Association of Multiple Biomarkers With Risk of All-Cause and Cause-Specific Mortality After Acute Coronary Syndromes A Secondary Analysis of the PLATO Biomarker Study
Association of Multiple Biomarkers With Risk of All-Cause and Cause-Specific Mortality After Acute Coronary Syndromes A Secondary Analysis of the PLATO Biomarker Study
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DOI：
10.1001/jamacardio.2018.3811
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发表时间：
2018-12-01
期刊：
影响因子：
24
通讯作者：
Wallentin, Lars
中科院分区：
文献类型：
--
作者：
Lindholm, Daniel;James, Stefan K.;Wallentin, Lars
急性冠脉综合征事件后一年内的重要死亡率保持在5%左右。以前的研究已经评估了与全因或心血管死亡有关的生物标记物，但不是针对多个原因。目的评估不同的生物标记物是否提供了关于全因死亡和原因特定死亡的风险信息。设计、设置和参与者血小板抑制和患者结局(PLATO)试验从2006年10月到2008年7月随机选择了18624名急性冠状动脉综合征患者服用替卡格雷或氯吡格雷。在这项二次分析生物标志物亚研究中，17095名患者参与了这项二次分析生物标志物亚研究。主要结果和衡量死亡原因的是心肌梗死、心力衰竭、心源性猝死/心律失常、出血、手术、其他血管原因和非血管原因，以及全因死亡。研究对象为基线、血清胱抑素-C、生长分化因子-15(GDF-15)、高敏C反应蛋白、高敏肌钙蛋白I和T，以及N末端B型利钠肽(NT-proBNP)。结果患者的中位年龄为62.0(四分位数范围)。在17095例患者中，782例(4.6%)在随访期间死亡。生物标志物与全因死亡率和特定原因死亡率之间的连续关联通过COX模型进行建模，并表示为风险比(HR)，比较上四分位和下四分位。对于全因死亡率，NT-proBNP和GDF-15是最强的标记物，调整后的HR值分别为2.96(95%CI，2.33~3.76)和2.65(95%CI，2.17~3.24)。关于心力衰竭导致的死亡，NT-proBNP与8倍的C反应蛋白、GDF-15和胱抑素-C相关，风险增加3倍。在心脏性猝死/心律失常方面，NT-proBNP的风险增加4倍，GDF-15的风险增加一倍。生长分化因子-15与其他血管和非血管死亡的相关性最强，并可能与大出血死亡相关(HR，4.91；95%CI，1.39-17.43)。结论在急性冠脉综合征患者中，基线水平的NT-proBNP和GDF-15是与全因死亡相关的强标记物，因为它们与心力衰竭、心律失常和心性猝死有关。生长分化因子-15与其他血管或非血管原因的死亡有最强的相关性，也可能与出血死亡有关。
IMPORTANCE Mortality remains at about 5% within a year after an acute coronary syndrome event. Prior studies have assessed biomarkers in relation to all-cause or cardiovascular deaths but not across multiple causes.OBJECTIVE To assess if different biomarkers provide information about the risk for all-cause and cause-specific mortality.DESIGN, SETTING, AND PARTICIPANTS The Platelet Inhibition and Patient Outcomes (PLATO) trial randomized 18 624 patients with acute coronary syndrome to ticagrelor or clopidogrel from October 2006 through July 2008. In this secondary analysis biomarker substudy, 17 095 patients participated.MAIN OUTCOMES AND MEASURES Death due to myocardial infarction, heart failure, sudden cardiac death/arrhythmia, bleeding, procedures, other vascular causes, and nonvascular causes, as well as all-cause death.EXPOSURES At baseline, levels of cystatin-C, growth differentiation factor-15 (GDF-15), high-sensitivity C-reactive protein, high-sensitivity troponin I and T, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were determined.RESULTS The median (interquartile range) age of patients was 62.0 (54.0-71.0) years. Of 17 095 patients, 782 (4.6%) died during follow-up. The continuous associations between biomarkers and all-cause and cause-specific mortality were modeled using Cox models and presented as hazard ratio (HR) comparing the upper vs lower quartile. For all-cause mortality, NT-proBNP and GDF-15 were the strongest markers with adjusted HRs of 2.96 (95% CI, 2.33-3.76) and 2.65 (95% CI, 2.17-3.24), respectively. Concerning death due to heart failure, NT-proBNP was associated with an 8-fold and C-reactive protein, GDF-15, and cystatin-C, with a 3-fold increase in risk. Regarding sudden cardiac death/arrhythmia, NT-proBNP was associated with a 4-fold increased risk and GDF-15 with a doubling in risk. Growth differentiation factor-15 had the strongest associations with other vascular and nonvascular deaths and was possibly associated with death due to major bleeding (HR, 4.91; 95% CI, 1.39-17.43).CONCLUSIONS AND RELEVANCE In patients with acute coronary syndrome, baseline levels of NT-proBNP and GDF-15 were strong markers associated with all-cause death based on their associations with death due to heart failure as well as due to arrhythmia and sudden cardiac death. Growth differentiation factor-15 had the strongest associations with death due to other vascular or nonvascular causes and possibly with death due to bleeding.