Sakkinen P A, Cushman M, Psaty B M, Rodriguez B, Boineau R, Kuller L H, Tracy R P
Department of Pathology, University of Vermont, Colchester, VT, USA.
Arterioscler Thromb Vasc Biol. 1999 Mar;19(3):499-504. doi: 10.1161/01.atv.19.3.499.
Plasmin-alpha2-antiplasmin complex (PAP) marks plasmin generation and fibrinolytic balance. We recently observed that elevated levels of PAP predict acute myocardial infarction in the elderly, yet little is known about the correlates of PAP. We measured PAP in 800 elderly subjects who were free of clinical cardiovascular disease in 2 cohort studies: the Cardiovascular Health Study and the Honolulu Heart Program. Median PAP levels did not differ between the Cardiovascular Health Study (6.05+/-1.46 nmol/L) and the Honolulu Heart Program (6.11+/-1.44 nmol/L), and correlates of PAP were similar in both cohorts. In CHS, PAP levels increased with age (r=0. 30), procoagulant factors (eg, factor VIIc, r=0.15), thrombin activity (prothrombin fragment F1+2, r=0.29), and inflammation-sensitive proteins (eg, fibrinogen, r=0.44; factor VIIIc, r=0.37). PAP was associated with increased atherosclerosis as measured by the ankle-arm index (AAI) (P for trend, </=0.001). PAP was negatively related to factors associated with the insulin resistance syndrome (IRS) (eg, fasting insulin, r=-0.26; body mass index, r=-0.26), possibly reflecting an association with plasminogen activator inhibitor-1 (r=-0.29). Although our study did not have sufficient power to detect a significant interaction, PAP and AAI appeared to be more weakly associated in subjects with more manifestations of the IRS: PAP appeared more strongly associated with AAI in the subgroup with 0 or 1 metabolic disorders (P</=0.001; slope estimate, -0.14) compared with the subgroup with 2 or more metabolic disorders (P=0.10; slope estimate, -0.08) and in those with non-insulin-dependent diabetes mellitus (P=0.46; slope estimate, -0.04). Although PAP reflects reactive fibrinolysis and is associated with subclinical atherosclerosis, this relationship may be weaker in populations with characteristics of the IRS, possibly reflecting the inhibitory effects of plasminogen activator inhibitor-1 on PAP. Decreased fibrinolysis in the presence of subclinical disease in subjects with hyperinsulinemia or glucose intolerance is consistent with the premise that depressed plasmin generation may enhance the progression of atherosclerosis in these people.
纤溶酶-α2-抗纤溶酶复合物（PAP）标志着纤溶酶的生成和纤维蛋白溶解平衡。我们最近观察到，PAP水平升高可预测老年人急性心肌梗死，但关于PAP的相关因素却知之甚少。在两项队列研究（心血管健康研究和檀香山心脏项目）中，我们测量了800名无临床心血管疾病的老年人的PAP。心血管健康研究（6.05±1.46 nmol/L）和檀香山心脏项目（6.11±1.44 nmol/L）的PAP中位数水平无差异，且两个队列中PAP的相关因素相似。在心血管健康研究中，PAP水平随年龄（r = 0.30）、促凝血因子（如因子VIIc，r = 0.15）、凝血酶活性（凝血酶原片段F1 + 2，r = 0.29）以及炎症敏感蛋白（如纤维蛋白原，r = 0.44；因子VIIIc，r = 0.37）升高。通过踝臂指数（AAI）测量，PAP与动脉粥样硬化增加相关（趋势P值，≤0.001）。PAP与胰岛素抵抗综合征（IRS）相关因素呈负相关（如空腹胰岛素，r = -0.26；体重指数，r = -0.26），这可能反映了与纤溶酶原激活物抑制剂-1的关联（r = -0.29）。尽管我们的研究没有足够的检验效能来检测显著的相互作用，但在IRS表现更多的受试者中，PAP与AAI的关联似乎较弱：与有2种或更多代谢紊乱的亚组（P = 0.10；斜率估计值，-0.08）以及非胰岛素依赖型糖尿病患者（P = 0.46；斜率估计值，-0.04）相比，PAP在有0种或1种代谢紊乱的亚组中与AAI的关联更强（P≤0.001；斜率估计值，-0.14）。尽管PAP反映反应性纤维蛋白溶解并与亚临床动脉粥样硬化相关，但在具有IRS特征的人群中这种关系可能较弱，这可能反映了纤溶酶原激活物抑制剂-1对PAP的抑制作用。高胰岛素血症或糖耐量异常患者在存在亚临床疾病时纤维蛋白溶解减少，这与纤溶酶生成受抑制可能促进这些人群动脉粥样硬化进展的前提一致。
