Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Department of Cardiology, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
Eur J Heart Fail. 2017 Oct;19(10):1310-1320. doi: 10.1002/ejhf.912. Epub 2017 Jun 21.
It is unclear whether distinct pathophysiological processes are present among patients with acute heart failure (AHF), with and without diabetes. Network analysis of biomarkers may identify correlative associations that reflect different pathophysiological pathways.
We analysed a panel of 48 circulating biomarkers measured within 24 h of admission for AHF in a subset of patients enrolled in the PROTECT trial. In patients with and without diabetes, we performed a network analysis to identify correlations between measured biomarkers. Compared with patients without diabetes (n = 1111), those with diabetes (n = 922) had a higher prevalence of ischaemic heart disease and traditional coronary risk factors. After multivariable adjustment, patients with and without diabetes had significantly different levels of biomarkers across a spectrum of pathophysiological domains, including inflammation (TNFR-1a, periostin), cardiomyocyte stretch (BNP), angiogenesis (VEGFR, angiogenin), and renal function (NGAL, KIM-1) (adjusted P-value <0.05). Among patients with diabetes, network analysis revealed that periostin strongly clustered with C-reactive protein and interleukin-6. Furthermore, renal markers (creatinine and NGAL) closely associated with potassium and glucose. These findings were not seen among patients without diabetes.
Patients with AHF and diabetes, compared with those without diabetes, have distinct biomarker profiles. Network analysis suggests that cardiac remodelling, inflammation, and fibrosis are closely associated with each other in patients with diabetes. Furthermore, potassium levels may be sensitive to changes in renal function as reflected by the strong renal-potassium-glucose correlation. These findings were not seen among patients without diabetes and may suggest distinct pathophysiological processes among AHF patients with diabetes.
目前尚不清楚伴有和不伴有糖尿病的急性心力衰竭（AHF）患者是否存在不同的病理生理过程。生物标志物的网络分析可能会识别出反映不同病理生理途径的相关关联。
我们分析了 PROTECT 试验中一部分入选患者入院 24 小时内测量的 48 种循环生物标志物的一个面板。在有和没有糖尿病的患者中，我们进行了网络分析，以确定测量的生物标志物之间的相关性。与没有糖尿病的患者（n=1111）相比，患有糖尿病的患者（n=922）有更高的缺血性心脏病和传统的冠状动脉危险因素患病率。在多变量调整后，有和没有糖尿病的患者在包括炎症（TNFR-1a、骨桥蛋白）、心肌细胞拉伸（BNP）、血管生成（VEGFR、血管生成素）和肾功能（NGAL、KIM-1）在内的一系列病理生理领域的生物标志物水平有显著差异（调整后的 P 值<0.05）。在糖尿病患者中，网络分析显示骨桥蛋白与 C 反应蛋白和白细胞介素 6 强烈聚类。此外，肾脏标志物（肌酐和 NGAL）与钾和葡萄糖密切相关。这些发现在没有糖尿病的患者中没有出现。
与没有糖尿病的患者相比，患有 AHF 和糖尿病的患者具有不同的生物标志物谱。网络分析表明，在糖尿病患者中，心脏重塑、炎症和纤维化彼此密切相关。此外，钾水平可能对肾功能变化敏感，这反映在肾脏-钾-葡萄糖的强烈相关性中。这些发现在没有糖尿病的患者中没有出现，可能表明糖尿病的 AHF 患者存在不同的病理生理过程。
