Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/40574
Title: The PCSK9-LDL Receptor Axis and Outcomes in Heart Failure: BIOSTAT-CHF Subanalysis.
Authors: Bayes-Genis, Antoni
Núñez, Julio
Zannad, Faiez
Ferreira, João Pedro
Anker, Stefan D.
Cleland, John G.
Dickstein, Kenneth
Filippatos, Gerasimos
Lang, Chim C.
Ng, Leong L.
Ponikowski, Piotr
Samani, Nilesh J.
van Veldhuisen, Dirk J.
Zwinderman, Aeilko H.
Metra, Marco
Lupón, Josep
Voors, Adriaan A.
First Published: 16-Oct-2017
Publisher: Elsevier for American College of Cardiology
Citation: Journal of the American College of Cardiology, 2017, 70 (17), pp. 2128-2136
Abstract: BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds low-density lipoprotein receptor (LDLR), preventing its recycling. PCSK9 is a risk predictor and a biotarget in atherosclerosis progression. OBJECTIVES: The aim of this study was to determine whether the PCSK9-LDLR axis could predict risk in patients with heart failure (HF). METHODS: The BIOSTAT-CHF (Biology Study to Tailored Treatment in Chronic Heart Failure) is a multicenter, multinational, prospective, observational study that included patients with worsening HF signs and/or symptoms. The primary endpoints were all-cause mortality and the composite of mortality or unscheduled hospitalizations for HF. We implemented Cox proportional hazard regression to determine the simultaneously adjusted effect of PCSK9 and LDLR on both outcomes when added to the previously validated BIOSTAT-CHF risk scores. RESULTS: This study included 2,174 patients (mean age: 68 ± 12 years; 53.2% had a history of ischemic heart disease). Median (interquartile range) PCSK9 and LDLR levels were 1.81 U/ml (1.45 to 2.18) and 2.98 U/ml (2.45 to 3.53), respectively. During follow-up, 569 deaths (26.2%) and 896 (41.2%) composite endpoints were ascertained. A multivariable analysis, which included BIOSTAT-CHF risk scores, LDLR, and statin treatment as covariates, revealed a positive linear association between PCSK9 levels and the risk of mortality (hazard ratio [HR]: 1.24; 95% confidence interval [CI]: 1.04 to 1.49; p = 0.020) and the composite endpoint (HR: 1.21; 95% CI: 1.05 to 1.40; p = 0.010). A similar analysis for LDLR revealed a negative association with mortality (HR: 0.86; 95% CI: 0.76 to 0.98; p = 0.025) and the composite endpoint (HR: 0.92; 95% CI: 0.83 to 1.01; p = 0.087). Including PCSK9 and LDLR improved risk score performance. CONCLUSIONS: The PCSK9-LDLR axis was associated with outcomes in patients with HF. Future studies must assess whether PCSK9 inhibition will result in better outcomes in HF.
DOI Link: 10.1016/j.jacc.2017.08.057
ISSN: 0735-1097
eISSN: 1558-3597
Links: http://www.sciencedirect.com/science/article/pii/S0735109717393981?via%3Dihub
http://hdl.handle.net/2381/40574
Embargo on file until: 16-Oct-2018
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2017, Elsevier for American College of Cardiology. Deposited with reference to the publisher’s open access archiving policy.
Description: The file associated with this record is under embargo until 12 months after publication, in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above.
Appears in Collections:Published Articles, Dept. of Cardiovascular Sciences

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