Lorenz Koller1, Bernhard Richter1, Max-Paul Winter1, Patrick Sulzgruber1, Christos Potolidis2, Florian Liebhart3, Deddo Mörtl4, Rudolf Berger5, Georg Goliasch1, Irene Lang1, Johann Wojta1, Martin Hülsmann1, Alexander Niessner6. 1. Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Austria. 2. Cardiovascular Center, Oberallgäu-Kempten, Kempten, Germany. 3. Department of Internal Medicine, University Hospital Tulln, Karl Landsteiner University of Health Sciences, Tulln, Austria. 4. Department of Internal Medicine III (Cardiology and Emergency Medicine), Landesklinikum St. Poelten, St. Poelten, Austria. 5. Department of Internal Medicine I, Cardiology and Nephrology, Hospital of St. John of God, Eisenstadt, Austria. 6. Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Austria. Electronic address: alexander.niessner@meduniwien.ac.at.
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.
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.
Authors: Valerie Yu; Dhruva Bhattacharya; Andrew Webster; Aditi Bauskar; Charles Flowers; Martin Heur; Shravan K Chintala; Tatsuo Itakura; Mark R Wilson; Joseph T Barr; Shinwu Jeong; Mingwu Wang; M Elizabeth Fini Journal: Ocul Surf Date: 2018-08-02 Impact factor: 5.033
Authors: Noemi Pavo; Dominika Lukovic; Katrin Zlabinger; David Lorant; Georg Goliasch; Johannes Winkler; Dietmar Pils; Katharina Auer; Hendrik Jan Ankersmit; Zoltán Giricz; Márta Sárközy; András Jakab; Rita Garamvölgyi; Maximilian Y Emmert; Simon P Hoerstrup; Derek J Hausenloy; Péter Ferdinandy; Gerald Maurer; Mariann Gyöngyösi Journal: Oncotarget Date: 2017-06-12