Circulatory endostatin level and risk of cardiovascular events in patients with end-stage renal disease on hemodialysis

Abstract

Background: Endostatin is released during extracellular matrix remodeling and is involved in the development of vascular pathology and cardiovascular (CV) disease. However, the role of circulating endostatin as a biomarker of vascular calcification and CV events in patients undergoing hemodialysis (HD) remains unclear. Methods: A total of 372 patients undergoing HD were prospectively recruited. Plasma endostatin levels were measured at baseline, and their associations with circulating mineral bone disease (MBD) biomarkers and abdominal aortic vascular calcification scores were analyzed. The primary endpoint was defined as a composite of CV and cardiac events. Results: Plasma levels of patients in endostatin tertile 3 were significantly associated with low-density lipoprotein cholesterol levels and predialysis systolic blood pressure in multivariate analysis. However, endostatin levels did not correlate with circulating MBD biomarkers or vascular calcification scores. Patients in endostatin tertile 3 had a significantly higher cumulative event rate for the composite of CV events (p = 0.006). Endostatin tertile 3 was also associated with an increased cumulative rate of cardiac events (p = 0.04). In multivariate Cox regression analyses, endostatin tertile 3 was associated with a 4.37-fold risk for composite CV events and a 3.88-fold risk for cardiac events after adjusting for multiple variables. Conclusion: Higher circulating endostatin levels were independently associated with atherosclerotic risk factors but did not correlate with MBD markers or vascular calcification. Higher circulating endostatin levels were associated with a greater risk of composite CV events in patients undergoing HD, and endostatin is a biomarker that helps to determine the high risk of CV events.