Omega-3 PUFAs improved endothelial function and arterial stiffness with a parallel antiinflammatory effect in adults with metabolic syndrome

doi:10.1016/j.atherosclerosis.2013.10.014

Atherosclerosis

Volume 232, Issue 1, January 2014, Pages 10-16

https://doi.org/10.1016/j.atherosclerosis.2013.10.014 Get rights and content

Highlights

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Omega-3 PUFAs treatment improved endothelial function and arterial stiffness in metabolic syndrome.
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Omega-3 PUFAs increased PAI-1 levels.
•
Omega-3 PUFAs improved the metabolic profile reducing total cholesterol, LDL and triglycerides.
•
These findings provide new insights regarding the beneficial role of omega-3 PUFAs in metabolic syndrome.

Abstract

Objectives

Metabolic syndrome (MetS) is associated with adverse cardiovascular events, and impaired vascular function. In this study we evaluated the effects of omega-3 polyunsaturated fatty acids (PUFAs) supplementation on vascular function, inflammatory and fibrinolytic process in subjects with MetS.

Methods

We studied the effect of a 12 weeks oral treatment with 2 g/day of omega-3 PUFAs in 29 (15 male) subjects (mean age 44 ± 12 years) with MetS on three occasions (day0: baseline, day 28 and day 84). The study was carried out on two separate arms (PUFAs and placebo), according to a randomized, placebo-controlled, double-blind, cross-over design. The diagnosis of MetS was based on the guidelines of Adult Treatment Panel III definition. Endothelial function was evaluated by flow-mediated dilation (FMD) of the brachial artery. Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness. Serum levels of interleukin-6(IL-6) and plasminogen activator inhibitor-1(PAI-1) were measured by ELISA.

Results

Treatment with PUFAs resulted in a significant improvement from day 0 to 28 and 84 in FMD and PWV (p < 0.001 for all). Nevertheless, treatment with placebo resulted in no significant changes in FMD (p = 0.63) and PWV (p = 0.17). Moreover, PUFAs treatment, compared to placebo, decreased IL-6 levels (p = 0.03) and increased PAI-1 levels (p = 0.03). Finally, treatment with PUFAs resulted in a significant decrease in fasting triglyceride levels from day 0 to 28 and 84 (p < 0.001) and in serum total cholesterol levels (p < 0.001).

Conclusions

In subjects with MetS, treatment with omega-3 PUFAs improved endothelial function and arterial stiffness with a parallel antiinflammatory effect.

Introduction

The metabolic syndrome (MetS), a concurrence of impaired glucose and insulin metabolism, overweight and abdominal fat distribution, dyslipidemia, and hypertension, has gain awareness and interest recently, as it is directly correlated with the development and progression of atherosclerotic cardiovascular disease and with type 2 diabetes mellitus and identifies people at higher risk of cardiovascular disease than the general population [1], [2]. Importantly, the close relationship between MetS, endothelial dysfunction and impaired arterial wall properties is linked to cardiovascular risk, coronary artery disease and mortality [3], [4], [5], [6], [7].

The use of marine omega-3 polyunsaturated fatty acids (omega-3 PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) as presented either in oil fish or in concentrated pharmaceutical preparations has demonstrate substantial cardiovascular benefits [8], [9]. Current guidelines suggest omega-3 PUFAs consumption in secondary prevention of myocardial infarction and mainly in hypertriglyceridemia. We have also shown previously that supplementation of healthy smokers with 2 g daily of omega-3 PUFAs can ameliorate smoking induce impairment of arterial function [10]. The effects of omega-3 PUFAs on vascular properties and inflammatory process remain unknown. Therefore in the present study we examined the impact of omega-3 PUFAs supplementation on the endothelial function, arterial wall properties, inflammatory and fibrinolytic process in subjects with MetS.

Section snippets

Study population

Twenty-nine patients with MetS, mean aged ± SD (44 ± 12) years old, 14 females–15 males, were included in this double-blind, placebo controlled, cross-over trial. Individual characteristics of the participants are presented in Table 1. The diagnosis of metabolic syndrome was based on the guidelines of American Heart Association and the National Heart, Lung, and Blood Institute, which update the NCEP ATP III (US National Cholesterol Education Program Adult Treatment Panel III) definition in 2004

Results

The mean age of the twenty-nine participants (15 male) was 44 ± 12 years. At baseline the mean systolic blood pressure was 133 ± 23 mmHg, the mean diastolic blood pressure was 86 ± 6 mmHg and the heart rate was 75 ± 12 beats per minute. From the study population, five subjects had diabetes mellitus and ten, twelve and seven subjects had three, four and five metabolic syndrome components respectively. At baseline, the mean values of AI75, PWV, FMD and EID were 5.64 ± 7.62%, 7.62 ± 1.59 m/s,

Discussion

In the present study we found that a daily administration of omega-3 PUFAs (2 g dose, 46% EPA–38% DHA acid) resulted in an improvement in endothelial function, arterial stiffness, inflammatory and fibrinolytic status in MetS patients. Moreover, omega-3 PUFAs treatment improved the metabolic profile of these subjects by reducing total cholesterol, LDL-cholesterol and triglycerides levels. These findings introduce the hypothesis that favorable effects of omega-3 PUFAs on endothelial function and

Conclusions

Treatment with omega-3 PUFAs may favorably affect endothelial function and the elastic properties of the arterial tree in MetS subjects, with a parallel antiinflammatory effect. The effect of omega-3 PUFAs on vascular endothelium and endothelial activation provides a novel mechanism by which omega-3 PUFAs affects vascular compliance, which requires further investigation.

Conflict of interest

There are no conflicts of interest.

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^☆: Preliminary results of this study have been presented at Annual Scientific Sessions of the American College of Cardiology, April 2013, San Francisco, CA, USA.

¹: The first two authors (D.T., A.P.) equally contributed in this study.

View full text

Omega-3 PUFAs improved endothelial function and arterial stiffness with a parallel antiinflammatory effect in adults with metabolic syndrome☆

Highlights

Abstract

Objectives

Methods

Results

Conclusions

Introduction

Section snippets

Study population

Results

Discussion

Conclusions

Conflict of interest

J Am Coll Cardiol

Atherosclerosis

Atherosclerosis

Int J Cardiol

J Am Coll Cardiol

Lancet

Lancet

Atherosclerosis

Am J Cardiol

Prog Lipid Res

Atherosclerosis

Metabolic syndrome as a precursor of cardiovascular disease and type 2 diabetes mellitus

Circulation

The central arterial burden of the metabolic syndrome is similar in men and women: the SardiNIA Study

Eur Heart J

Evaluation of the cardio-ankle vascular index, a new indicator of arterial stiffness independent of blood pressure, in obesity and metabolic syndrome

Hypertens Res

Severity of coronary atherosclerosis in patients with a first acute coronary event: a diabetes paradox

Eur Heart J

Effects of GLP-1 on forearm vasodilator function and glucose disposal during hyperinsulinemia in the metabolic syndrome

Diabetes Care

The effects of n-3 long-chain polyunsaturated fatty acid supplementation on biomarkers of kidney injury in adults with diabetes: results of the GO-fish trial

Diabetes Care

Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition

Circulation