From the VA Medical Center, Minneapolis, MN (I.S.A., T.S.R., M.K.); University of Minnesota, Minneapolis (I.A.S., T.S.R., M.K., J.N.C.); and Critical Diagnostics, San Diego, CA (J.S.).
Circ Heart Fail. 2014 May;7(3):418-26. doi: 10.1161/CIRCHEARTFAILURE.113.001036. Epub 2014 Mar 12.
Soluble ST2 (sST2), a biomarker related to inflammation, is associated with outcomes of patients with heart failure. In-depth analyses of the relationship among sST2, changes in sST2, and patient outcomes are reported.
sST2 was measured at baseline (n=1650), 4 months (n=1345), and 12 months (n=1094) in Valsartan Heart Failure Trial. Baseline sST2 averaged 28.7±16.2 ng/mL, significantly (P<0.001) higher in men than women but supranormal in only 9% and 15%, respectively. A continuous relationship between sST2 and the log hazard ratio for outcomes was modeled as 2 linear segments with a significant decrease in the rate of increase in hazard ratios >33.2 ng/mL. Each segment of the sST2 distribution was significantly (P<0.0001) associated with the risks of morbid event, mortality, and hospitalization for heart failure. Only sST2 values <33.2 ng/mL were significantly related to the outcomes when 23 readily available clinical variables including N-terminal probrain natriuretic peptide were included in the Cox regression model. sST2 did not improve discrimination of patient outcomes. Compared with placebo, valsartan significantly (P<0.001) reduced the rate of increase in sST2. Increases in sST2 for 12 months, but not decreases, were significantly associated with subsequent outcomes, independent of clinical variables, sST2, and valsartan treatment.
In this study, baseline sST2 was nonlinearly associated with patient outcomes but did not provide substantial prognostic information when added to a clinical prediction model that included N-terminal probrain natriuretic peptide. An increase but not decrease in sST2 was independently associated with outcomes. Additional research is needed to determine whether monitoring ST2 levels can improve patient outcomes.
可溶性 ST2（sST2）是一种与炎症相关的生物标志物，与心力衰竭患者的预后相关。本研究深入分析了 sST2、sST2 变化与患者预后之间的关系。
在缬沙坦心力衰竭试验中，分别于基线（n=1650）、4 个月（n=1345）和 12 个月（n=1094）时测量 sST2。基线 sST2 平均值为 28.7±16.2ng/mL，男性显著高于女性（P<0.001），但仅分别有 9%和 15%的患者 sST2 水平高于正常值上限。sST2 与结局的对数风险比之间呈连续关系，可建模为 2 个线性段，sST2 水平每增加 33.2ng/mL，风险比的增长率显著下降。sST2 分布的每个段均与不良事件、死亡率和心力衰竭住院风险显著相关（P<0.0001）。仅当 Cox 回归模型中包含 23 个易于获得的临床变量（包括 N 末端脑利钠肽前体）时，sST2 值<33.2ng/mL 才与结局显著相关。sST2 并未改善患者结局的判别能力。与安慰剂相比，缬沙坦显著降低了 sST2 的增长率（P<0.001）。sST2 增加 12 个月，但不是减少，与随后的结局显著相关，独立于临床变量、sST2 和缬沙坦治疗。
在这项研究中，基线 sST2 与患者预后呈非线性相关，但当添加包括 N 末端脑利钠肽前体的临床预测模型时，并未提供实质性的预后信息。sST2 增加而非减少与结局独立相关。需要进一步研究以确定监测 ST2 水平是否可以改善患者结局。
