Brigham and Women's Hospital, Boston, Massachusetts, USA.
J Am Coll Cardiol. 2012 Jul 24;60(4):332-8. doi: 10.1016/j.jacc.2012.04.023.
This study sought to investigate whether pregnancy-associated plasma protein-A (PAPP-A) is useful for risk assessment in non-ST-segment elevation acute coronary syndrome (NSTE-ACS).
PAPP-A is a high molecular weight, zinc-binding metalloproteinase that is associated with vulnerable plaque and may be a predictor of cardiovascular disease and mortality.
We measured PAPP-A at baseline in 3,782 patients with non NSTE-ACS randomized to ranolazine or placebo in the MERLIN-TIMI 36 (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST Elevation Acute Coronary Syndromes) trial and followed for an average of 1 year. A cut point of 6.0 μIU/ml was chosen from pilot work in this cohort.
PAPP-A >6.0 μIU/ml at presentation was associated with higher rates of cardiovascular death (CVD) or myocardial infarction (MI) at 30 days (7.4% vs. 3.7%, hazard ratio [HR]: 2.01; 95% confidence interval [CI]: 1.43 to 2.82; p < 0.001) and at 1 year (14.9% vs. 9.7%, HR: 1.63; 95% CI: 1.29 to 2.05; p < 0.001). PAPP-A was also associated with higher rates of CVD (HR: 1.94; 95% CI: 1.07 to 3.52, p = 0.027) and myocardial infarction (HR: 1.82; 95% CI: 1.22 to 2.71, p = 0.003) individually at 30 days. There was no difference in the risk associated with PAPP-A stratified by baseline cardiac troponin I [Accu-TnI >0.04 μg/l], p interaction = 0.87). After adjustment for cardiac troponin I, ST-segment deviation, age, sex, diabetes, smoking, hypertension, and coronary artery disease, PAPP-A was independently associated with CVD/myocardial infarction at 30 days (adjusted HR: 1.62, 95% CI: 1.15 to 2.29; p = 0.006) and 1 year (adjusted HR: 1.35, 95% CI: 1.07 to 1.71; p = 0.012). PAPP-A also improved the net reclassification for CVD/MI (p = 0.003). There was no significant interaction with ranolazine.
PAPP-A was independently associated with recurrent cardiovascular events in patients with NSTE-ACS. This finding supports PAPP-A as a candidate prognostic marker in patients with ACS and supports investigation of its therapeutic implications.
本研究旨在探讨妊娠相关血浆蛋白 A（PAPP-A）在非 ST 段抬高型急性冠状动脉综合征（NSTE-ACS）中的风险评估是否有用。
PAPP-A 是一种高分子量、锌结合金属蛋白酶，与易损斑块有关，可能是心血管疾病和死亡率的预测因子。
我们在 MERLIN-TIMI 36（非 ST 段抬高型急性冠状动脉综合征中瑞那唑胺对减少缺血的代谢效率）试验中测量了 3782 名非 NSTE-ACS 患者的基线 PAPP-A，并随机分配给雷诺嗪或安慰剂，平均随访 1 年。从该队列的初步研究中选择了 6.0 μIU/ml 的切点。
发病时 PAPP-A＞6.0 μIU/ml 与 30 天心血管死亡（CVD）或心肌梗死（MI）的发生率较高相关（7.4% vs. 3.7%，风险比[HR]：2.01；95%置信区间[CI]：1.43 至 2.82；p＜0.001）和 1 年（14.9% vs. 9.7%，HR：1.63；95%CI：1.29 至 2.05；p＜0.001）。PAPP-A 还与 30 天 CVD（HR：1.94；95%CI：1.07 至 3.52，p=0.027）和心肌梗死（HR：1.82；95%CI：1.22 至 2.71，p=0.003）的风险增加独立相关。根据基线心脏肌钙蛋白 I[Accu-TnI＞0.04μg/l]分层，PAPP-A 与风险之间无差异[p 交互=0.87]。在校正心脏肌钙蛋白 I、ST 段偏移、年龄、性别、糖尿病、吸烟、高血压和冠状动脉疾病后，PAPP-A 与 30 天 CVD/心肌梗死（校正 HR：1.62，95%CI：1.15 至 2.29；p=0.006）和 1 年（校正 HR：1.35，95%CI：1.07 至 1.71；p=0.012）独立相关。PAPP-A 还改善了 CVD/MI 的净重新分类（p=0.003）。与雷诺嗪无显著交互作用。
PAPP-A 与 NSTE-ACS 患者的复发性心血管事件独立相关。这一发现支持 PAPP-A 作为 ACS 患者的候选预后标志物，并支持对其治疗意义的研究。
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