Department of Cardiology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
Sphingotec GmbH, Hennigsdorf, Germany.
Eur J Heart Fail. 2019 Jun;21(6):732-743. doi: 10.1002/ejhf.1437. Epub 2019 Mar 6.
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.
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 = 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.
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.
肾上腺髓质素（ADM）的分泌受容量超负荷刺激以维持内皮屏障功能，心力衰竭（HF）中生物活性（bio-）ADM 水平升高是对血管渗漏和组织水肿的拮抗反应。本研究旨在确定血浆生物活性 ADM 作为 HF 恶化患者充血标志物的价值。
在 BIOSTAT-CHF 中纳入 2179 例新发或恶化 HF 患者，研究了血浆生物活性 ADM 与充血临床标志物的相关性及其预后价值。在另外的 1703 例患者队列中验证了数据。血浆生物活性 ADM 水平较高的患者年龄较大，HF 更严重，充血的体征和症状更多（均 P<0.001）。在 20 种生物标志物中，生物活性 ADM 是充血临床评分的最强预测因子（r=0.198）。多变量回归分析显示，生物活性 ADM 与较高的体重指数、更多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，生物活性 ADM 与水肿、端坐呼吸、啰音、肝肿大和颈静脉压聚类。较高的生物活性 ADM 与血管紧张素转换酶抑制剂/血管紧张素受体阻滞剂 3 个月后上调剂量不足独立相关，但与β受体阻滞剂无关。较高的生物活性 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）。验证队列中的分析得出了类似的结果。
新发和恶化 HF 患者的血浆生物活性 ADM 与更严重的 HF 和更多的水肿、端坐呼吸、肝肿大和颈静脉压相关。因此，我们推测生物活性 ADM 是充血标志物，可能有助于指导充血治疗。
