title: Elevation of tumor necrosis factor-alpha and increased risk of recurrent coronary events after myocardial infarction.
abstract: BACKGROUND
  Levels of tumor necrosis factor-alpha (TNF-alpha) increase with acute ischemia. However, whether elevations of TNF-alpha in the stable phase after myocardial ischemia (MI) are associated with increased risk of recurrent coronary events is unknown.
  
  
  RESULTS
  A nested case-control design was used to compare TNF-alpha levels obtained an average of 8.9 months after initial MI among 272 participants in the Cholesterol And Recurrent Events (CARE) trial who subsequently developed recurrent nonfatal MI or a fatal cardiovascular event (cases) and from an equal number of age- and sex-matched participants who remained free of these events during follow-up (controls). Overall, TNF-alpha levels were significantly higher among cases than controls (2.84 versus 2.57 pg/mL, P=0.02). The excess risk of recurrent coronary events after MI was predominantly seen among those with the highest levels of TNF-alpha, such that those with levels in excess of 4.17 pg/mL (the 95th percentile of the control distribution) had an approximately 3-fold increase in risk (RR=2.7, 95% CI 1.4 to 5.2, P=0.004). Risk estimates were independent of other risk factors and were similar in subgroup analyses limited to cardiovascular death (RR=2.1) or to recurrent nonfatal MI (RR=3.2).
  
  
  CONCLUSIONS
  Plasma concentrations of TNF-alpha are persistently elevated among post-MI patients at increased risk for recurrent coronary events. These data support the hypothesis that a persistent inflammatory instability is present among stable patients at increased vascular risk. Novel therapies designed to attenuate inflammation may thus represent a new direction in the treatment of MI.
authors.affiliation: Leducq Center for Molecular and Genetic Epidemiology of Cardiovascular Disorders, Brigham's and Women's Hospital, Boston, MA 02115, USA.
authors.forename: P M
authors.initials: PM
authors.lastname: Ridker
authors.forename: N
authors.initials: N
authors.lastname: Rifai
authors.forename: M
authors.initials: M
authors.lastname: Pfeffer
authors.forename: F
authors.initials: F
authors.lastname: Sacks
authors.forename: S
authors.initials: S
authors.lastname: Lepage
authors.forename: E
authors.initials: E
authors.lastname: Braunwald
mesh_terms: D000328:Adult; D000368:Aged; D003327:Coronary Disease / Q000097:blood / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000503:physiopathology*; D011237:Predictive Value of Tests; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D014409:Tumor Necrosis Factor-alpha