Elsevier

Atherosclerosis

Volume 205, Issue 2, August 2009, Pages 538-543
Atherosclerosis

Inverse association of erythrocyte n-3 fatty acid levels with inflammatory biomarkers in patients with stable coronary artery disease: The Heart and Soul Study

https://doi.org/10.1016/j.atherosclerosis.2008.12.013Get rights and content

Abstract

Objective

Dietary intake of polyunsaturated n-3 fatty acids has been associated with a reduced incidence of adverse cardiovascular events. The protective mechanisms involved are not fully understood, but may include anti-inflammatory factors. We sought to investigate the relationship between n-3 fatty acid levels in erythrocyte membranes and markers of systemic inflammation in 992 individuals with stable coronary artery disease.

Methods

Cross-sectional associations of C-reactive protein (CRP) and Interleukin-6 (Il-6) with docosahexaenoic acid (DHA) and eicosapentaenoic acid (EHA) were evaluated in multivariable linear regression models adjusted for demographics, cardiovascular risk factors, medication use, exercise capacity, body-mass index, and waist-to-hip ratio.

Results

After multivariable adjustment, n-3 fatty acid levels (DHA + EPA) were inversely associated with CRP and IL-6. The inverse association of n-3 fatty acids with CRP and IL-6 was not modified by demographics, body-mass index, smoking, LDL-cholesterol, or statin use (p values for interaction > 0.1).

Conclusions

In patients with stable coronary artery disease, an independent and inverse association exists between n-3 fatty acid levels and inflammatory biomarkers. These findings suggest that inhibition of systemic inflammation may be a mechanism by which n-3 fatty acids prevent recurrent cardiovascular events.

Introduction

Epidemiologic studies have demonstrated a protective effect of dietary n-3 fatty acids on adverse cardiovascular events, particularly sudden cardiac death [1], [2], [3], [4]. The mechanisms underlying this protective effect are not well understood, and may include anti-inflammatory factors [5]. Systemic inflammation is a key component in the development and progression of atherosclerosis, and the circulating inflammatory biomarkers C-reactive protein (CRP) and interleukin-6 (IL-6) are independent risk factors for cardiovascular disease [6], [7]. The n-3 fatty acids exhibit anti-inflammatory properties which have proven useful in the treatment of systemic inflammatory diseases such as rheumatoid arthritis and Crohn's disease [8].The relationship between blood levels of n-3 fatty acids and inflammatory biomarkers in persons with stable coronary artery disease has not previously been reported. The primary aim of this study was to examine the relationship between blood levels of two n-3 fatty acids (docosahexaenoic acid, eicosapentaenoic acid)1 and two inflammatory biomarkers (CRP, IL-6). A secondary aim was to determine whether the relationship between n-3 fatty acids and inflammatory biomarkers was modified by demographics, body-mass index, smoking, LDL-cholesterol, or statin use.

Section snippets

Participants

The Heart and Soul Study is a prospective cohort study investigating the influence of psychosocial factors on cardiovascular events in outpatients with stable coronary artery disease. The enrollment process for the Heart and Soul Study has been previously described [9]. Eligible participants were recruited from outpatient clinics in the San Francisco Bay Area if they met at least one of the following inclusion criteria: (1) history of myocardial infarction, (2) angiographic evidence of at least

Results

The mean erythrocyte (DHA + EPA) level for the entire cohort was 4.2% with a standard deviation of 2.0%. The baseline characteristics of the study population categorized by tertiles of n-3 fatty acid levels are shown in Table 1. Lower levels of n-3 fatty acids were significantly associated with younger age, non-white ancestry, low income, hypertension, prior myocardial infarction, diabetes, current smoking, higher body-mass index, higher waist-to-hip ratio, lower exercise capacity, higher

Discussion

In a large cross-sectional study of patients with stable coronary artery disease, we found that blood levels of n-3 fatty acids were inversely associated with biomarkers of systemic inflammation. This inverse association persisted after multivariate adjustment for potential confounding variables, and did not appear to be modified by demographics or statin use. These findings raise the possibility that reduced inflammation may be a mechanism through which n-3 fatty acids benefit patients with

Acknowledgements

Funding sources: The Heart and Soul Study was supported by the Department of Veterans Affairs (Epidemiology Merit Review Program), the National Heart, Lung and Blood Institute (R01 HL079235), the Robert Wood Johnson Foundation (Generalist Physician Faculty Scholars Program), the American Federation for Aging Research (Paul Beeson Faculty Scholars in Aging Research Program), the Ischemia Research and Education Foundation, and the Nancy Kirwan Heart Research Fund. Ramin Farzaneh-Far, MD is

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