Bio-adrenomedullin as a marker of congestion in patients with new-onset and worsening heart failure
Bio-adrenomedullin as a marker of congestion in patients with new-onset and worsening heart failure
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DOI：
10.1002/ejhf.1437
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发表时间：
2019-06-01
影响因子：
18.2
通讯作者：
Voors, Adriaan A.
中科院分区：
文献类型：
--
作者：
ter Maaten, Jozine M.;Kremer, Daan;Voors, Adriaan A.
背景容量超负荷刺激肾上腺髓质素（ADM）分泌以维持内皮屏障功能，心力衰竭（HF）中较高水平的生物活性（生物）ADM是对血管渗漏和组织水肿的抵消反应。本研究旨在确定血浆bio-ADM作为心力衰竭恶化患者充血标志物的价值。方法和结果在BIOSTAT-CHF中登记的2179例新发或恶化的HF患者中研究了血浆bio-ADM与充血临床标志物的相关性及其预后价值。在一个单独的1703例患者队列中验证了数据。血浆bio-ADM水平较高的患者年龄较大，HF更严重，充血症状和体征更多（均P < 0.001）。在20种生物标志物中，bio-ADM是临床充血评分的最强预测因子（r（2）= 0.198）。在多变量回归分析中，较高的bio-ADM与较高的体重指数，更多的水肿和较高的成纤维细胞生长因子23相关。在分层聚类分析中，生物ADM与水肿、端坐呼吸、罗音、肝肿大和颈静脉压聚类。较高的bio-ADM与3个月后血管紧张素转换酶抑制剂/血管紧张素受体阻滞剂的剂量上调受损独立相关，但与β受体阻滞剂无关。较高的bio-ADM水平与全因死亡率和HF住院风险增加独立相关（风险比1.16，95%置信区间1.06-1.27，P = 0.002，每对数增加）。验证队列的分析得出了类似的结果。结论血浆bio-ADM水平与心衰加重、水肿、端坐呼吸、肝肿大及颈静脉压增高有关。因此，我们假设生物ADM作为充血标记物，这可能有助于指导缓解治疗。
Background Secretion of adrenomedullin (ADM) is stimulated by volume overload to maintain endothelial barrier function, and higher levels of biologically active (bio-) ADM in heart failure (HF) are a counteracting response to vascular leakage and tissue oedema. This study aimed to establish the value of plasma bio-ADM as a marker of congestion in patients with worsening HF. Methods and results The association of plasma bio-ADM with clinical markers of congestion, as well as its prognostic value was studied in 2179 patients with new-onset or worsening HF enrolled in BIOSTAT-CHF. Data were validated in a separate cohort of 1703 patients. Patients with higher plasma bio-ADM levels were older, had more severe HF and more signs and symptoms of congestion (all P < 0.001). Amongst 20 biomarkers, bio-ADM was the strongest predictor of a clinical congestion score (r(2) = 0.198). In multivariable regression analysis, higher bio-ADM was associated with higher body mass index, more oedema, and higher fibroblast growth factor 23. In hierarchical cluster analysis, bio-ADM clustered with oedema, orthopnoea, rales, hepatomegaly and jugular venous pressure. Higher bio-ADM was independently associated with impaired up-titration of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers after 3 months, but not of beta-blockers. Higher bio-ADM levels were independently associated with an increased risk of all-cause mortality and HF hospitalization (hazard ratio 1.16, 95% confidence interval 1.06-1.27, P = 0.002, per log increase). Analyses in the validation cohort yielded comparable findings. Conclusions Plasma bio-ADM in patients with new-onset and worsening HF is associated with more severe HF and more oedema, orthopnoea, hepatomegaly and jugular venous pressure. We therefore postulate bio-ADM as a congestion marker, which might become useful to guide decongestive therapy.