Investigation of the relation between red blood cell omega-3 fatty acids and cardiovascular risk factors in patients with non-alcoholic fatty liver disease

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) is a spectrum of conditions ranging from simple fatty liver to non-alcoholic steatohepatitis, fibrosis and cirrhosis. Up to 30% of the global adult population is affected by NAFLD and there is no licensed treatment for this condition. NAFLD has a strong link with cardiovascular disease (CVD), suggesting that NAFLD itself promotes atherogenesis. Benefits are reported for omega-3 fatty acids (mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) in diseases of the cardiovascular system and some guidelines recommend their use. No prior study has related omega-3 fatty acid status to CVD risk in NAFLD patients without intervention.

Aim: The aim of this research was to determine the relation between red blood cell omega-3 fatty acids, as a recognised marker of status of these fatty acids, and cardiovascular risk factors in patients with NAFLD.

Methods: Data and blood samples were collected from 63 patients with NAFLD who were participants in the INSYTE study. Status of omega-3 fatty acids was determined by the level of EPA, DHA, and docosapentaenoic acid (DPA) in red blood cells. Cardiovascular risk was determined using history report, anthropometric measurements, blood pressure, carotid intimamedia thickness measurements, and blood biomarkers. The latter included blood lipids and markers of insulin resistance and vascular inflammation. Data from 105 patients with NAFLD from the WELCOME cohort were used to confirm the findings.

Results: The NAFLD patients studied had elevation of a number of cardiovascular risk factors. Most had a body mass index (BMI) indicating obesity, a waist circumference indicating excess abdominal fat, and high systolic blood pressure (SBP). Many had high blood cholesterol, triglycerides and glucose and high cholesterol to high density lipoprotein (HDL)-cholesterol ratio. More than two-thirds of the NAFLD patients had moderate or severe insulin resistance, while more than one third had low grade inflammation according to C-reactive protein concentration. Moreover, more than two-thirds of the patients were being treated for diabetes, hypertension, or hyperlipidaemia. However, diastolic blood pressure was not raised and carotid intima-media thickness was almost normal. The NAFLD patients had low omega-3 status (mean = 5.5) which is indicative of medium risk of CVD. Increasing age was a determinant of increasing omega-3 fatty acid status in these patients. A higher red blood cell DHA status was associated with lower BMI and waist circumference. Higher red blood cell DPA and DHA (and in some cases EPA and omega-3 index) was associated with lower concentrations of some inflammatory markers.

Conclusions: The NAFLD patients studied here have a normal omega-3 fatty acid status, but this indicates a medium risk of CVD. Among these patients, a higher omega-3 status is associated with a better cardiovascular risk factor profile. This suggests that treating patients with NAFLD with omega-3 fatty acids might lower their cardiovascular risk.

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Identifiers

ORCID for Philip Calder: orcid.org/0000-0002-6038-710X

ORCID for Christopher Byrne: orcid.org/0000-0001-6322-7753

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