Serebruany Victor L, Glassman Alexander H, Malinin Alex I, Sane David C, Finkel Mitchell S, Krishnan Ranga R, Atar Dan, Lekht Vladimir, O'Connor Christopher M
Sinai Center for Thrombosis Research, Johns Hopkins University, Baltimore, Maryland 21215, USA.
Blood Coagul Fibrinolysis. 2003 Sep;14(6):563-7. doi: 10.1097/00001721-200309000-00008.
Platelets play a key role in the progression of acute coronary syndromes (ACS). Clinical depression alone is also associated with enhanced platelet activation. The purpose of this study was to compare concentrations of established biomarkers of enhanced platelet/endothelial activation in clinically depressed versus non-depressed patients enrolled in recent clinical trials for ACS. Two hundred and eighty-one baseline plasma samples from patients with acute myocardial infarction (ASSENT-2; n = 41), with ACS (PRONTO; n = 126) and with clinical depression plus previous acute coronary syndrome within 6 months (SADHART; n = 64), and from normal healthy controls (n = 50) were analyzed. Blood was drawn before applying any therapeutic strategies including interventions, thrombolytics, infusions, and selective serotonin re-uptake inhibitors. Platelet factor 4, beta-thromboglobulin, platelet/endothelial cell adhesion molecule-1, P-selectin, thromboxane, prostacyclin, vascular cell adhesion molecule-1, and E-selectin were measured by enzyme-linked immunosorbent assay by a single core laboratory. Patients with ACS exhibited a higher degree of platelet activation than controls independently of the presence of depression. Plasma levels of P-selectin, thromboxane, prostacyclin, and vascular cell adhesion molecule-1 were the highest in the acute myocardial infarction group when compared with ACS despite the presence or absence of clinical depression. Surprisingly, patients with ACS and depression exhibited the highest levels of platelet factor 4, beta-thromboglobulin, and platelet/endothelial cell adhesion molecule-1 when compared with myocardial infarction or angina patients without clinical depression. E-selectin plasma level was constantly elevated compared with controls but did not differ among the groups dependent on the incidence of depression. The depressed plus ACS group had higher plasma levels of all biomarkers compared with the non-depressed patients. Retrospective analysis of the data from several clinical trials reveals that clinical depression is associated with enhanced activation of platelet/endothelial biomarkers even above the level expected in ACS. These findings may contribute to the unfavorable outcome associated with clinical depression in patients with ACS.
血小板在急性冠状动脉综合征（ACS）的进展中起关键作用。单纯临床抑郁症也与血小板活化增强有关。本研究的目的是比较在近期ACS临床试验中纳入的临床抑郁患者与非抑郁患者中，已确定的血小板/内皮活化增强生物标志物的浓度。分析了来自急性心肌梗死患者（ASSENT - 2；n = 41）、ACS患者（PRONTO；n = 126）、临床抑郁症合并6个月内既往急性冠状动脉综合征患者（SADHART；n = 64）以及正常健康对照者（n = 50）的281份基线血浆样本。在应用任何治疗策略（包括干预、溶栓、输液和选择性5-羟色胺再摄取抑制剂）之前采集血液。血小板因子4、β-血小板球蛋白、血小板/内皮细胞黏附分子-1、P-选择素、血栓素、前列环素、血管细胞黏附分子-1和E-选择素由单个核心实验室通过酶联免疫吸附测定法进行检测。ACS患者表现出比对照组更高程度的血小板活化，与是否存在抑郁症无关。与ACS患者相比，急性心肌梗死组中P-选择素、血栓素、前列环素和血管细胞黏附分子-1的血浆水平最高，无论是否存在临床抑郁症。令人惊讶的是，与没有临床抑郁症的心肌梗死或心绞痛患者相比，ACS合并抑郁症患者的血小板因子4、β-血小板球蛋白和血小板/内皮细胞黏附分子-1水平最高。与对照组相比，E-选择素血浆水平持续升高，但在不同抑郁症发生率的组间无差异。与非抑郁患者相比，抑郁症合并ACS组的所有生物标志物血浆水平更高。对多个临床试验数据的回顾性分析表明，临床抑郁症与血小板/内皮生物标志物的活化增强有关，甚至高于ACS患者预期的水平。这些发现可能有助于解释ACS患者中与临床抑郁症相关的不良结局。
