Revista Española de Cardiología (English Edition) Revista Española de Cardiología (English Edition)
Rev Esp Cardiol. 2019;72:407-15 - Vol. 72 Num.05 DOI: 10.1016/j.rec.2018.04.006

A Global Assessment of Circulating Prolysyl Oxidase in Nonischemic Patients With Garden-variety Heart Failure With Preserved Ejection Fraction

Benjamín Muñoz Calvo a,, Ana Villa Martínez a, Susana López Orgil b, Natalia López Andrés c, Feliciano Román García a, Virginia Víctor Palomares a, Esther de la Calle de la Villa a, Verónica Nadador Patiño a, Ignacio Arribas-Gómez b

a Unidad de Manejo Integral del Paciente con Insuficiencia Cardiaca, Servicio de Medicina Interna, Hospital Universitario Príncipe de Asturias, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain
b Fundación de Investigaciones Biomédicas, Hospital Universitario Príncipe de Asturias, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain
c Investigación Cardiovascular Traslacional, Navarra Biomed, Fundación Miguel Servet, Pamplona, Navarra, Spain

Keywords

Lysyl oxidase. Galectin-3. B-type natriuretic peptide. Heart failure with preserved ejection fraction.

Abstract

Introduction and objectives

Lysyl oxidase is overexpressed in the myocardium of patients with hypertensive cardiomyopathy. We aimed to explore whether patients with hypertensive-metabolic heart failure with preserved ejection fraction (HM-HFpEF) also have increased concentrations of circulating prolysyl oxidase (cpLOX) and its possible consequences.

Methods

We quantified cpLOX concentrations in 85 nonischemic patients with stage C, HM-HFpEF, and compared them with those of 51 healthy controls. We also assessed the correlations of cpLOX with myocardial stiffness parameters, collagen turnover products and fibrogenic cytokines, as well as the predictive value of plasma proenzyme levels at 1-year of follow-up.

Results

We detected raised cpLOX values and found that they correlated with calculated E/E’ ratios and stiffness constants. The subgroup of patients with type I diastolic dysfunction showed a single negative correlation between cpLOX and B-type natriuretic peptide whereas patients with a restrictive diastolic pattern showed a strong correlation between cpLOX and galectin-3. Kaplan-Meier analysis revealed that cpLOX > 52.20 ng/mL slightly increased the risk of a fatal outcome (log-rank = 4.45; P = .034). When Cox regression was used, cpLOX was found to be a significant independent predictor of cardiovascular death or hospitalization due to the decompensation of HM-HFpEF (HR, 1.360; 95%CI, 1.126-1.638; P = .046).

Conclusions

Patients with symptomatic HM-HFpEF show high cpLOX serum levels associated with restrictive diastolic filling indices. These levels represent a moderate risk factor for poor clinical outcome. Throughout the natural history of HM-HFpEF, we observed that cpLOX concentrations were initially negatively correlated with B-type natriuretic peptide but positively correlated with galectin-3 as advanced diastolic dysfunction developed.

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1885-5857/© 2019 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved

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