Aspirin resistance detected with aggregometry cannot be explained by cyclooxygenase activity: involvement of other signaling pathway(s) in cardiovascular events of aspirin-treated patients
Aspirin resistance detected with aggregometry cannot be explained by cyclooxygenase activity: involvement of other signaling pathway(s) in cardiovascular events of aspirin-treated patients
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DOI：
10.1111/j.1538-7836.2006.01958.x
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发表时间：
2006-06-01
影响因子：
10.4
通讯作者：
Sakata, Y.
中科院分区：
文献类型：
--
作者：
Ohmori, T.;Yatomi, Y.;Sakata, Y.
目的：虽然阿司匹林抵抗的概念在医学文献中被广泛报道，但其确切的机制和临床结果在很大程度上是未知的。在这项研究中，我们研究了阿司匹林治疗患者的个体血栓素生物合成和血小板聚集，以及血小板聚集试验的结果是否影响临床结果。结果如下：通过测量胶原诱导的血栓素B-2的产生，评价服用81 mg阿司匹林（n = 50）和对照组（n = 38）的受试者的血小板聚集和血小板环氧化酶-1（考克斯-1）活性。对于聚集测定法，采用光透射（LT）和激光散射法定量评价聚集体的大小和数量。阿司匹林治疗导致胶原诱导的血小板聚集的抑制，特别是从小血小板聚集体向大血小板聚集体的转变。尽管所有患者的血小板考克斯-1活性似乎均受到抑制，但血小板聚集研究显示个体间差异很大;血小板考克斯-1活性的变化仅占个体聚集的6-20%。因子分析显示，存在一个共同的因素（血小板考克斯-1以外），解释48.4%的胶原蛋白，二磷酸腺苷（ADP），胶原蛋白相关肽诱导的血小板聚集的变化。然后，我们前瞻性地纳入了136例阿司匹林治疗的患者，我们发现，在LT的上四分位数水平，或胶原蛋白诱导的大聚集体形成，是12个月内发生心血管事件的独立危险因素[LT的危险比（HR）= 7.98，P = 0.008;对于大聚集体，HR = 7.76，P = 0.007]。另一方面，糖尿病的存在是总体结局的独立危险因素（HR 1.30-11.9，P = 0.015-0.033）。结论：阿司匹林抵抗表现为血小板考克斯-1活性未受抑制，在门诊人群中是一种罕见的疾病。影响胶原诱导的血小板聚集的其他因素可能影响阿司匹林治疗患者的早期结局。
Objectives: Although the concept of aspirin resistance is extensively reported in medical literature, its precise mechanisms and clinical outcomes are largely unknown. In this study, we examined individual thromboxane biosynthesis and platelet aggregation in aspirin-treated patients, and whether the results of a platelet aggregation test influenced clinical outcomes. Results: Subjects taking 81 mg of aspirin (n = 50) and controls (n = 38) were evaluated for platelet aggregation and platelet cyclooxygenase-1 (COX-1) activity by measuring collagen-induced thromboxane B-2 production. For aggregometry, both light transmission (LT) and laser-light scattering methods were employed to quantitatively evaluate aggregate sizes and numbers. Aspirin treatment resulted in the inhibition of collagen-induced platelet aggregation, particularly the transition from small to large platelet aggregates. Although platelet COX-1 activity seemed to be uniformly inhibited in all patients, platelet aggregation studies showed great inter-individual differences; variation in platelet COX-1 activity only accounted for 6-20% of the individual aggregations. Factor analysis revealed the existence of a common factor (other than platelet COX-1) that explained 48.4% of the variations in platelet aggregation induced by collagen, adenosine diphosphate (ADP), and collagen-related peptide. We then prospectively enrolled 136 aspirin-treated patients in our study, and we found that being in the upper quartile level of LT, or with large aggregate formation induced by collagen, was an independent risk factor for developing cardiovascular events within 12 months [hazard ratio (HR) = 7.98, P = 0.008 for LT; HR = 7.76, P = 0.007 for large aggregates]. On the other hand, the existence of diabetes mellitus was an independent risk factor for overall outcomes (HR 1.30-11.9, P = 0.015-0.033). Conclusions: Aspirin resistance expressed as unsuppressed platelet COX-1 activity is a rare condition in an out-patient population. Other factor(s) affecting collagen-induced platelet aggregation may influence early outcomes in aspirin-treated patients.