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

Abstract

MD; for the Cholesterol And Recurrent Events (CARE) InvestigatorsBackground-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, Pϭ0.02). 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 Ϸ3-fold increase in risk (RRϭ2.7, 95% CI 1.4 to 5.2, Pϭ0.004). Risk estimates were independent of other risk factors and were similar in subgroup analyses limited to cardiovascular death (RRϭ2.1) or to recurrent nonfatal MI (RRϭ3.2). 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

Relation of circulating interleukin‐6 to left ventricular remodeling in patients with reperfused anterior myocardial infarction

“…6,7 Previous clinical studies have indicated the presence of activated circulating leukocytes and inflammatory cytokines, as well as acute-phase reactants such as CRP in patients with AMI. 13,14,19 In particular, it has been shown that elevated CRP levels and monocytosis are associated with LV enlargement and aneurysm after reperfused MI, suggesting an important role of inflammatory response in post-infarct remodeling. 8,9 The monocyte-related cytokines, such as IL-6, stimulate liver cells to produce CRP and lead to peripheral monocytosis.…”

“…11,12 In addition, clinical studies have demonstrated the presence of increased circulating levels of proinflammatory cytokines in patients with AMI. 13,14 These cytokines can stimulate fibroblast proliferation and collagen deposition and may be involved in apoptosis, which is proposed as an important mechanism in postinfarct remodeling. 15,16 In view of these results, it is apparent that proinflammatory cytokines play an important role in the reperfused myocardium during the remodeling process.…”

Dual role of infections as risk factors for coronary heart disease

“…This mechanism might be mediated by cytokines such as interleukin-6 [26] and tumor necrosis factor α [27,28]. Our recent experimental studies have shown a profound and diffuse impairment of endothelial function of coronary vascular bed during acute C. pneumoniae infection in piglets [23].…”

A randomized, controlled trial of the effects of rosiglitazone on adipokines, and inflammatory and fibrinolytic markers in diabetic patients: Study design and protocol

“…protein (CRP), interleukin-6 (IL-6), tumour necrosis factor-alpha and markers of endothelial dysfunction have been shown to be independent predictors of both diabetes and cardiovascular risk (6,(8)(9)(10). Furthermore, inhibition of fibrinolysis, which is attributable to elevated concentrations of plasminogen activator inhibitor type 1 (PAI-1), is associated with insulin resistance and type 2 diabetes, and predicts myocardial infarction and stroke (11,12).…”