Clinical correlates and heritability of erythrocyte eicosapentaenoic and docosahexaenoic acid content in the Framingham Heart Study
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.
References (78)
- et al.
The omega-3 index: a new risk factor for death from coronary heart disease?
Prev Med
(2004) - et al.
Omega-3 polyunsaturated fatty acids and cardiovascular diseases
J Am Coll Cardiol
(2009) - et al.
Cardiovascular effects of marine omega-3 fatty acids
Lancet
(2010) - et al.
Effects of omega-3 fatty acids on serum markers of cardiovascular disease risk: a systematic review
Atherosclerosis
(2006) - et al.
Omega-3 fatty acids and cardiovascular disease: effects on risk factors, molecular pathways, and clinical events
J Am Coll Cardiol
(2011) - et al.
Plasma omega-3 fatty acids and incident diabetes in older adults
Am J Clin Nutr
(2011) - et al.
The development of the Mediterranean-style dietary pattern score and its application to the American diet in the Framingham Offspring Cohort
J Nutr
(2009) - et al.
The relation between dietary intake and adipose tissue composition of selected fatty acids in US women
Am J Clin Nutr
(1998) - et al.
Fatty acid composition of subcutaneous adipose tissue and diet in postmenopausal US women
Am J Clin Nutr
(1991) - et al.
Variance component methods for detecting complex trait loci
Adv Genet
(2001)