Tonkin Andrew M, Blankenberg Stefan, Kirby Adrienne, Zeller Tanja, Colquhoun David M, Funke-Kaiser Anne, Hague Wendy, Hunt David, Keech Anthony C, Nestel Paul, Stewart Ralph, Sullivan David R, Thompson Peter L, West Malcolm, White Harvey D, Simes John
Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.
University Heart Centre Hamburg, Hamburg, Germany.
Int J Cardiol. 2015 Dec 15;201:499-507. doi: 10.1016/j.ijcard.2015.07.080. Epub 2015 Aug 16.
In patients with stable coronary heart disease (CHD), we aimed to assess 1. the prognostic power of biomarkers reflecting haemodynamics, micronecrosis, inflammation, coagulation, lipids, neurohumoral activity, and renal function; 2. whether changes in concentrations of these biomarkers over 12 months affected subsequent CHD risk; and 3. whether pravastatin modified the change in biomarker concentrations and this influenced the risk of future events.
In the LIPID study, 9014 patients were randomised to pravastatin 40 mg or placebo 3-36 months after an acute coronary syndrome. Eight biomarkers were measured at baseline (n=7863) and 12 months later (n=6434).
During a median of 6.0 (IQR 5.5-6.5) years follow-up, 1100 CHD-related deaths and nonfatal myocardial infarctions occurred, 694 after biomarker measurement at 12 months. Baseline BNP, CRP, cystatin C, D-dimer, midregional pro-adrenomedullin, and sensitive troponin I predicted recurrent CHD events. In a multivariable model, sensitive troponin I, BNP, and cystatin C had the strongest associations with outcome (P<0.001 for trend). The strongest improvement in risk prediction was achieved by including sensitive troponin I (net reclassification improvement (NRI) 5.5%; P=0.003), BNP (4.3%; P=0.02), history of MI (NRI 7.0%; P<0.001). In landmark analyses, among biomarkers, changes to 12 months in sensitive troponin I (HR 1.32 (1.03-1.70) for T3/T1), BNP (HR 1.37 (1.10-1.69) for Q4/Q1) and Lp-PLA2 (HR 1.52 (1.16-1.97)) improved CHD risk prediction.
Baseline levels and changes in sensitive troponin I, and BNP may have the potential to guide the intensity of secondary prevention therapy.
在稳定型冠心病（CHD）患者中，我们旨在评估：1. 反映血流动力学、微坏死、炎症、凝血、血脂、神经体液活性及肾功能的生物标志物的预后预测能力；2. 这些生物标志物浓度在12个月内的变化是否会影响后续CHD风险；3. 普伐他汀是否改变生物标志物浓度的变化，以及这是否会影响未来事件的风险。
在脂质研究中，9014例患者在急性冠脉综合征发生后3 - 36个月被随机分为普伐他汀40mg组或安慰剂组。在基线时（n = 7863）和12个月后（n = 6434）测量了8种生物标志物。
在中位6.0（四分位间距5.5 - 6.5）年的随访期间，发生了1100例与CHD相关的死亡和非致命性心肌梗死，其中694例发生在12个月生物标志物测量之后。基线时的脑钠肽（BNP）、C反应蛋白（CRP）、胱抑素C、D - 二聚体、中段肾上腺髓质素原及敏感肌钙蛋白I可预测CHD复发事件。在多变量模型中，敏感肌钙蛋白I、BNP和胱抑素C与结局的关联最强（趋势P<0.001）。通过纳入敏感肌钙蛋白I（净重新分类改善（NRI）5.5%；P = 0.003）、BNP（4.3%；P = 0.02）、心肌梗死病史（NRI 7.0%；P<0.001），风险预测得到了最强的改善。在标志性分析中，在生物标志物中，敏感肌钙蛋白I到12个月的变化（T3/T1时风险比（HR）1.32（1.03 - 1.70））、BNP（Q4/Q1时HR 1.37（1.10 - 1.69））和脂蛋白磷脂酶A2（HR 1.52（1.16 - 1.97））改善了CHD风险预测。
敏感肌钙蛋白I和BNP的基线水平及变化可能有指导二级预防治疗强度的潜力。
