
authors.initials: Y
authors.lastname: Wu
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Nicholls
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Brennan
authors.forename: Michael
authors.initials: M
authors.lastname: Pepoy
authors.forename: Shirley
authors.initials: S
authors.lastname: Mann
authors.forename: Alan
authors.initials: A
authors.lastname: Pratt
authors.forename: Frederick
authors.initials: F
authors.lastname: Van Lente
authors.forename: Stanley L
authors.initials: SL
authors.lastname: Hazen
mesh_terms: D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D002265:Carboxylic Ester Hydrolases / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology*; D015331:Cohort Studies; D017023:Coronary Angiography; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology*; D009336:Necrosis; D012307:Risk Factors; D019210:Troponin I / Q000097:blood
chemical_list: D019210:Troponin I; D002097:C-Reactive Protein; D002265:Carboxylic Ester Hydrolases; C019734:arylesterase