The incremental prognostic and clinical value of multiple novel biomarkers in heart failure
The incremental prognostic and clinical value of multiple novel biomarkers in heart failure
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DOI：
10.1002/ejhf.543
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发表时间：
2016-12-01
影响因子：
18.2
通讯作者：
McMurray, John J. V.
中科院分区：
文献类型：
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作者：
Jackson, Colette E.;Haig, Caroline;McMurray, John J. V.
目标 近年来，心力衰竭 (HF) 的生物标志物数量有所增加。这些新型生物标志物组合的临床作用尚不清楚。 方法和结果 以下新型生物标志物是从最近住院的 628 名失代偿性心力衰竭患者中测定的；中区肾上腺髓质素原 (MR-proADM)、中区前心房钠尿肽 (MR-proANP)、和肽、高敏心肌肌钙蛋白 T (hs-cTnT)、ST2、半乳糖凝集素-3、胱抑素 C、组合游离轻链 (cFLC) 和高敏 C 反应蛋白 (hsCRP)。这些新型生物标志物的增量预后价值在包含已建立的死亡率预测因子的广泛模型中进行了评估。在平均 (SD) 3.2 (1.5) 年的随访期间，290 名 (46%) 患者死亡。所有新型生物标志物浓度的升高均与未经调整的死亡风险增加相关，但多变量分析后，只有三分之二是独立的预测因素。使用接受者操作特征分析的二分切点，MR-proADM、hs-cTnT、cFLC、hsCRP 和 ST2 仍然是死亡率的独立预测因子。进一步二分为低风险组（0-2 个生物标志物升高）或高风险组（5 个生物标志物中至少有 3 个升高）提供了最大的增量预后价值（风险比 2.20，95% 置信区间 1.37-3.54；P = 0.001），并改善了模型的性能（C 统计量从 0.721 变为 0.730，净重分类指数 32.5%）。 结论本研究中包含的新型生物标志物本身对包含已建立的死亡率预测因子的模型几乎没有增加任何增量预后价值。然而，在二分法之后，五种新型生物标志物提供了增量的预后价值。随着新型生物标志物数量的增加，死亡风险存在明显的梯度，至少存在三名确定死亡风险最高的患者。
Aims In recent years there has been an increase in the number of biomarkers in heart failure (HF). The clinical role for these novel biomarkers in combination is not clear.Methods and results The following novel biomarkers were measured from 628 patients recently hospitalized with decompensated HF; mid-regional pro-adrenomedullin (MR-proADM), mid-regional pro-atrial natriuretic peptide (MR-proANP), copeptin, high-sensitivity cardiac troponin T (hs-cTnT), ST2, galectin-3, cystatin C, combined free light chains (cFLC) and high sensitivity C-reactive protein (hsCRP). The incremental prognostic value of these novel biomarkers was evaluated within an extensive model containing established predictors of mortality. During a mean (SD) follow-up of 3.2 (1.5) years, 290 (46%) patients died. Elevated concentrations of all novel biomarkers were associated with an increased unadjusted risk of mortality but only two-thirds were independent predictors following multivariable analysis. Using dichotomized cut-points from receiver operating characteristic analysis, MR-proADM, hs-cTnT, cFLC, hsCRP, and ST2 remained independent predictors of mortality. Further dichotomization into low (0-2 elevated biomarkers) or high (at least three of the five biomarkers elevated) risk groups provided greatest incremental prognostic value (hazard ratio 2.20, 95% confidence interval 1.37-3.54; P = 0.001) and improved the performance of the model (C-statistic 0.730 from 0.721, net reclassification index 32.5%).Conclusion The novel biomarkers included in this study added little, if any, incremental prognostic value on their own to a model containing established predictors of mortality. However, following dichotomization, five of the novel biomarkers provided incremental prognostic value. There was a clear gradient in the risk of death with increasing numbers of elevated novel biomarkers, with the presence of at least three identifying patients at greatest risk of mortality.