Admission Levels of DKK1 (Dickkopf-1) Are Associated With Future Cardiovascular Death in Patients With Acute Coronary Syndromes Insights From the PLATO Trial
Admission Levels of DKK1 (Dickkopf-1) Are Associated With Future Cardiovascular Death in Patients With Acute Coronary Syndromes Insights From the PLATO Trial
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DOI：
10.1161/atvbaha.118.311042
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发表时间：
2019-02-01
影响因子：
8.7
通讯作者：
Wallentin, Lars
中科院分区：
文献类型：
--
作者：
Ueland, Thor;Akerblom, Axel;Wallentin, Lars
目的：Wnt/Wingless信号拮抗剂Dkk1(Dickkopf-1)调节血小板介导的炎症，并可能导致斑块不稳定。我们假设Dkk1与心血管结果相关。方法和结果--在柏拉图试验中，我们测定了5165名急性冠脉综合征患者在随机分组前、出院时以及1个月和6个月时的血清样本中Dkk1的水平(血小板抑制与患者预后；NCT00391872)。Dkk1浓度的中位数(四分位数范围)在基线时为0.61(0.20-1.27)ng/mL，并在随访期间升高。综合终点(心血管死亡、非程序性自发性心肌梗死或卒中)的风险比(95%顺式)在随访1年期间，基线DKK1浓度每增加50%，风险比为1.06%(1.021.10)，P=0.0011，在对14个常规临床和人口学和6个生化变量进行完全调整分析中仍然显著，包括NT-ProBNP(N末端前-B型利钠肽)、hs-TnT(高敏肌钙蛋白T)和GDF-15(生长分化因子15；1.05[1.00-1.09]；P=0.028)。这种关联主要是由与心血管死亡的关联驱动的，其中随着Dkk1的四分位数增加(2.7%、3.0%、4.3%和5.0%)，事件发生率逐渐增加，并且在完全调整的分析中仍然显著且未经修正(危险比，1.10[1.04-1.17]；P=0.002)。Dkk1的变化和1个月时的水平与预后无关。观察到替卡格雷对Dkk1放电水平的调节作用，但与预后无关。结论：在接受双重抗血小板治疗的急性冠脉综合征患者中，入院时的Dkk1水平与心血管死亡、心肌梗死或中风以及单独的心血管死亡独立相关。
Objective- The Wnt/wingless signaling antagonist DKK1 (dickkopf-1) regulates platelet-mediated inflammation and may contribute to plaque destabilization. We hypothesized that DKK1 would be associated with cardiovascular outcomes. Approach and Results- We determined DKK1 levels in serum samples obtained before randomization, at discharge, and 1 and 6 months in a subset of 5165 patients with acute coronary syndromes in the PLATO trial (Platelet Inhibition and Patient Outcomes; NCT00391872). The median (interquartile range) DKK1 concentrations were 0.61 (0.20-1.27) ng/mL at baseline and increased during follow-up. The hazard ratio (95% CIs) for the composite end point (cardiovascular death, nonprocedural spontaneous myocardial infarction, or stroke) during 1 year of follow-up, per 50% increase in baseline DKK1 concentration, was 1.06 (1.02-1.10), P=0.0011, and remained significant in fully adjusted analysis with 14 conventional clinical and demographic and 6 biochemical variables, including NT-proBNP (N-terminal pro-B-type natriuretic peptide), hs-TnT (high-sensitivity troponin T), and GDF-15 (growth differentiation factor 15; 1.05 [1.00-1.09]; P=0.028). This association was mainly driven by the association with cardiovascular death, where a gradual increase in event rates was observed with increasing quartiles of DKK1 (2.7%, 3.0%, 4.3%, and 5.0%) and remained significant and unmodified in fully adjusted analysis (hazard ratio, 1.10 [1.04-1.17]; P=0.002). Change in DKK1 and levels at 1 month were unrelated to outcomes. A modifying effect of ticagrelor on DKK1 discharge levels was observed but not associated with prognosis. Conclusions- In patients with acute coronary syndromes treated with dual antiplatelet treatment, admission DKK1 levels were independently associated with a composite of cardiovascular death, myocardial infarction, or stroke and with cardiovascular death alone.