Research Institute of Internal Medicine, The National Hospital, University of Oslo, Norway
K. G. Jebsen Inflammatory Research Center, University of Oslo, Norway.
J Am Heart Assoc. 2018 Jan 12;7(2):e007009. doi: 10.1161/JAHA.117.007009.
Elevated levels of osteoprotegerin, a secreted tumor necrosis factor-related molecule, might be associated with adverse outcomes in patients with coronary artery disease. We measured plasma osteoprotegerin concentrations on hospital admission, at discharge, and at 1 and 6 months after discharge in a predefined subset (n=5135) of patients with acute coronary syndromes in the PLATO (Platelet Inhibition and Patient Outcomes) trial.
The associations between osteoprotegerin and the composite end point of cardiovascular death, nonprocedural spontaneous myocardial infarction or stroke, and non-coronary artery bypass grafting major bleeding during 1 year of follow-up were assessed by Cox proportional hazards models. Event rates of the composite end point per increasing quartile groups at baseline were 5.2%, 7.5%, 9.2%, and 11.9%. A 50% increase in osteoprotegerin level was associated with a hazard ratio (HR) of 1.31 (95% confidence interval [CI], 1.21-1.42) for the composite end point but was not significant in adjusted analysis (ie, clinical characteristics and levels of C-reactive protein, troponin T, NT-proBNP [N-terminal pro-B-type natriuretic peptide], and growth differentiation factor-15). The corresponding rates of non-coronary artery bypass grafting major bleeding were 2.4%, 2.2%, 3.8%, and 7.2%, with an unadjusted HR of 1.52 (95% CI, 1.36-1.69), and a fully adjusted HR of 1.26 (95% CI, 1.09-1.46). The multivariable association between the osteoprotegerin concentrations and the primary end point after 1 month resulted in an HR of 1.09 (95% CI, 0.89-1.33); for major bleeding after 1 month, the HR was 1.33 (95% CI, 0.91-1.96).
In patients with acute coronary syndrome treated with dual antiplatelet therapy, osteoprotegerin was an independent marker of major bleeding but not of ischemic cardiovascular events. Thus, high osteoprotegerin levels may be useful in increasing awareness of increased bleeding risk in patients with acute coronary syndrome receiving antithrombotic therapy.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872.
骨保护素（一种分泌的肿瘤坏死因子相关分子）水平升高可能与冠心病患者的不良预后有关。我们在 PLATO（血小板抑制和患者预后）试验中急性冠脉综合征患者的一个预先设定的亚组（n=5135）中测量了入院时、出院时以及出院后 1 个月和 6 个月时的血浆骨保护素浓度。
通过 Cox 比例风险模型评估骨保护素与 1 年随访期间心血管死亡、非经皮自发性心肌梗死或卒中以及非冠状动脉旁路移植术主要出血的复合终点之间的关系。在基线时，按四分位组递增，复合终点的事件发生率分别为 5.2%、7.5%、9.2%和 11.9%。骨保护素水平增加 50%与复合终点的危险比（HR）为 1.31（95%置信区间[CI]，1.21-1.42），但在调整分析中并不显著（即临床特征和 C 反应蛋白、肌钙蛋白 T、NT-proBNP[氨基末端 pro-B 型利钠肽]和生长分化因子-15 的水平）。非冠状动脉旁路移植术主要出血的相应发生率分别为 2.4%、2.2%、3.8%和 7.2%，未调整的 HR 为 1.52（95%CI，1.36-1.69），完全调整的 HR 为 1.26（95%CI，1.09-1.46）。骨保护素浓度与 1 个月后主要终点之间的多变量关联导致 HR 为 1.09（95%CI，0.89-1.33）；对于 1 个月后的主要出血，HR 为 1.33（95%CI，0.91-1.96）。
在接受双联抗血小板治疗的急性冠脉综合征患者中，骨保护素是主要出血的独立标志物，但不是缺血性心血管事件的标志物。因此，高骨保护素水平可能有助于提高接受抗血栓治疗的急性冠脉综合征患者出血风险增加的认识。
