Atherosclerosis is associated with plasminogen activator inhibitor type‐1 in chronic haemodialysis patients
Authors: PENG YOUMING , LIU HONG , LIU FUYOU , OUYANG LIN , CHENG MEICHU , GAO LEI , PAN FULIN , LIU YINGHONG , CHEN XING , LI JUN 
Published: October 2008

Aim:  The aim of the present report was to investigate the probable association of circulating levels of PAI‐1 and expression of PAI‐1 in internal iliac artery walls with atherosclerotic disease in chronic haemodialysis (HD) patients.

Methods:  Sixty‐eight non‐diabetic HD patients and 50 age‐ and sex‐matched healthy normotensive controls participated in the study. Atherosclerotic disease in both groups was assessed by measuring intima‐media thickness (IMT) and plaque score of the common carotid arteries using an ultrasound scanner. Levels of serum PAI‐1, C‐reactive protein (CRP), interleukin (IL)‐6 and lipids profile were measured. Internal iliac artery samples were obtained at the time of renal transplantation. Quantitative expression of PAI‐1 in internal iliac artery walls was assessed by positive unit (pu) value using an immunohistochemical method. In addition, the IMT and carotid plaque score were analyzed in relation to circulating levels of PAI‐1 and expression of PAI‐1 in internal iliac artery walls.

Results:  Compared with control subjects, HD patients had significantly increased common carotid artery (CCA)‐IMT (P = 0.002). Atherosclerotic plaques were detected in 42 (61.76%) of HD patients and in two (4%) controls. The above ultrasonographic indices were correlated with age in HD patients (P < 0.001). A significant relationship was observed between IMT and systolic blood pressure (BP), low‐density lipoprotein in HD patients (P < 0.001 and P < 0.001, respectively). In HD patients, IMT was significantly correlated with CRP and IL‐6 (P < 0.001 and P < 0.001, respectively). In HD patients, a close correlation was found between serum PAI‐1 level, CRP and IL‐6 (P < 0.01 and P < 0.01, respectively). A close correlation was also found between PAI‐1 pu value, CRP and IL‐6 (P < 0.01 and P < 0.01 respectively). Serum PAI‐1 level is highly correlated to PAI‐1 pu value (P < 0.01). In HD patients, CCA‐IMT and plaque score were correlated significantly with circulating levels of PAI‐1(P < 0.01 and P < 0.05, respectively) and expression of PAI‐1 in internal iliac artery walls (P < 0.01 and P < 0.05, respectively). Multivariate analysis showed that log CRP values were a strong independent contributor to CCA‐IMT and plaque score (P = 0.03 and P = 0.04, respectively). Multivariate analysis showed that serum PAI‐1 concentration was a strong independent correlate of CCA‐IMT and carotid plaque score (P = 0.004 and P = 0.009, respectively). Multivariate analysis also showed that expression of PAI‐1 in internal iliac artery walls was a strong independent correlate of CCA‐IMT and carotid plaque score (P = 0.008 and P = 0.005, respectively).

Conclusion:  The circulating levels of PAI‐1 and expression of PAI‐1 in internal iliac artery walls were statistically associated with CRP, IL‐6 and low‐density lipoprotein cholesterol. Moreover, in HD patients, CCA‐IMT and plaque score were correlated significantly with circulating levels of PAI‐1 and expression of PAI‐1 in internal iliac artery walls and the circulating levels of PAI‐1 and expression of PAI‐1 in internal iliac artery walls were independent predictors of carotid atherosclerosis including CCA‐IMT and carotid plaque score. The correlations may suggest that increased circulating PAI‐1 level and upregulated expression of PAI‐1 in the vasculature could indicate a chronic endothelium activated state and PAI‐1 may more precisely identify the risk of atherothrombosis and be useful as a target for anti‐inflammatory treatment strategies.