The Role of Hemostatic Factors in Atherosclerosis in Patients with Chronic Renal Disease

Abstract

Introduction: Atherosclerotic cardiovascular disease remains the leading cause of increased morbidity and mortality observed in chronic kidney disease (CKD) patients. Endothelial dysfunction (ED) is thought to be a key initial event in the development of atherosclerosis. The aim of this study was to evaluate the potential role of hemostatic factors in atherosclerosis, thrombosis and cardiovascular complications in patients suffering from chronic renal disease.

Methods: The study was conducted on 50 renal patients divided into two groups of equal size. Group 1 consisted of 25 patients with end-stage renal disease (ESRD) on regular hemodialysis. Group 2 consisted of 25 chronic renal disease patients on conservative treatment. Twenty age- and sex-matched healthy subjects were included in the study to serve as a control group. Thrombomodulin (TM), von Willebrand factor (vWF), tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1) and hsCRP were assessed. High-resolution B-mode ultrasonography of both the common and internal carotid arteries to measure carotid intima media thickness (CIMT) was performed on all subjects.

Results: There were highly significant increases in hsCRP, TM, vWF, tPA and PAI-1 in both patient groups compared to the control group (P<0.01 for all except for TM between group 2 and 3 P<0.05) with significant increase in group 1 compared to group 2 (P<0.01). In addition, there was a highly significant increase in CIMT in both patient groups compared to the control group (P<0.01) with a significant increase in group 1 compared to group 2 (P<0.05). The study revealed significant positive correlation of hemostatic factors (TM, vWf, PAI-1 & t-PA) with creatinine, urea, hsCRP & CIMT.

Conclusion: CKD patients have increased risk of atherosclerosis as measured by CIMT, which is used as a surrogate marker of early atherosclerosis and has been shown to be a strong predictor of future myocardial infarction and stroke. They have high levels of TM, vWF, tPA, PAI-1 that correlate with kidney function, hsCRP and CIMT. Therefore, these abnormalities in hemostasis may account for the increased risk of atherothrombosis in these patients. The elevated hsCRP levels and their correlation to hemostatic factors and CIMT might provide an important clue to link a systemic marker of inflammation to atherosclerosis. Further research is required to better understand the procoagulant state in patients with CKD.