Relationship between interleukin 6 and mortality in patients with unstable coronary artery disease - Effects of an early invasive or noninvasive strategy
Relationship between interleukin 6 and mortality in patients with unstable coronary artery disease - Effects of an early invasive or noninvasive strategy
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DOI：
10.1001/jama.286.17.2107
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发表时间：
2001-11-07
影响因子：
120.7
通讯作者：
Siegbahn, A
中科院分区：
文献类型：
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作者：
Lindmark, E;Diderholm, E;Siegbahn, A
背景 炎症活动与不稳定冠状动脉疾病 (CAD) 的长期死亡率高相关。白细胞介素 6 (IL-6) 诱导 C 反应蛋白和纤维蛋白原（炎症的全身标志物）。目的 确定 IL-6 的血浆水平是否可以预测死亡率，并评估不稳定 CAD 患者中 IL-6 水平与侵入性治疗与无创治疗策略的相互作用。设计、设置和患者 冠状动脉疾病不稳定期间的前瞻性随机法安明和快速血运重建 II 试验，在 3489 名患者、3269 名患者中进行1996 年 6 月至 1998 年 8 月间，在斯堪的纳维亚地区的 58 家医院对其中 10 名被诊断为不稳定 CAD 的患者进行了血浆样本 IL-6 水平分析（67% 为男性，中位年龄为 67 岁）。 干预措施 患者被随机分配接受早期侵入性治疗（n = 1222）或非侵入性治疗策略（n = 1235）。较胖组以及 666 名有侵入性治疗禁忌症的患者进一步随机接受为期 90 天的低分子肝素治疗（达肝素，5000-7500 IU，每天两次，n = 1140）或安慰剂（n = 1127）。主要结果测量药物和干预随机队列中 6 个月和 12 个月时的死亡率，结果 血浆 IL-6 水平至少为 5 ng/L 与低于 5 ng/L 的水平相比，在非侵入性治疗组（7.9% vs 2.3%；相对风险 [RR]，3.47；95% 置信区间 [CI]，1.94-6.21）和安慰剂治疗组（7.9% vs 2.3%）与死亡率大幅增加相关。 2.5%；RR，3.19；95% CI，1.77-5.74）。在对大多数既定风险指标进行调整后，这种关联仍然显着。早期侵入性治疗策略显着降低了 IL-6 水平升高患者的 12 个月死亡率（绝对降低 5.1%；P=0.004），而 IL-6 浓度不升高的患者死亡率并未降低。服用达肝素且 IL-6 水平升高的患者 6 个月死亡率低于未服用达肝素的患者（绝对降低 3.5%；P=0.08）。 结论 循环 IL-6 是不稳定 CAD 死亡率增加的一个强有力的独立标志物，可确定从早期侵入性治疗策略中获益最多的患者。
Context Inflammatory activity is associated with high rates of long-term mortality in unstable coronary artery disease (CAD). Interleukin 6 (IL-6) induces C-reactive protein and fibrinogen, systemic markers of inflammation.Objectives To determine whether plasma levels of IL-6 are predictive of mortality and to evaluate the interaction of IL-6 levels with the effects of invasive vs noninvasive treatment strategies in unstable CAD patients.Design, Setting, and Patients The prospective, randomized Fragmin and Fast Revascularisation During Instability in Coronary Artery Disease II trial, conducted among 3489 patients, 3269 of whom had plasma samples analyzed for IL-6 levels, with diagnosed unstable CAD (67% male, median age, 67 years) at 58 Scandinavian hospitals between June 1996 and August 1998.Interventions Patients were randomly assigned to receive either an early invasive (n = 1222) or a noninvasive treatment strategy (n = 1235). The fatter group, as well as 666 patients with contraindications to invasive therapy, were further randomized to 90-day treatment with low-molecular-weight heparin (dalteparin, 5000-7500 IU twice per day, n = 1140) or placebo (n = 1127).Main Outcome Measure Mortality at 6 and 12 months in the medically and interventionally randomized cohorts, respectively, in relation to IL-6 levels, measured at randomization.Results Plasma levels of IL-6 that were at least 5 ng/L compared with levels lower than 5 ng/L were associated with greatly increased mortality in the noninvasive group (7.9% vs 2.3%; relative risk [RR], 3.47; 95% confidence interval [CI], 1.94-6.21) and in the placebo-treated group (7.9% vs 2.5%; RR, 3.19; 95% CI, 1.77-5.74). The association remained significant after adjustment for most established risk indicators. An early invasive treatment strategy strongly reduced 12-month mortality among those with elevated IL-6 levels (5.1% absolute reduction; P=.004) whereas mortality was not reduced among patients without elevated IL-6 concentrations. Those taking dalteparin with elevated IL-6 levels experienced lower 6-month mortality than those who did not take dalteparin (3.5% absolute reduction; P=.08).Conclusions Circulating IL-6 is a strong independent marker of increased mortality in unstable CAD and identifies patients who benefit most from a strategy of early invasive management.