Systemic levels of plasmin–antiplasmin complexes are correlated with the expansion rate of small abdominal aortic aneurysms

Background: The cystatine proteolytic system, the serine proteolytic system and the metallodependent proteolytic system have all been reported to be involved in the matrix degradation of the aortic wall, causing abdominal aortic aneurysm (AAA). Plasmin is a common activator of all three systems and could theoretically be involved in the pathogenesis of AAA by activating all three systems. However, plasmin is immediately inactivated by antiplasmin, forming plasmin–antiplasmin (PAP) complexes when it reaches the circulation. This study was designed to assess whether the systemic levels of PAP complex in conservatively treated patients with AAA could be related to the natural history of AAA. Methods: In 1994, 112 of 141 men with AAA (greater than 3 cm) diagnosed by population screening were interviewed, examined, and had blood samples taken and prepared for serum and ethylenediamine tetra‐acetic acid plasma by a standard method. The serum and plasma were frozen at − 21°C until analysis. Of the 112 patients, 99 were followed with annual control scans and blood pressure measurements for 1–5 (mean 2·5) years, and were referred for operation if the AAA exceeded 5 cm in diameter. Of the 99 patients, a random sample of 70 had their level of PAP complexes determined (Dade Behring, Rødovre, Denmark). Furthermore, the level of serum elastin peptides (SEPs) was determined by enzyme‐linked immunosorbent assay. Spearman's rank sum correlation test, multivariate linear regression analysis and receiver–operator characteristic (ROC) curve analysis were used for statistical analysis (SPSS 10.0; SPSS, Chicago, Illinois, USA). Results: The level of PAP complex was positively correlated with annual expansion rate ( r = 0·29, P = 0·01), but not with the initial AAA size ( r = 0·17, P = 0·16) or SEP ( r = 0·04, P = 0·77). The significant association to expansion persisted after adjustment for initial AAA size, SEP and smoking. Furthermore, the level of PAP complex was significantly predictive for AAAs expanding to operation recommendable size (area under ROC curve 65 per cent), with an optimal sensitivity and specificity of 65 and 67 per cent respectively. SEP level was also significantly predictive for AAAs expanding to operation recommendable size (area under ROC curve 56 per cent), with an optimal sensitivity and specificity of 56 and 57 per cent. Conclusion: The progression of AAA seems to be caused by a general activation of the proteolytic systems involving plasmin and not by genetic or environmental factors causing increased activation of specific proteases or decreased activity of their specific inhibitors. Furthermore, the level of PAP complex in patients with an aneurysm seems to have a better and independently predictive value of the natural history of AAA, compared with the best serological predictor known to date, the serum level of elastin peptides. © 2001 British Journal of Surgery Society Ltd