To Örebro University

BACKGROUND: Cardiovascular events are the leading cause of death in end stage renal disease (ESRD), but traditional markers of dyslipidemia are not clearly associated with cardiovascular risk in this population. Proprotein Convertase Subtilsin/Kexin type 9 (PCSK-9) could be of interest as a novel cardiovascular risk marker in ESRD due to the emergence of lipid lowering therapy based on PCSK-9 inhibition. The aim of the present study was to investigate if the convertase PCSK-9 is a potential risk marker for mortality among patients starting hemodialysis treatment.

MATERIALS AND METHODS: This is a cohort study of 265 patients starting hemodialysis between 1991-2009, with three years follow-up. The association between baseline PCSK-9 levels and mortality was assessed using Cox proportional hazards- and quantile regression models, with adjustment for potential confounders.

RESULTS: PCSK-9 levels at initiation of hemodialysis were associated to mortality in multivariable adjusted analysis. PCSK-9 levels exhibited an U-shaped association to mortality. Inclusion of the quadratic term of PCSK-9 in regression modeling optimized model performance. At baseline, PCSK-9 levels had positive correlations to Davies comorbidity score, hemoglobin and C-reactive protein while negative correlations were found for high-density lipoprotein and total cholesterol. PCSK-9 levels were higher in statin users and patients with a history of cardiovascular disease.

CONCLUSIONS: This study shows, for the first time, that the level of PCSK-9 is associated with all-cause mortality in hemodialysis patients, independently of a number of potential confounders.