Department of Epidemiology and Public Health, University College London, London, UK.
Heart. 2012 Apr;98(8):615-22. doi: 10.1136/heartjnl-2011-300862. Epub 2012 Mar 3.
Translational phases of study are important in evaluating whether a prognostic biomarker is likely to have impact on clinical practice but systematic evaluations of such evidence are lacking.
To systematically evaluate the clinical usefulness of the published literature on the association of natriuretic peptides (NP) and prognosis in stable coronary disease.
MEDLINE and EMBASE until the end of July 2009, without restrictions.
Prospective studies measuring NP in people with stable coronary disease who were followed-up for all cause mortality, coronary or cardiovascular events.
Two independent reviewers categorised studies according to the American Heart Association phase of study, and extracted data according to the study reporting guidelines from the American Heart Association and REMARK.
Systematic review of 19 studies found 17 which were phase 2, reporting an association between NP and events, two phase 3 studies, statistically examining the incremental prognostic value of NP, but no studies assessing whether NP predicted risk sufficiently to change management (phase 4), improve clinical outcomes (phase 5) or cost effectiveness (phase 6). No study referred to a statistical analytic protocol. Meta-analysis of 14 studies, reporting 18,841 patients and 1655 outcome events, found an RR for events of 3.28 (95% CI 2.45 to 4.38) comparing top versus bottom third of NP. This effect was 26% lower among the five studies which adjusted for a priori confounders (age, sex, renal function and left ventricular function) and 38% lower when adjusting for publication bias (Egger's p=0.001).
The unbiased strength of association of NP with prognosis in stable coronary disease is unclear, and there is a lack of reports of clinically useful measures of prediction and discrimination or studies relating NP levels to clinical decision making. The available literature is confined to early phases and is of limited clinical usefulness.
在评估预后生物标志物是否可能对临床实践产生影响时，研究的转化阶段很重要，但缺乏对这种证据的系统评价。
系统评价关于稳定型冠状动脉疾病中利钠肽（NP）与预后相关性的已发表文献的临床实用性。
MEDLINE 和 EMBASE，截至 2009 年 7 月底，无限制。
前瞻性研究，测量稳定型冠状动脉疾病患者 NP，随访所有原因死亡率、冠状动脉或心血管事件。
两名独立的审查员根据美国心脏协会的研究阶段对研究进行分类，并根据美国心脏协会和 REMARK 的研究报告指南提取数据。
对 19 项研究进行系统评价，发现其中 17 项为 2 期研究，报告 NP 与事件之间存在相关性，2 项 3 期研究，对 NP 的额外预后价值进行了统计学检验，但没有研究评估 NP 是否足以预测风险以改变治疗（第 4 阶段）、改善临床结局（第 5 阶段）或成本效益（第 6 阶段）。没有研究提到统计分析方案。对 14 项研究进行荟萃分析，报告 18841 例患者和 1655 例结局事件，发现 NP 最高与最低三分位相比，事件的 RR 为 3.28（95%CI 2.45 至 4.38）。在调整了预先设定的混杂因素（年龄、性别、肾功能和左心室功能）的五项研究中，这种影响降低了 26%，在调整了发表偏倚时（Egger's p=0.001）降低了 38%。
NP 与稳定型冠状动脉疾病预后之间的关联的无偏关联强度尚不清楚，并且缺乏关于预测和区分的临床有用措施的报告，或关于 NP 水平与临床决策的关系的研究。现有的文献仅限于早期阶段，临床实用性有限。
