Omega-3 fatty acids and cardiovascular disease: a case for omega-3 index as a new risk factor

Abstract

The omega-3 fatty acids (FAs) found in fish and fish oils (eicosapentaenoic and docosahexaenoic acids, EPA and DHA) have been reported to have a variety of beneficial effects in cardiovascular diseases. Ecological and prospective cohort studies as well as randomized, controlled trials have supported the view that the effects of these FAs are clinically relevant. They operate via several mechanisms, all beginning with the incorporation of EPA and DHA into cell membranes. From here, these omega-3 FA alter membrane physical characteristics and the activity of membrane-bound proteins, and once released by intracellular phospholipases, can interact with ion channels, be converted into a wide variety of bioactive eicosanoids, and serve as ligands for several nuclear transcription factors thereby altering gene expression. In as much as blood levels are a strong reflection of dietary intake, it is proposed that an omega-3 FA biomarker, the omega-3 index (erythrocyte EPA+DHA) be considered at least a marker, if not a risk factor, for coronary heart disease, especially sudden cardiac death. The omega-3 index fulfils many of the requirements for a risk factor including consistent epidemiological evidence, a plausible mechanism of action, a reproducible assay, independence from classical risk factors, modifiability, and most importantly, the demonstration that raising tissue levels will reduce risk for cardiac events. For these and a number of other reasons, the omega-3 index compares very favourably with other risk factors for sudden cardiac death.

Figures

Fig. 1

Risk for MI by median omega-3 FA intake estimated from reported fish intake in the Japan Public Health Center-Based Study Cohort I. 41,578 subjects; 40-59 yrs; 10 yr f/u. Age, sex, smoking, alcohol, BMI, Hx HTN and diabetes, drug use for elevated cholesterol, educational level, sports in leisure time, and quintiles of dietary fruits, vegetables, sat fat, mono fat, n-6 fat, cholesterol and kcal. P for trend =0.02. Adapted from Iso et al. [15].

Fig. 2

The relationship between RBC EPA+DHA content and risk for primary cardiac arrest (right) or sudden cardiac death (left). The former data were derived from Siscovick et al. [33] from a population-based case control study, and the latter from Albert et al. [34] from a case-control study nested in the prospective Physicians' Health Study. The omega-3 index was estimated from the latter data set (which measured whole blood long-chain omega-3 FA content) using equations described by Harris and von Schacky [36].

Fig. 3

Proposed risk zones for the omega-3 index (RBC EPA+DHA). Proposed cutpoints were estimated from a review of the literature [36].

Fig. 4

The multivariable-adjusted relative risk for sudden cardiac death (RR SCD) by quartile of blood omega-3 FA compared to other, more traditional blood-borne risk factors. The quartiles at highest risk (black bars) are set at a relative risk of 1.0 for the presumed highest-risk levels of each marker. Each subsequent lighter bar represents the risk at each decreasing (or, for HDL and omega-3 FA, increasing) quartile. Adapted from the Physicians' Health Study, Albert et al. [34,42]. CRP=C reactive protein; Hcy=homocysteine; TC=total cholesterol; LDL=low density lipoprotein cholesterol; HDL=high density lipoprotein cholesterol; Tg=triglycerides.

Fig. 5

RBC EPA+DHA by category of reported consumption of tuna or non-fried fish per month. Groups differed by ANOVA (pet al. [45] with permission.