TIMI Study Group, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Clin Chem. 2012 Jan;58(1):257-66. doi: 10.1373/clinchem.2011.173369. Epub 2011 Nov 17.
We investigated the prognostic performance of ST2 with respect to cardiovascular death (CVD) and heart failure (HF) in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) in a large multinational trial.
Myocytes that are subjected to mechanical stress secrete ST2, a soluble interleukin-1 receptor family member that is associated with HF after STE-ACS.
We measured ST2 with a high-sensitivity assay in all available baseline samples (N=4426) in patients enrolled in the Metabolic Efficiency With Ranolazine for Less Ischemia in the Non-ST-Elevation Acute Coronary Syndrome Thrombolysis in Myocardial Infarction 36 (MERLIN-TIMI 36), a placebo-controlled trial of ranolazine in NSTE-ACS. All events, including cardiovascular death and new or worsening HF, were adjudicated by an independent events committee.
Patients with ST2 concentrations in the top quartile (>35 μg/L) were more likely to be older and male and have diabetes and renal dysfunction. ST2 was only weakly correlated with troponin and B-type natriuretic peptide. High ST2 was associated with increased risk for CVD/HF at 30 days (6.6% vs 1.6%, P<0.0001) and 1 year (12.2% vs 5.2%, P<0.0001). The risk associated with ST2 was significant after adjustment for clinical covariates and biomarkers (adjusted hazard ratio CVD/HF 1.90, 95% CI 1.15-3.13 at 30 days, P=0.012; 1.51, 95% CI 1.15-1.98 at 1 year, P=0.003), with a significant integrated discrimination improvement (P<0.0001). No significant interaction was found between ST2 and ranolazine (Pinteraction=0.15).
ST2 correlates weakly with biomarkers of acute injury and hemodynamic stress but is strongly associated with the risk of HF after NSTE-ACS. This biomarker and related pathway merit further investigation as potential therapeutic targets for patients with ACS at risk for cardiac remodeling.
我们在一项大型多国试验中研究了 ST2 与非 ST 段抬高型急性冠状动脉综合征（NSTE-ACS）患者心血管死亡（CVD）和心力衰竭（HF）的预后关系。
遭受机械应激的心肌细胞会分泌 ST2，这是一种白细胞介素 1 受体家族成员，与 STE-ACS 后的 HF 有关。
我们在 ranolazine 安慰剂对照 NSTE-ACS 试验 MERLIN-TIMI 36 中，用高敏检测法测量了所有可用基线样本（N=4426）中的 ST2。该试验评估了 ranolazine 在 NSTE-ACS 中的疗效。所有事件，包括心血管死亡和新发或恶化 HF，均由独立事件委员会裁定。
ST2 浓度处于四分位区间最高的患者（>35μg/L）年龄较大、男性、有糖尿病和肾功能不全。ST2 与肌钙蛋白和 B 型利钠肽仅有弱相关性。高 ST2 与 30 天（6.6%比 1.6%，P<0.0001）和 1 年（12.2%比 5.2%，P<0.0001）时 CVD/HF 风险增加相关。在调整临床协变量和生物标志物后，ST2 与风险相关仍然显著（30 天时 CVD/HF 的调整危险比为 1.90，95%CI 1.15-3.13，P=0.012；1 年时为 1.51，95%CI 1.15-1.98，P=0.003），并显著提高了综合判别改善（P<0.0001）。未发现 ST2 与 ranolazine 之间存在显著交互作用（Pinteraction=0.15）。
ST2 与急性损伤和血液动力学应激的生物标志物弱相关，但与 NSTE-ACS 后 HF 的风险密切相关。该生物标志物和相关途径值得进一步研究，以作为 ACS 患者心脏重构风险的潜在治疗靶点。
