• Determine fatty acid-associated risk for cardiovascular events

• Screen for omega-3 fatty acid deficiency

• Monitor omega-3 fatty acid intake (diet, over-the-counter supplements, prescription medication)

Omega-3 fatty acids (FAs), also called n-3 polyunsaturated fatty acids (n-3 PUFAs), are involved in cell division and growth, digestion, coagulation, muscle function, and cellular transport. The 3 major omega-3 FAs are alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Fish oil and fatty fish such as salmon, mackerel, herring, and tuna are the primary dietary sources of EPA and DHA. ALA is found in plant-based foods such as green leafy vegetables, beans, and vegetable oils and is converted to EPA and DHA after being ingested.

Epidemiologic and clinical studies have shown that dietary deficiency of omega-3 FAs is associated with an increased risk of cardiovascular events, including sudden cardiac death (SCD).¹ Conversely, it has been shown that a diet rich in omega-3 FAs is associated with a decreased risk of cardiovascular events. A metaanalysis that included over 222,000 individuals found that 1 fish meal per week was associated with a 15% reduction in risk of death from coronary heart disease (CHD), and 5 or more fish meals per week was associated with a 40% reduction.² A randomized controlled study by Marchioli et al showed that a daily supplement of 850 mg of omega-3 FAs reduced the risk of CHD death by 25% and SCD by 45%.³ Numerous subsequent studies have confirmed the cardiovascular benefits of omega-3 FAs.^4,5 In addition, another study has shown that in older adults higher levels of circulating n-3 PUFA and DHA are associated with lower risk of atrial fibrillation.⁶

Based on these data, the American Heart Association,⁷ European Society for Cardiology,⁸ and other major health organizations have issued recommendations for increasing dietary intake of omega-3 FAs. However, ingestion of large amounts of omega-3 FAs can lead to gastrointestinal upset, worsening hyperglycemia in patients with impaired glucose tolerance and diabetes, and an increase in low-density lipoprotein cholesterol in patients with hypertriglyceridemia.¹

Arachidonic acid (AA), an n-6 PUFA (ie, omega-6 FA), is critical for cellular functions and primarily comes from dietary animal sources, ie, meat, eggs, dairy products. Omega-6 FAs are proinflammatory and prothrombotic (the opposite of omega-3). The optimal dietary ratio of omega-6 to omega-3 FAs is reported to be 1:1; however, the ratio resulting from a typical Western diet is approximately 10:1.⁹

This test provides a measurement of AA, EPA, and DHA. Various ratios are also reported: AA:EPA, omega-6:omega-3, and omega-3:total fatty acids (ie, the omega-3 index). The omega-3 index is an indicator of the amount of EPA and DHA relative to the amount of phospholipid fatty acids present in the individual’s sample.¹⁰ It can be used as an indicator of risk for SCD and non-fatal cardiovascular events and as a therapeutic target.^11-13 The index can also be used to assess patient compliance with omega-3 therapy and/or success or failure of such therapy (relative to the target index).

• Individuals who are being considered for omega-3 therapy (eg, those with hypercholesterolemia and/or hypertriglyceridemia and those at high risk of cardiovascular disease)

• Individuals being treated with omega-3 supplementation

• Liquid chromatography, tandem mass spectrometry (LC/MS/MS) measurement of AA, EPA, DHA, and total phospholipid fatty acids (PLFAs; ie, 21 highest concentration fatty acids [C14 through C24] present in plasma phospholipids).

• Calculation of ratios

–  Omega-3 index = (EPA+DHA) ÷ total PLFA

–  Omega-6/omega-3 = Sum of 6 omega-6 fatty acids ÷ sum of 4 omega-3 fatty acids

–  AA/EPA = % AA ÷ % EPA

• Analytical sensitivity:

The cardiovascular disease risk associated with various omega-3 indices are shown in the Table. The risk levels are based on quartiles of the reference population. Those in the first quartile are at high risk, those in the second and third are at moderate risk, and those in the fourth quartile are at low risk.

Consumption of foods high in omega-3 fatty acids (EPA and DHA), over-the-counter supplements containing omega-3 fatty acids, and prescription omega-3 fatty acids can increase the omega-3 index. An omega-3 index below the therapeutic target suggests either patient non-compliance or an inadequate dosage in individuals being treated with omega-3.

An arachidonic acid/EPA ratio and/or an omega-6/omega-3 ratio close to 1 suggests a good balance between the prothrombotic/proinflammatory omega-6 FAs and the more protective omega-3 FAs. High ratios suggest a need for dietary modifications (decrease in meat, eggs, dairy products and increase in fish intake) and/or omega-3 supplementation.