Clusterin/apolipoprotein J is independently associated with survival in patients with chronic heart failure

Abstract

Background: Clusterin/apolipoprotein J (CLU) is a ubiquitous expressed glycoprotein with cytoprotective properties capable to prevent myocardial injury in experimental studies. We hypothesized that decreasing levels of CLU might be involved in progression of chronic heart failure (HF) and therefore represent a potential biomarker for prognosis in this vulnerable group of patient.

Objective: We aimed to determine the prognostic value of plasma CLU in patients with HF.

Methods: Plasma CLU levels were determined in a prospectively recruited cohort comprising 318 patients with chronic HF and validated in a second cohort comprising 346 patients with advanced HF.

Results: During a median follow-up time of 3.2 years (interquartile range 2.0-4.9), 119 patients (37.3%) deceased including 83 patients (26.1%), who died from cardiovascular events. CLU was an inverse predictor of mortality with a crude hazard ratio (HR) per increase of 1 standard deviation (1 SD) of 0.75 (95% confidence interval [CI]: 0.62 to 0.9, P = .002) and specifically cardiovascular mortality with an HR per 1 SD of 0.67 (95% CI: 0.53-0.84, P < .001). CLU remained significantly associated with cardiovascular mortality after comprehensive adjustment for established HF-related risk factors and potential confounders with an adjusted HR per 1 SD of 0.79 (95% CI: 0.63-0.99, P = .042). Validation in the second cohort yielded similar results and confirmed CLU as independent prognosticator in patients with chronic HF.

Conclusion: Our results point toward an ongoing consumption of CLU involved in the complex pathophysiology of HF and suggest CLU as novel and promising biomarker for prognosis in patients with chronic HF.

Keywords: Apolipoprotein J; Biomarker; Clusterin; Heart failure; Prognosis.