Role of High-sensitivity C-reactive Protein in Future Cardiovascular Events in Hemodialysis Patients

Abstract

Background/Aim: The pathogenesis of cardiovascular disease (CVD) in hemodialysis (HD) patients involves inflammation and oxidative stress. High-sensitivity C-reactive protein (hs-CRP) is an established inflammatory biomarker associated with CVD. Several studies have suggested that the inflammatory biomarker pentraxin-3 (PTX-3) and the oxidative stress-related biomarker soluble lectinlike low-density lipoprotein receptor-1 (sLOX-1) are novel biomarkers for CVD in non-HD populations. This study aimed to clarify the association of these established and novel biomarkers with future cardiovascular (CV) events in HD patients. Patients and Methods: This was a single-center prospective cohort study that included 255 HD patients. The primary outcome was the composite of nonfatal and fatal CV events. The event-free survival rate between the two groups according to the median plasma level of each biomarker at baseline was evaluated using the Kaplan-Meier method. The risk for CV events at elevated levels of each biomarker was estimated using Cox proportional hazard model. Results: We observed 44 CV events during the median follow-up period of 743 days. The event-free survival rate significantly differed between the two groups in hs-CRP but not in PTX-3 or sLOX-1. The unadjusted hazard ratio (HR) for CV events in patients with hs-CRP levels above the median was 2.63 [95% confidence interval (CI)=1.37-5.02]. The HR remained significant after adjusting for age, sex, history of CVD, and diabetes (HR=2.30;. Conclusion: In HD patients, hs-CRP may have a predictable role for future CV events, whereas PTX-3 and sLOX-1 do not.Patients on hemodialysis (HD) have a high risk for morbidity and mortality due to cardiovascular disease (CVD) (1). Biomarkers that may predict future cardiovascular (CV) events may allow for the early recognition of high-risk patients and increase opportunities for appropriate therapy, improving their prognosis. Inflammation and oxidative stress are involved in the pathophysiology of CVD in patients on HD (2). Thus, biomarkers that reflect inflammation and oxidative stress may serve as predictors of future CV events in patients on HD.High-sensitivity C-reactive protein (hs-CRP) is an established inflammatory biomarker, with elevated levels predicting CV events in the general population (3, 4). Although increased levels of hs-CRP are associated with allcause or CV mortality in patients on HD (5, 6), its relationship with future CV events remains unknown. Pentraxin-3 (PTX-3) is an acute phase reactant belonging to the PTX superfamily, in which CRP belongs to, but its cellular source and regulation of production are different from those of CRP (7). PTX-3 may be closely associated with 1351