Berger Martin, März Winfried, Niessner Alexander, Delgado Graciela, Kleber Marcus, Scharnagl Hubert, Marx Nikolaus, Schuett Katharina
Department of Internal Medicine I; University Hospital Aachen, RWTH University, Aachen, Germany.
Medical Clinic V (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology) Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany.
ESC Heart Fail. 2024 Dec;11(6):3607-3615. doi: 10.1002/ehf2.14959. Epub 2024 Jul 14.
Inflammation accompanies heart failure (HF) and elevated levels of inflammatory biomarkers are linked to new onset of HF. However, whether the prognostic relevance of inflammatory biomarkers is different in HF with reduced (HFrEF) and preserved ejection fraction (HFpEF) is unclear. The aim of the current study is to explore the role of inflammation on the mortality risk in patients with HF.
We analysed interleukin-6 and hsCRP levels by ELISA and immunonephelometry, respectively, in HFpEF and HFrEF patients referred for coronary angiography and assessed the prognostic value in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study.
HF was present in 1086 patients (N = 506 HFpEF; N = 580 HFrEF; mean age 65 ± 10 years; 28% female). Increasing IL-6 levels were significantly associated with increased CV mortality in HFpEF [1.5 (95% CI: 1.1-2.2), P = 0.018] but not HFrEF [HR 1.3 (95% CI: 1.0-1.7), P = 0.06] patients. High-sensitive CRP followed a similar pattern but failed to reach statistical significance after full-adjustment (HFpEF: HR 1.4 95%C I: 1.0-2.0; P = 0.065; HFrEF HR: 1.0 95% CI: 0.7-1.3; P = 0.800). Interaction analysis in patients stratified by IL-6 and N terminal pro brain natriuretic peptide (NT-proBNP) above and below the median revealed a stepwise increase in CV-mortality in HFpEF (P = 0.036) but not HFrEF patients (P = 0.220). To investigate the relationship between IL-6 and NT-proBNP, we assessed the genetic IL6-Receptor variant p.Asp358Ala (rs2228145) which is linked to impaired IL-6 receptor signalling. Homozygous carriers with HFpEF but not HFrEF exhibited significantly lower NT-pro-BNP levels compared with wildtype carriers (HFpEF 779 pg/mL ± 787 vs. 1180 pg/ mL ± 1532; P = 0.008; HFrEF 2289 pg/ mL ± 3439 vs. 2326 pg/ mL ± 3386; P = 0.94), raising the hypothesis that IL-6 signalling may play a pathophysiological role in HFpEF.
These data suggest a predictive value of elevated IL-6 for CV-mortality in HFpEF but not in HFrEF patients.
炎症伴随心力衰竭（HF），炎症生物标志物水平升高与HF的新发有关。然而，炎症生物标志物的预后相关性在射血分数降低的心力衰竭（HFrEF）和射血分数保留的心力衰竭（HFpEF）中是否不同尚不清楚。本研究的目的是探讨炎症在HF患者死亡风险中的作用。
我们分别通过酶联免疫吸附测定法（ELISA）和免疫比浊法分析了因冠状动脉造影而转诊的HFpEF和HFrEF患者的白细胞介素-6（IL-6）和超敏C反应蛋白（hsCRP）水平，并在路德维希港风险与心血管健康（LURIC）研究中评估了其预后价值。
1086例患者存在HF（N = 506例HFpEF；N = 580例HFrEF；平均年龄65±10岁；28%为女性）。IL-6水平升高与HFpEF患者心血管死亡率增加显著相关[1.5（95%置信区间：1.1-2.2），P = 0.018]，但与HFrEF患者无关[风险比（HR）1.3（95%置信区间：1.0-1.7），P = 0.06]。高敏CRP呈现类似模式，但在完全调整后未达到统计学显著性（HFpEF：HR 1.4，95%置信区间：1.0-2.0；P = 0.065；HFrEF HR：1.0，95%置信区间：0.7-1.3；P = 0.800）。对IL-6和N末端脑钠肽前体（NT-proBNP）高于和低于中位数进行分层的患者进行交互分析显示，HFpEF患者心血管死亡率呈逐步上升趋势（P = 0.036），而HFrEF患者则无此趋势（P = 0.220）。为了研究IL-6与NT-proBNP之间的关系，我们评估了与IL-6受体信号传导受损相关的基因IL6受体变体p.Asp358Ala（rs2228145）。与野生型携带者相比，HFpEF的纯合子携带者而非HFrEF的纯合子携带者NT-pro-BNP水平显著降低（HFpEF：779 pg/mL±787 vs. 1180 pg/mL±1532；P = 0.008；HFrEF：2289 pg/mL±3439 vs. 2326 pg/mL±3386；P = 0.94），这提出了IL-6信号传导可能在HFpEF中发挥病理生理作用的假设。
这些数据表明，IL-6升高对HFpEF患者的心血管死亡率具有预测价值，但对HFrEF患者则无此价值。
