Elevation of tumor necrosis factor-alpha and increased risk of recurrent coronary events after myocardial infarction.
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.
Ridker
P M
PM
Leducq Center for Molecular and Genetic Epidemiology of Cardiovascular Disorders, Brigham's and Women's Hospital, Boston, MA 02115, USA.
Rifai
N
N
Pfeffer
M
M
Sacks
F
F
Lepage
S
S
Braunwald
E
E
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
D014409:Tumor Necrosis Factor-alpha