MacCallum P K, Cooper J A, Howarth D J, Meade T W, Miller G J
Wolfson Institute of Preventive Medicine, St. Bartholomew's and the Royal London School of Medicine and Dentistry, Queen Mary and Westfield College, UK.
Thromb Haemost. 1998 Mar;79(3):587-90.
Impaired whole blood fibrinolytic activity (FA), measured by the dilute clot lysis time (DCLT), is associated with first episodes of ischaemic heart disease (IHD) in the Northwick Park Heart Study in men, especially under 55 years, and in women. In a community-based study to investigate possible determinants of the DCLT, and therefore to assess which fibrinolytic components might be predictors of first IHD events, we measured fibrinolytic variables in a sub-sample of 150 healthy adults (73 males, 77 females) randomly selected from a single general practice. Most of the variance in DCLT (68% in men, 63% in women) was explained by tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1) activities. In multiple regression analysis there was a significant difference in the strength of the association of t-PA activity with DCLT in men compared to women (test for interaction p = 0.05), the association of t-PA activity with DCLT being significant in males but not in females. Plasma PAI-1 activity was strongly associated with DCLT in both sexes. There was no independent association of DCLT with plasma fibrinogen, t-PA antigen, other fibrinolytic inhibitors, body mass index, serum lipids or C-reactive protein. Plasma PAI-1 activity in females and both t-PA and PAI-1 activities in males are the main determinants of whole blood FA measured by DCLT. It is therefore likely that these modulators of the plasma fibrinolytic system are associated with the onset of first clinical episodes of IHD. Elevated levels of t-PA antigen were positively associated with DCLT after adjustment for age and sex and therefore indicate impaired rather than enhanced FA. Further studies of the association of FA with risk of IHD should include not only "global" measures but also assessment of t-PA and PAI-1 activities, particularly as our results suggest that their associations with IHD may differ in men and women.
在诺斯威克公园心脏研究中，通过稀释血块溶解时间（DCLT）测量的全血纤维蛋白溶解活性（FA）受损与男性尤其是55岁以下男性以及女性的缺血性心脏病（IHD）首发事件相关。在一项基于社区的研究中，为了调查DCLT的可能决定因素，从而评估哪些纤维蛋白溶解成分可能是首次IHD事件的预测指标，我们在从一个普通诊所随机选取的150名健康成年人（73名男性，77名女性）的子样本中测量了纤维蛋白溶解变量。DCLT的大部分变异（男性为68%，女性为63%）可由组织型纤溶酶原激活物（t-PA）和纤溶酶原激活物抑制剂-1（PAI-1）活性解释。在多元回归分析中，男性与女性相比，t-PA活性与DCLT的关联强度存在显著差异（交互作用检验p = 0.05），t-PA活性与DCLT的关联在男性中显著，但在女性中不显著。血浆PAI-1活性在两性中均与DCLT密切相关。DCLT与血浆纤维蛋白原、t-PA抗原、其他纤维蛋白溶解抑制剂、体重指数、血脂或C反应蛋白无独立关联。女性的血浆PAI-1活性以及男性的t-PA和PAI-1活性是通过DCLT测量的全血FA的主要决定因素。因此，血浆纤维蛋白溶解系统的这些调节因子可能与IHD首次临床发作的发生有关。调整年龄和性别后，t-PA抗原水平升高与DCLT呈正相关，因此表明FA受损而非增强。进一步研究FA与IHD风险的关联不仅应包括“整体”测量，还应评估t-PA和PAI-1活性，特别是因为我们的结果表明它们与IHD的关联在男性和女性中可能不同。
