Glueck Charles J, Munjal Jitender, Aregawi Dawit, Agloria Maliha, Winiarska Magdalena, Khalil Qasim, Wang Ping
Cholesterol Center, Cincinnati, Ohio 45229, USA.
Transl Res. 2007 Aug;150(2):93-100. doi: 10.1016/j.trsl.2007.03.005. Epub 2007 May 25.
Thrombophilia-hypofibrinolysis may play an important role in rare premature (< or = age 45 years) arterial occlusive events in atherothrombotic cardiovascular (ATCVD) disease, particularly in normolipidemic patients. Whether thrombophilia-hypofibrinolysis contributed to ATCVD < or = age 45 years was assessed in 78 men and 40 women with 230 ATCVD events (myocardial infarction (MI) [n = 60], coronary artery bypass graft [CABG, n = 33], angioplasty [n = 52], chronic angina [n = 41], ischemic stroke [n = 11], transient ischemic attack [TIA, n = 24], claudication [n = 9]). Cases were compared with healthy normal adult controls (44 men and 76 women). In men, the Factor V Leiden mutation was present in 6/63 (10%) cases versus 0/44 (0%) controls (P = 0.042), Factor VIII was high (>150%) in 16/60 (27%) cases versus 1/42 (2%) controls (P = 0.001), Factor XI was high (>150%) in 9/57 (16%) cases versus 0/42 (0%) controls (P = 0.009), and plasminogen activator inhibitor activity (PAI-Fx) was high (>21.1 U/mL) in 15/63 (24%) cases versus 3/43 (7%) controls (P = 0.023). In women, protein C was low (<73%) in 4/26 (15%) cases versus 0/74 (0%) controls (P = 0.004), and free protein S was low (<66%) in 5/27 (19%) cases versus 2/74 (3%) controls (P = 0.014). In women, Factor XI was high (>150%) in 3/27 (11%) cases versus 1/74 (1%) controls (P = 0.057), and the lupus anticoagulant was present in 9/32 (28%) cases versus 2/51 (4%) controls (P = 0.002). In patients with ATCVD < or = age 45 years, thrombophilias (Factor V Leiden, Factor VIII, Factor XI, protein C and S deficiency, lupus anticoagulant) and hypofibrinolysis (PAI-Fx, Lp[a]) may promote arterial thrombosis, which is synergistic with atherosclerotic endothelial injury.
血栓形成倾向-纤溶功能减退可能在动脉粥样硬化血栓形成性心血管疾病（ATCVD）中罕见的早发性（≤45岁）动脉闭塞事件中起重要作用，尤其是在血脂正常的患者中。我们评估了78名男性和40名女性（共发生230次ATCVD事件，包括心肌梗死（MI）[n = 60]、冠状动脉搭桥术（CABG，n = 33）、血管成形术[n = 52]、慢性心绞痛[n = 41]、缺血性中风[n = 11]、短暂性脑缺血发作（TIA，n = 24]、跛行[n = 9]）中，血栓形成倾向-纤溶功能减退是否导致≤45岁的ATCVD。将病例与健康正常成人对照组（44名男性和76名女性）进行比较。在男性中，6/63（10%）的病例存在凝血因子V莱顿突变，而对照组为0/44（0%）（P = 0.042）；16/60（27%）的病例凝血因子VIII水平高（>150%），而对照组为1/42（2%）（P = 0.001）；9/57（16%）的病例凝血因子XI水平高（>150%），而对照组为0/42（0%）（P = 0.009）；15/63（24%）的病例纤溶酶原激活物抑制剂活性（PAI-Fx）高（>21.1 U/mL），而对照组为3/43（7%）（P = 0.023）。在女性中，4/26（15%）的病例蛋白C水平低（<73%），而对照组为0/74（0%）（P = 0.004）；5/27（19%）的病例游离蛋白S水平低（<66%），而对照组为2/74（3%）（P = 0.014）。在女性中，3/27（11%）的病例凝血因子XI水平高（>150%），而对照组为1/74（1%）（P = 0.057）；9/32（28%）的病例存在狼疮抗凝物，而对照组为2/51（4%）（P = 0.002）。在≤45岁的ATCVD患者中，血栓形成倾向（凝血因子V莱顿、凝血因子VIII、凝血因子XI、蛋白C和S缺乏、狼疮抗凝物）和纤溶功能减退（PAI-Fx、Lp[a]）可能促进动脉血栓形成，这与动脉粥样硬化性内皮损伤具有协同作用。
