Elevation of tumor necrosis factor-α and increased risk of recurrent coronary events after myocardial infarction
Elevation of tumor necrosis factor-α and increased risk of recurrent coronary events after myocardial infarction
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DOI：
10.1161/01.cir.101.18.2149
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发表时间：
2000-05-09
期刊：
影响因子：
37.8
通讯作者：
Braunwald, E
中科院分区：
文献类型：
--
作者：
Ridker, PM;Rifai, N;Braunwald, E
背景-肿瘤坏死因子-α (TNF-α) 水平随急性缺血而增加。然而，心肌缺血 (MI) 后稳定期 TNF-α 的升高是否与复发冠状动脉事件的风险增加相关尚不清楚。 方法和结果 - 采用巢式病例对照设计来比较胆固醇和复发事件 (CARE) 试验中 272 名随后出现复发性冠状动脉事件的参与者在初始 MI 后 8.9 个月获得的平均 TNF-α 水平。 非致命性心梗或致命性心血管事件（病例），以及来自同等数量的年龄和性别匹配的参与者，他们在随访期间未发生这些事件（对照）。总体而言，病例中的 TNF-α 水平显着高于对照组（2.84 与 2.57 pg/mL，P=0.02）。 MT 后复发冠状动脉事件的额外风险主要见于 TNF-α 水平最高的患者，例如 TNF-α 水平超过 4.17 pg/mL（对照分布的第 95 个百分位数）的患者，风险增加约 3 倍（RR=2.7，95% CI 1.4 至 5.2，P=0.004）。风这些数据支持这样的假设：血管风险增加的稳定患者中存在持续的炎症不稳定性。因此，旨在减轻炎症的新疗法可能代表了心肌梗死治疗的新方向。
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.Methods and 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 MT 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 approximate to 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.