Elevation of Tumor Necrosis Factor-α and Increased Risk of Recurrent Coronary Events After Myocardial Infarction

TLDR

TNF‑α levels rise during acute ischemia, but it is unclear whether persistent elevations after myocardial infarction predict subsequent coronary events. The study aimed to determine whether elevated TNF‑α during the stable phase after MI is associated with an increased risk of recurrent coronary events. A nested case‑control analysis of 272 CARE trial participants measured TNF‑α 8.9 months post‑MI and compared levels between those who later experienced recurrent events and matched controls. Higher TNF‑α levels were found in cases versus controls, with individuals above the 95th percentile experiencing roughly a three‑fold increase in recurrent coronary event risk, independent of other risk factors.

Abstract

Background —Levels of tumor necrosis factor-α (TNF-α) increase with acute ischemia. However, whether elevations of TNF-α 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-α 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-α 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-α, 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-α 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.