Elsevier

Atherosclerosis

Volume 225, Issue 2, December 2012, Pages 425-431
Atherosclerosis

Clinical correlates and heritability of erythrocyte eicosapentaenoic and docosahexaenoic acid content in the Framingham Heart Study

https://doi.org/10.1016/j.atherosclerosis.2012.05.030Get rights and content

Abstract

Objectives

Red blood cell (RBC) levels of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA, the omega-3 index, expressed as a percent of total fatty acids) are inversely related to risk for cardiovascular disease (CVD). Although several mechanisms underlying this relationship have been proposed, understanding the associations between the omega-3 index and markers of CVD in the community can shed additional light on this question. The objectives of this study were to define the relations between the omega-3 index and clinical factors and to determine the heritability of the omega-3 index.

Methods

RBC samples (n = 3196) drawn between 2005 and 2008 from participants in the Framingham Study [Examination 8 of the Offspring cohort plus Examination 3 of the Omni (minorities) cohort] were analyzed for fatty acid composition by gas chromatography.

Results

The mean (SD) omega-3 index was 5.6% (1.7%). In multivariable regression models, the factors significantly and directly associated with the omega-3 index were age, female sex, higher education, fish oil supplementation, dietary intake of EPA + DHA, aspirin use, lipid pharmacotherapy, and LDL-cholesterol. Factors inversely associated were Offspring cohort, heart rate, waist girth, triglycerides and smoking. The total explained variability in the omega-3 index for the fully adjusted model was 73%, which included major components due to heritability (24%), EPA + DHA intake (25%), and fish oil supplementation (15%).

Conclusion

The variability in the omega-3 index is determined primarily by dietary and genetic factors. An increased omega-3 index is associated with a generally cardioprotective risk factor milieu.

Highlights

► We analyzed RBC omega-3 (omega-3 index) in Framingham and correlated them with CV risk markers. ► A higher omega-3 index is associated with a generally cardioprotective risk factor milieu. ► Omega-3 intake accounted for 40% of the variability in the omega-3 index and genetic factors 24%.

Introduction

Red blood cell (RBC) levels of the long chain marine omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which together constitute the omega-3 index [1], have been reported to be inversely related to risk for sudden cardiac death [2], [3], acute coronary syndromes [4], depression [5], and total mortality [6] as summarized in recent reviews [7], [8], [9]. These may be secondary to effects of these fatty acids on heart rate [10], inflammation [11], endothelial function [12], serum lipid levels [13] and/or platelet function [14], which themselves may be mediated by changes in eicosanoid metabolism [15], membrane biophysics [16], and gene expression [17]. Although n-3 fatty acid supplementation has been successful in reducing risk for CVD events in several large randomized trials [18], more recent experience has been less uniform [19]. Indeed, the proposed anti-arrhythmic mechanism has recently been questioned [20].

An examination of the relations between RBC omega-3 content and markers of cardiovascular disease (CVD) in the community (where fish oil supplementation is uncommon) can help generate hypotheses regarding mediating mechanisms, whereas the associations of demographic and lifestyle factors with the omega-3 index can help define the clinical and behavioral variables that determine its levels. Among the latter are obviously fish intake and fish oil supplementation, but the effects of age, sex, smoking status, etc. and of genetic factors on the omega-3 index are unclear. The purpose of this study was to examine these cross-sectional relations in a well-characterized community, the Framingham Offspring cohort.

The red blood cell (RBC) membrane has been used by several investigators to quantify relatively long-term dietary exposure to trans and marine n-3 dietary fatty acids [3], [21], [22]. Indeed, fatty acid biomarkers (in plasma, plasma phospholipids, RBCs, etc) are better predictors of incident congestive heart failure [23], atrial fibrillation [24] and type 2 diabetes mellitus [25] than are questionnaire-based intake estimates. Hence n-3 fatty acid biomarkers are superior to n-3 fatty acid intake estimates for predicting disease outcomes.

Section snippets

Participants

Children (and their spouses) of the original Framingham Heart Study cohort were recruited in 1971 and constitute the Framingham Offspring Study [26]. The detailed study designs and methods have been extensively described (http://www.nhlbi.nih.gov/about/framingham). In 1994, recruitment began for the Framingham Omni cohort comprising residents aged 40–74 who described themselves as members of a minority group, [27]. The Offspring Exam 8 and Omni Exam 3 were scheduled together from 2005 to 2008,

Clinical correlates

There were several differences between the Offspring (white) and Omni (non-white) cohorts as seen in Table 1. The Offspring were on average 4 years older, less educated, and had a lower prevalence of diabetes. They also had higher levels of alcohol consumption, smoking, physical activity and fish oil supplementation. The overall mean (SD) omega-3 index was 5.62% (1.71%). It was 5.56% (1.69%) in the Offspring, but 6.16% (1.83%) in Omni (p < 0.0001) despite fewer Omni participants taking fish oil

Discussion

The purpose of this study was to explore the clinical, demographic, behavioral and genetic correlates of the omega-3 index in a well-defined cohort of subjects from the Framingham Heart Study. The cohort was comprised of 91% white participants (Offspring) and 9% minorities (Omni). The omega-3 index was lower in Offspring than Omni despite fish oil supplementation being more prevalent in the former; this effect remained after multivariable adjustment. Whether a higher dietary intake of n-3 fatty

Sources of support

This study was supported by National Heart Lung and Blood Institute (NHLBI; R01 HL089590) and by Contract N01-HC-25195, the Framingham Heart Study (NHLBI) and Boston University School of Medicine.

Potential conflicts of interest

WSH is a scientific advisor to companies with interests in fatty acids including Monsanto, Aker Biomarine, Omthera, Amarin and GlaxoSmithKline, and was a speaker for the latter. In addition, he is the owner of OmegaQuant Analytics, LLC and an employee of Health Diagnostics Laboratory, Inc., both of which offer blood fatty acid testing commercially. None of the other authors have any potential conflicts to disclose. All authors had full access to all of the data in the study and take

Roles of authors

WSH, SJR, RSV, and MGL designed research (project conception, development of overall research plan, and study oversight); WSH conducted research (oversaw the hands-on lab analyses); JVP and SML (with oversight from MGL) analyzed data or performed statistical analysis; WSH and JVP wrote paper with major editorial input from SJR, MGL and RSV; and WSH had primary for final content. All authors read and approved the final manuscript.

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