Low Liver Density Is Linked to Cardiovascular Comorbidity in COPD: An ECLIPSE Cohort Analysis

Abstract

Purpose

Fatty liver disease is associated with cardiometabolic disorders and represents a potential key comorbidity in Chronic Obstructive Pulmonary Disease (COPD). Some intermediary mechanisms of fatty liver disease (including its histological component steatosis) include tissue hypoxia, low-grade inflammation and oxidative stress that are key features of COPD. Despite these shared physiological pathways, the effect of COPD on the prevalence of hepatic steatosis, and the association between hepatic steatosis and comorbidities in this population remain unclear. Liver density measured by computed tomography (CT)-scan is a non-invasive surrogate of fat infiltration, with lower liver densities reflecting more fat infiltration and a liver density of 40 Hounsfield Units (HU) corresponding to a severe 30% fat infiltration.

Patients and Methods

We took advantage of the international cohort ECLIPSE in which non-enhanced chest CT-scans were obtained in 1554 patients with COPD and 387 healthy controls to analyse the liver density at T12-L1.

Results

The distribution of liver density was similar and the prevalence of severe steatosis (density<40 HU) was not different (4.7% vs 5.2%, p=0.7) between COPD and controls. In patients with COPD, the lowest liver density quartile was associated, after age and sex adjustment, with coronary artery disease (OR_a=1.59, 95% CI 1.12 to 2.24) and stroke (OR_a=2.20, 95% CI 1.07 to 4.50), in comparison with the highest liver density quartile.

Conclusion

The present data indicate that a low liver density emerged as a predictor of cardiovascular comorbidities in the COPD population. However, the distribution of liver density and the prevalence of severe steatosis were similar in patients with COPD and control subjects.

Keywords:

• chronic obstructive pulmonary disease
• liver density
• steatosis
• fatty liver disease
• chest CT-scan
• cardiovascular comorbidity
• ECLIPSE cohort

Acknowledgments

The authors thank Véronic Tremblay for the body composition analysis platform of the Institut Universitaire de Cardiologie et de Pneumologie de Québec for ensuring standardization of the CT image analyses. They also thank all the subjects, investigators and study site staff who participated in ECLIPSE.

Abbreviations

CAD, Coronary Disease; COPD, Chronic Obstructive Pulmonary Disease; CRP, C Reactive Protein; CT, Computed Tomography; ECLIPSE, Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints; FLD, Fatty Liver Disease; GOLD, Global Initiative in Chronic Obstructive Lung Disease; HU, Hounsfield Unit; NAFLD, Nonalcoholic Fatty Liver Disease; OR, Odds Ratio.

Ethics Approval and Informed Consent

The study is being conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines, and has been approved by the relevant ethics and review boards at the participating centres. All patients provided written informed consent. The ECLIPSE steering and scientific committees approved the protocol for this substudy.

Data Sharing Statement

The data that support the findings of this study are available from the corresponding author with the permission of the ECLIPSE Collaborative Research Group.

Author Contributions

All authors contributed toward data analysis, drafting and revising the paper, gave final approval of the version to be published and agree to be accountable for all aspects of the work. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Disclosure

MM, NA and IV have no conflicts of interest to declare. DV reports research grants from Astra Zeneca outside the submitted work. JPD reports personal fees from Abbott Laboratories, AstraZeneca, Sanofi, GSK, Torrent Pharmaceuticals Ltd., Merck and Pfizer Canada Inc., outside the submitted work. HOC reports personal fees and grants from GSK during the conduct of the original ECLIPSE study and no other conflicts during the present study. JLP reports a grant from a consortium of homecare providers (ADIR assistance, Agiradom, IPS, ISIS Medical, LINDE, LVL Medical, SOS Oxygen and Vitalaire) and CPAP companies (Bréas, Philips, Resmed and Sefam), grants from Air Liquide Foundation, Astra-Zeneca, Mutualia, Philips, RESMED, Fisher and Paykel, and personal fees from JAZZ, ITAMAR, Perimetre, Philips, Fisher and Paykel, RESMED, Astra-Zeneca, SEFAM, Agiradom, ELIA and Teva outside the submitted work. FM reports grants and personal fees from Boehringer Ingelheim and GSK, grants from Nycomed and AstraZeneca, and grants and personal fees from Novartis and Grifols outside the submitted work. All fees are pooled with other revenues of the group of pulmonologists to which FM is a member and then shared among members of the group. The authors report no other conflicts of interest in this work.