Chantal Kopecky1, Bernd Genser2, Christiane Drechsler3, Vera Krane3, Christopher C Kaltenecker1, Markus Hengstschläger4, Winfried März5, Christoph Wanner3, Marcus D Säemann1, Thomas Weichhart6. 1. Department of Internal Medicine III, Division of Nephrology and Dialysis and. 2. BGStats Consulting, Vienna, Austria; Mannheim Institute of Public Health, Social and Preventive Medicine, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany; Institute of Public Health, Federal University of Bahia, Salvador, Brazil; 3. Department of Medicine, Division of Nephrology, University Hospital, Würzburg, Germany; 4. Institute of Medical Genetics, Medical University of Vienna, Vienna, Austria; 5. Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria; Medical Clinic V (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Mannheim Medical Faculty, Heidelberg University, Mannheim, Germany; and Synlab Academy, Synlab Laboratory Services GmbH, Mannheim, Germany. 6. Institute of Medical Genetics, Medical University of Vienna, Vienna, Austria; thomas.weichhart@meduniwien.ac.at.
Abstract
BACKGROUND AND OBJECTIVES: Impairment of HDL function has been associated with cardiovascular events in patients with kidney failure. The protein composition of HDLs is altered in these patients, presumably compromising the cardioprotective effects of HDLs. This post hoc study assessed the relation of distinct HDL-bound proteins with cardiovascular outcomes in a dialysis population. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The concentrations of HDL-associated serum amyloid A (SAA) and surfactant protein B (SP-B) were measured in 1152 patients with type 2 diabetes mellitus on hemodialysis participating in The German Diabetes Dialysis Study who were randomly assigned to double-blind treatment of 20 mg atorvastatin daily or matching placebo. The association of SAA(HDL) and SP-B(HDL) with cardiovascular outcomes was assessed in multivariate regression models adjusted for known clinical risk factors. RESULTS: High concentrations of SAA(HDL) were significantly and positively associated with the risk of cardiac events (hazard ratio per 1 SD higher, 1.09; 95% confidence interval, 1.01 to 1.19). High concentrations of SP-B(HDL) were significantly associated with all-cause mortality (hazard ratio per 1 SD higher, 1.10; 95% confidence interval, 1.02 to 1.19). Adjustment for HDL cholesterol did not affect these associations. CONCLUSIONS: In patients with diabetes on hemodialysis, SAA(HDL) and SP-B(HDL) were related to cardiac events and all-cause mortality, respectively, and they were independent of HDL cholesterol. These findings indicate that a remodeling of the HDL proteome was associated with a higher risk for cardiovascular events and mortality in patients with ESRD.
RCT Entities:
BACKGROUND AND OBJECTIVES: Impairment of HDL function has been associated with cardiovascular events in patients with kidney failure. The protein composition of HDLs is altered in these patients, presumably compromising the cardioprotective effects of HDLs. This post hoc study assessed the relation of distinct HDL-bound proteins with cardiovascular outcomes in a dialysis population. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The concentrations of HDL-associated serum amyloid A (SAA) and surfactant protein B (SP-B) were measured in 1152 patients with type 2 diabetes mellitus on hemodialysis participating in The German Diabetes Dialysis Study who were randomly assigned to double-blind treatment of 20 mg atorvastatin daily or matching placebo. The association of SAA(HDL) and SP-B(HDL) with cardiovascular outcomes was assessed in multivariate regression models adjusted for known clinical risk factors. RESULTS: High concentrations of SAA(HDL) were significantly and positively associated with the risk of cardiac events (hazard ratio per 1 SD higher, 1.09; 95% confidence interval, 1.01 to 1.19). High concentrations of SP-B(HDL) were significantly associated with all-cause mortality (hazard ratio per 1 SD higher, 1.10; 95% confidence interval, 1.02 to 1.19). Adjustment for HDL cholesterol did not affect these associations. CONCLUSIONS: In patients with diabetes on hemodialysis, SAA(HDL) and SP-B(HDL) were related to cardiac events and all-cause mortality, respectively, and they were independent of HDL cholesterol. These findings indicate that a remodeling of the HDL proteome was associated with a higher risk for cardiovascular events and mortality in patients with ESRD.
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