Author, as appears in the article.: Girona J; Ibarretxe D; Plana N; Guaita-Esteruelas S; Amigo N; Heras M; Masana L
Department: Medicina i Cirurgia Ciències Mèdiques Bàsiques
URV's Author/s: Girona Tell, Josefa / GUAITA ESTERUELAS, SANDRA / HERAS IBAÑEZ, MERCEDES / Ibarretxe Gerediaga, Daiana / Masana Marín, Luis / Plana Gil, Núria
Keywords: Rs11591147 Pcsk9 Mutations Metabolic syndrome Lipids Ldl-cholesterol Inhibition High-risk Expression Ester transfer protein Density-lipoprotein cholesterol Coronary-heart-disease Cetp Autosomal-dominant hypercholesterolemia Anacetrapib
Abstract: © 2016 The Author(s). Background: PCSK9 inhibition is a new powerful cholesterol-lowering strategy. Recently, it was reported that CETP inhibitors influence PCSK9 levels as an off-target effect. We explored the relationship between circulating PCSK9 levels and CETP activity in patients with metabolic disease who were not on lipid-lowering therapy. Methods: Plasma CETP activity and PCSK9 levels were measured in 450 participants (median age, 58 years; 49 % women) who attended the metabolism unit because of metabolic syndrome (MetS) (78 %), atherogenic dyslipidemia (32 %), obesity (50 %), type 2 diabetes mellitus (72 %), and other risk factors (13 %). A 6 week lipid-lowering drug wash-out period was established in treated patients. Results: Both PCSK9 levels and CETP activity were higher in patients with an increasing number of MetS components. PCSK9 levels were positively correlated with CETP activity in the entire cohort (r = 0.256, P < 0.0001) independent of age, gender, body mass index (BMI), systolic blood pressure (SBP), LDL cholesterol (LDL-C), triglycerides and glucose. Individuals with the loss-of-function PCSK9 genetic variant rs11591147 (R46L) had lower levels of PCSK9 (36.5 %, P < 0.0001) and LDL-C (17.8 %, P = 0.010) as well as lower CETP activity (10.31 %, P = 0.009). This association remained significant in the multiple regression analysis even after adjusting for gender, age, BMI, LDL-C, triglycerides, glucose, lecithin-cholesterol acyltransferase, SBP and MetS (P = 0.003). Conclusions: Our data suggest a metabolic association between PCSK9 and CETP independent of lipid-lowering treatment. The clinical implications of this metabolic relationship could be relevant for explaining the effect of PCSK9 and CETP inhibition on overall lipid profiles.
Thematic Areas: Saúde coletiva Medicina ii Medicina i Internal medicine Interdisciplinar Farmacia Endocrinology, diabetes and metabolism Endocrinology & metabolism Educação física Ciências biológicas ii Ciências biológicas i Cardiology and cardiovascular medicine Cardiac & cardiovascular systems Biotecnología
licence for use: https://creativecommons.org/licenses/by/3.0/es/
ISSN: 14752840
Author's mail: daiana.ibarretxe@urv.cat josefa.girona@urv.cat josefa.girona@urv.cat luis.masana@urv.cat
Author identifier: 0000-0002-6267-8779 0000-0002-6267-8779 0000-0002-0789-4954
Record's date: 2024-09-07
Papper version: info:eu-repo/semantics/publishedVersion
Link to the original source: https://cardiab.biomedcentral.com/articles/10.1186/s12933-016-0428-z
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: Cardiovascular Diabetology. 15 (1): 107-
APA: Girona J; Ibarretxe D; Plana N; Guaita-Esteruelas S; Amigo N; Heras M; Masana L (2016). Circulating PCSK9 levels and CETP plasma activity are independently associated in patients with metabolic diseases. Cardiovascular Diabetology, 15(1), 107-. DOI: 10.1186/s12933-016-0428-z
Article's DOI: 10.1186/s12933-016-0428-z
Entity: Universitat Rovira i Virgili
Journal publication year: 2016
Publication Type: Journal Publications
Repositori URV