Kaufman Center for Heart Failure Treatment and Recovery, Heart, Vascular and Thoracic Institute, Cleveland Clinic, Cleveland, Ohio.
Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
J Card Fail. 2021 Jun;27(6):670-676. doi: 10.1016/j.cardfail.2021.01.006. Epub 2021 Jan 23.
The inflammatory cytokine IL-6 has been previously implicated in the pathophysiology of acute decompensated heart failure (HF). Prior observations in acute HF patients have suggested that IL-6 may be associated with outcomes and modulated by nesiritide. We aimed to evaluate the associations between serial IL-6 measurements, mortality and rehospitalization in acute HF.
We analyzed the associations between IL-6 in acute HF, readmission, and mortality (30 and 180 days) using a cohort of 883 hospitalized patients from the ASCEND-HF trial (nesiritide vs placebo). Plasma IL-6 was measured at randomization (baseline), 48-72 hours, and 30 days. The median IL-6 was highest at baseline (14.1 pg/mL) and decreased at subsequent time points (7.6 pg/mL at 30 days). In a univariable Cox regression analysis, the baseline IL-6 was associated with 30- and 180-day mortality (hazard ratio per log 1.74, 95% confidence interval 1.09-2.78, P = .021; hazard ratio 3.23, confidence interval 1.18-8.86, P = .022, respectively). However, there was no association after multivariable adjustment. IL-6 at 48-72 hours was found to be independently associated with 30-day mortality (hazard ratio 8.2, confidence interval 1.2-57.5, P= .03), but not 180-day mortality in multivariable analysis that included the ASCEND-HF risk model and amino terminal pro-B-type natriuretic peptide as covariates. In comparison with placebo, nesiritide therapy was not associated with differences in serial IL-6 levels.
Although elevated IL-6 levels were associated with higher all-cause mortality in acute HF, no independent association with this outcome was identified at baseline or 30-day measurements. In contrast with prior reports, we did not observe any impact of nesiritide over placebo on serial IL-6 levels.
炎症细胞因子 IL-6 先前被认为与急性失代偿性心力衰竭（HF）的病理生理学有关。急性 HF 患者的先前观察结果表明，IL-6 可能与结局相关，并受奈西立肽调节。我们旨在评估急性 HF 患者中连续 IL-6 测量值与死亡率和再入院之间的关系。
我们使用 ASCEND-HF 试验（奈西立肽与安慰剂）的 883 名住院患者队列分析了急性 HF、再入院和死亡率（30 天和 180 天）之间的关系。在随机分组（基线）、48-72 小时和 30 天时测量血浆 IL-6。基线时 IL-6 中位数最高（14.1pg/mL），随后各时间点下降（30 天时 7.6pg/mL）。在单变量 Cox 回归分析中，基线 IL-6 与 30 天和 180 天死亡率相关（每对数 1.74 的风险比，95%置信区间 1.09-2.78，P=0.021；风险比 3.23，置信区间 1.18-8.86，P=0.022）。然而，在多变量调整后没有关联。48-72 小时的 IL-6 被发现与 30 天死亡率独立相关（风险比 8.2，置信区间 1.2-57.5，P=0.03），但在包括 ASCEND-HF 风险模型和氨基末端 pro-B 型利钠肽作为协变量的多变量分析中，与 180 天死亡率无关。与安慰剂相比，奈西立肽治疗与连续 IL-6 水平无差异。
尽管升高的 IL-6 水平与急性 HF 中的全因死亡率较高相关，但在基线或 30 天测量时，未发现与该结局的独立关联。与先前的报告不同，我们没有观察到奈西立肽与安慰剂相比对连续 IL-6 水平的任何影响。
