HDL functionality and cardiovascular outcome among nondialysis chronic kidney disease patients [S]

Abstract

CVD remains the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). CKD profoundly affects HDL composition and functionality, but whether abnormal HDL independently contributes to cardiovascular events in CKD patients remains elusive. In the present study, we assessed whether compositional and functional properties of HDL predict cardiovascular outcome among 526 nondialysis CKD patients who participate in the CARE FOR HOMe study. We measured HDL cholesterol, the content of HDL-associated proinflammatory serum amyloid A (SAA), and activities of the HDL enzymes paraoxonase and lipoprotein-associated phospholipase A2 (Lp-PLA2). In addition, we assessed the antioxidative activity of apoB-depleted serum. During a mean follow-up of 5.1 ± 2.1 years, 153 patients reached the predefined primary endpoint, a composite of atherosclerotic cardiovascular events including cardiovascular mortality and death of any cause. In univariate Cox regression analyses, lower HDL-cholesterol levels, higher HDL-associated SAA content, and lower paraoxonase activity predicted cardiovascular outcome, while Lp-PLA2 activity and antioxidative capacity did not. HDL-cholesterol and HDL-paraoxonase activity lost their association with cardiovascular outcome after adjustment for traditional cardiovascular and renal risk factors, while SAA lost its association after further adjustment for C-reactive protein. In conclusion, our data suggest that neither HDL quantity nor HDL composition or function independently predict cardiovascular outcome among nondialysis CKD patients.

Longitudinal lipid trends and adverse outcomes in patients with CKD: a 13-year observational cohort study

“…The components of HDL-C are dynamic, and different subpopulations of HDL-C can be classified by size, density, electrophoretic mobility, and apo composition. Although the effect of the size of HDL-C shifting toward atherogenic small particles in patients with CKD remains controversial, this provides a possible explanation of the lack of protective effects of high HDL-C at baseline in this population (57,58). For instance, increasing evidence suggests the pathogenic importance of dysfunctional HDL-C registry-based EMRs.…”

HDL-related biomarkers are robust predictors of survival in patients with chronic liver failure

“…HDL cholesterol efflux capacity CEC was assessed using an established assay. 20,21 J774 macrophages, maintained in DMEM with 10% fetal bovine serum were plated on 48-well plates (300,000 cells/well). Cells were labeled for 24 h with 1 lCi/ml [ 3 H]-cholesterol (Perkin Elmer, Boston, MA, USA).…”

The Role and Function of HDL in Patients with Chronic Kidney Disease and the Risk of Cardiovascular Disease

“…In turn, the enrichment of HDL with APOE can interfere with HDL metabolism and initiate atherogenesis [73,118,130]. Chronic kidney disease severely alters enzyme activities involved in HDL metabolism; it affects particle maturation and remodeling, which in consequence alters HDL composition and function [132][133][134]. Compositional alterations also include, apart from the aforementioned enrichment of HDL with proinflammatory acute-phase proteins, considerable reduction of HDL-paraoxonase content and activity [78,132,135].…”

“…Chronic kidney disease severely alters enzyme activities involved in HDL metabolism; it affects particle maturation and remodeling, which in consequence alters HDL composition and function [132][133][134]. Compositional alterations also include, apart from the aforementioned enrichment of HDL with proinflammatory acute-phase proteins, considerable reduction of HDL-paraoxonase content and activity [78,132,135]. Holzer et al [121] reported lower relative levels of APOA1 and APOA2 and higher levels of SAA1, albumin, and APOC3 in hemodialysis patients in comparison to healthy controls.…”

“…Post hoc analysis of the 4D Study revealed an independent association between HDL-associated proteins, namely SAA and surfactant protein B (SP-B) and cardiac events and overall mortality [144]. Untersteller et al [132] found that higher SAA levels and lower paraoxonase activity were predictors of adverse outcome. However, following the adjustment for traditional cardiovascular and renal risk factors, only the relationship of SAA with the occurrence of the primary endpoint remained significant.…”