Bratseth Vibeke, Nendl Andraz, Raju Sajan C, Holm Kristian, Broch Kaspar, Hov Johannes R, Seljeflot Ingebjørg, Trøseid Marius, Awoyemi Ayodeji
Oslo Center for Clinical Heart Research, Department of Cardiology Ullevaal, Oslo University Hospital, Oslo, Norway.
Oslo Center for Clinical Heart Research, Department of Cardiology Ullevaal, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
Int J Cardiol. 2025 Jan 15;419:132689. doi: 10.1016/j.ijcard.2024.132689. Epub 2024 Nov 1.
Chronic heart failure (HF) patients have reduced microbiota diversity. Leakage of microbes and their metabolites into the bloodstream may activate neutrophils. Neutrophil extracellular traps (NETs) consist of chromatin and proteases, and may contribute to HF pathogenesis. We assessed associations between circulating NETs and 1) cardiac function, 2) the degree of gut microbiota diversity and 3) gut leakage and microbial metabolites in HF patients.
A cross-sectional study including 124 patients with chronic HF and left ventricular ejection fraction ≤40 %. Severe HF was defined as N-terminal pro-B-type natriuretic peptide concentrations above median. We measured citrullinated histone H (CitH), myeloperoxidase- and double-stranded-DNA in the blood. Gut leakage markers included bacterial lipopolysaccharides and soluble cluster of differentiation 14. The microbial metabolites included circulating trimethylamine N-oxide and butyrate producing capacity. We used the Shannon diversity-index and a dysbiosis-index based on bacteria with altered relative abundance to characterize the gut microbiota profile.
Quartile 4 of CitH was associated with more severe HF compared to quartiles 1-3, after adjustments for age, gender and hypertension (adjusted odds ratio [95 %CI] 3.21[1.18-8.69], p = 0.022). CitH was moderately associated with hypertension (p = 0.04), higher CRP levels (p = 0.016) and lower Shannon diversity index (p = 0.039). No other NET marker associated with severe HF.
In chronic HF patients with reduced LVEF, high levels of CitH were associated with disease severity, inflammation and reduced gut microbiota diversity. Our results suggest that enhanced release of NETs could be involved in progressive HF, although the contribution of the gut microbiota seems limited in this context.
慢性心力衰竭（HF）患者的微生物群多样性降低。微生物及其代谢产物漏入血液可能会激活中性粒细胞。中性粒细胞胞外诱捕网（NETs）由染色质和蛋白酶组成，可能参与HF的发病机制。我们评估了循环NETs与1）心功能、2）肠道微生物群多样性程度以及3）HF患者肠道渗漏和微生物代谢产物之间的关联。
一项横断面研究，纳入124例慢性HF且左心室射血分数≤40%的患者。重度HF定义为N末端B型利钠肽前体浓度高于中位数。我们检测了血液中的瓜氨酸化组蛋白H（CitH）、髓过氧化物酶和双链DNA。肠道渗漏标志物包括细菌脂多糖和可溶性分化簇14。微生物代谢产物包括循环三甲胺N-氧化物和丁酸盐产生能力。我们使用香农多样性指数和基于相对丰度改变的细菌的失调指数来表征肠道微生物群特征。
在调整年龄、性别和高血压后，与第1-3四分位数相比，CitH的第4四分位数与更严重的HF相关（调整后的优势比[95%CI]为3.21[1.18-8.69]，p = 0.022）。CitH与高血压（p = 0.04）、较高的CRP水平（p = 0.016）和较低的香农多样性指数（p = 0.039）中度相关。没有其他NET标志物与重度HF相关。
在左心室射血分数降低的慢性HF患者中，高水平的CitH与疾病严重程度、炎症和肠道微生物群多样性降低相关。我们的结果表明，NETs释放增加可能参与了HF的进展，尽管在这种情况下肠道微生物群的作用似乎有限。
