van der Bom J G, Bots M L, Haverkate F, Meyer P, Hofman A, Grobbee D E, Kluft C
Department of Epidemiology & Biostatistics, and The Netherlands Institute for Health Sciences, Erasmus University Medical School, Rotterdam.
Thromb Haemost. 1999 Feb;81(2):275-80.
Increased concentrations of plasminogen activator inhibitor type 1 (PAI-1) and of D-dimer have jointly been found in subjects with cardiovascular disease. To understand this apparent paradox of increased inhibition of fibrinolysis (high PAI-1) combined with increased fibrinolytic activity (high D-dimer), we examined the relation between D-dimer, PAI-1 and the activator of fibrinolysis, tissue type plasminogen activator (t-PA) in subjects with varying severity of peripheral atherosclerosis. In 325 subjects selected from the Rotterdam Study, a cohort of 7983 men and women aged 55 years and over, the ankle to brachial systolic blood pressure ratio, t-PA antigen and activity, PAI-1 antigen and D-dimer were measured. T-PA antigen and t-PA activity were, independent from each other, increased with degree of atherosclerosis; t-PA antigen increased with 3.5 ng/ml (SE 1.7, p = 0.04) and t-PA activity with 0.46 IU/ml (0.20, p = 0.02) per unit decrease in ankle to brachial pressure ratio (i.e. increase in atherosclerosis). PAI-1 antigen was not related to atherosclerosis. More marked atherosclerosis was associated with increased D-dimer, mainly in subgroups with PAI-1 antigen below 50 ng/ml, t-PA antigen below 10 ng/ml, or t-PA activity above 1.5 IU/ml. In contrast to current beliefs, we found that only a fraction of the variation of t-PA antigen was due to the variation in circulating PAI-1 antigen. A slight positive association was observed between t-PA antigen and D-dimer. PAI-1 and t-PA activity were not associated with D-dimer concentration. In conclusion, in subjects with peripheral atherosclerosis PAI-1 antigen is not increased, but low PAI-1 levels (and possibly also low levels of t-PA antigen and high levels of t-PA activity) appear to be required to increase circulating D-dimer. This suggests that increased D-dimer levels in subjects with atherosclerosis do not reflect increased inhibition, but rather reflect increased fibrinolysis.
在患有心血管疾病的受试者中，已共同发现纤溶酶原激活物抑制剂1型（PAI - 1）和D - 二聚体的浓度升高。为了理解这种纤溶抑制增加（高PAI - 1）与纤溶活性增加（高D - 二聚体）这一明显的矛盾现象，我们研究了外周动脉粥样硬化严重程度不同的受试者中D - 二聚体、PAI - 1与纤溶激活物组织型纤溶酶原激活剂（t - PA）之间的关系。在从鹿特丹研究中选取的325名受试者中（该队列包括7983名年龄在55岁及以上的男性和女性），测量了踝臂收缩压比值、t - PA抗原和活性、PAI - 1抗原以及D - 二聚体。t - PA抗原和t - PA活性彼此独立，均随动脉粥样硬化程度增加而升高；每降低一个单位的踝臂压力比值（即动脉粥样硬化程度增加），t - PA抗原升高3.5 ng/ml（标准误1.7，p = 0.04），t - PA活性升高0.46 IU/ml（0.20，p = 0.02）。PAI - 1抗原与动脉粥样硬化无关。更明显的动脉粥样硬化与D - 二聚体升高相关，主要见于PAI - 1抗原低于50 ng/ml、t - PA抗原低于10 ng/ml或t - PA活性高于1.5 IU/ml的亚组。与当前观点相反，我们发现t - PA抗原的变化只有一部分是由于循环中PAI - 1抗原的变化所致。t - PA抗原与D - 二聚体之间观察到轻微的正相关。PAI - 1和t - PA活性与D - 二聚体浓度无关。总之，在外周动脉粥样硬化患者中，PAI - 1抗原并未升高，但似乎需要低水平的PAI - 1（可能还需要低水平的t - PA抗原和高水平的t - PA活性）来增加循环中的D - 二聚体。这表明动脉粥样硬化患者中D - 二聚体水平升高并非反映纤溶抑制增加，而是反映纤溶增强。
