(Circulation. 2000;101:2149.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Elevation of Tumor Necrosis Factor-
and Increased Risk of Recurrent Coronary Events After Myocardial Infarction
From the Leducq Center for Molecular and Genetic Epidemiology of Cardiovascular Disorders (P.M.R.), the Center for Cardiovascular Prevention (P.M.R.), Division of Cardiovascular Diseases (P.M.R., M.P., F.S., E.B.) and the Division of Preventive Medicine (P.M.R.), Brigham and Women’s Hospital; the Department of Pathology, Children’s Hospital Medical Center (N.R.), Harvard Medical School, Boston, Mass; and the Centre Universitaire de Sante de l’Estrie (S.L.), Sherbrooke, Quebec, Canada.
Correspondence to Dr Paul M. Ridker, Cardiovascular Diseases, Brigham and Women’s Hospital, 75 Francis St, Boston, MA 02115.
Background—Levels of tumor
necrosis factor-
(TNF-) increase with acute ischemia.
However, whether elevations of TNF- in the stable phase after
myocardial ischemia (MI) are associated with increased risk of
recurrent coronary events is unknown.
Methods and Results—A nested case-control design was used to
compare TNF- 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- 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-, such that those with levels in excess of 4.17 pg/mL
(the 95th percentile of the control distribution) had an 
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- 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.
Key Words: inflammation • myocardial infarction • tumor necrosis factor • atherosclerosis
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