Division of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden
Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
J Am Heart Assoc. 2018 Apr 23;7(9):e008299. doi: 10.1161/JAHA.117.008299.
We aimed to assess the associations and predictive powers between the soluble receptors for tumor necrosis factor (TNF)-α (TNFR1 and TNFR2) and cardiovascular outcomes in patients with stable coronary heart disease.
CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) is a randomized clinical trial comparing clarithromycin with placebo in patients with stable coronary heart disease. The primary outcome was a composite of nonfatal acute myocardial infarction, unstable angina pectoris, cerebrovascular disease, and all-cause mortality. Patients were followed up for 10 years; discovery sample, those assigned placebo (1204 events in n=1998); and replication sample, those assigned clarithromycin (1220 events in n=1979). We used Cox regression adjusted for C-reactive protein level, established cardiovascular risk factors, kidney function, and cardiovascular drugs. After adjustments, higher serum levels of TNFR1 and TNFR2 were associated with the composite outcome in the discovery sample (hazard ratio per SD increase, 1.13; 95% confidence interval, 1.05-1.22; =0.001 for TNFR1; hazard ratio, 1.16; 95% confidence interval, 1.08-1.24; <0.001 for TNFR2). The associations were similar in the replication sample. The associations with the composite outcome were mainly driven by acute myocardial infarction, cardiovascular mortality, and noncardiovascular mortality. The addition of TNFR1 and TNFR2 to established cardiovascular risk factors improved prediction only modestly (<1%).
Increased concentrations of circulating TNFR1 and TNFR2 were associated with increased risks of cardiovascular events and mortality in patients with stable coronary heart disease. Yet, the utility of measuring TNFR1 and TNFR2 to improve risk prediction in these patients appears limited.
URL: https://www.clinicaltrials.gov. Unique identifier: NCT00121550.
我们旨在评估可溶性肿瘤坏死因子（TNF）-α受体（TNFR1 和 TNFR2）与稳定型冠心病患者心血管结局之间的关联和预测能力。
CLARICOR（克拉霉素对缺血性心脏病患者死亡率和发病率的影响）是一项比较稳定型冠心病患者克拉霉素与安慰剂的随机临床试验。主要结局是复合终点，包括非致死性急性心肌梗死、不稳定型心绞痛、脑血管病和全因死亡率。患者随访 10 年；发现样本为接受安慰剂的患者（1998 例中有 1204 例事件）；复制样本为接受克拉霉素的患者（1979 例中有 1220 例事件）。我们使用 Cox 回归调整 C 反应蛋白水平、已确立的心血管危险因素、肾功能和心血管药物。调整后，发现血清中 TNFR1 和 TNFR2 水平升高与发现样本中的复合结局相关（每标准差增加的危险比，1.13；95%置信区间，1.05-1.22；TNFR1 为 0.001；危险比，1.16；95%置信区间，1.08-1.24；TNFR2 为<0.001）。在复制样本中也存在相似的关联。与复合结局相关的主要是急性心肌梗死、心血管死亡率和非心血管死亡率。将 TNFR1 和 TNFR2 添加到已确立的心血管危险因素中，只能适度改善预测（<1%）。
循环中 TNFR1 和 TNFR2 浓度升高与稳定型冠心病患者心血管事件和死亡率增加相关。然而，测量 TNFR1 和 TNFR2 以改善这些患者的风险预测的效用似乎有限。
