Risk Stratification by the ?EPA+DHA Level? and the ?EPA/AA Ratio?

Abstract

The identification of risks associated with sudden cardiac death requires further investigations. The question was addressed whether parameters can be established which not only describe an increased risk for an enhanced electrical instability of the heart but also of inflammatory events underlying plaque rupture. Emphasis is placed on dose-dependent effects of the long-chain omega-(omega-)3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Since free acids of EPA and DHA are required for most of their biological effects, it appears essential not only to build up stores in the body for release of these fatty acids, but also to provide a sustained uptake of EPA and DHA in the form of ethyl esters. In contrast to rapidly absorbed triacylglycerols from fish, ethyl esters are taken up more slowly within 24 h. For the administration of 1 g/day highly purified EPA+DHA ethyl esters (Omacor) to healthy volunteers, it is shown that EPA is increased from 0.6% to 1.4% within 10 days, while DHA is increased from 2.9% to 4.3%. After withdrawal, EPA and DHA approach baseline values within 10 days. A gas chromatographic procedure was established which requires only 10 microl of whole blood for the identification of more than 35 fatty acids. Evidence is summarized strengthening the concept that a low "EPA+DHA level" presents a risk for sudden cardiac death and that the administration of 840 mg/day of EPA+DHA ethyl esters raises the "EPA+DHA level" to approximately 6% that is associated with a marked protection from sudden cardiac death. For reducing pro-inflammatory eicosanoids and cytokines, a higher "EPA+DHA level" is required which can be achieved with an intake of 2-4 g/day of 84% EPA+DHA ethyl esters. For assessing influences from pro-inflammatory eicosanoids and cytokines, the EPA/arachidonic acid ratio ("EPA/AA ratio") was identified as diagnostic parameter. To assess the dietary EPA+DHA intake, fatty acids were determined in fish dishes of the cafeteria of the Philipps University Hospital Marburg, Germany. The EPA+DHA content of the popular Alaska Pollock was 125 +/- 70 mg/100 g. A once daily fish dish can thus not provide the 840 mg/day EPA+DHA administered in the GISSI Prevention Study in the form of ethyl ester which markedly reduced the risk of sudden cardiac death in postmyocardial infarction patients. Nonetheless, at least two preferably oily fish meals per week should be consumed as preventive measure by persons without coronary artery disease. With documented coronary heart disease, it was advised to consume approximately 1 g/day of EPA+DHA.

Omega-3 Fatty Acid Blood Levels

“…32 The total EPA+DHA blood levels increased from a mean of 3.6% to 5.4%, but ≈16% would have achieved an EPA+DHA blood level <4.8%. Rupp et al 32 have suggested that an EPA+DHA level >3.5% is the range in which sudden coronary death reduction can be observed and a dramatic reduction when EPA+DHA > 5% is achieved. These studies indicated that individual variability in blood levels could leave a substantial number of patients at elevated CHD risk because of failure to achieve a therapeutic blood level.…”

Polyunsaturated fatty acids in health and disease

“…109 For instance, reduction of proinflammatory eicosanoids and cytokines could be achieved with an intake of 2-4 g day -1 of 84 % EPA+DHA ethyl esters. 110 In the inCHIANTI study, 111 the intake of 7 g day -1 PUFAs led to higher plasma levels of AA and n-3 PUFA (mainly DHA) and these FA profiles were independently associated with lower levels of serum pro-inflammatory markers. Thies et al 112 reported that a dietary supplementation with moderate amounts of long-chain n-6 or n-3 PUFAs neither significantly affected inflammatory cell numbers nor neutrophil and monocyte responses.…”

Replacement of Reduced Highly Unsaturated Fatty Acids (HUFA Deficiency) in Dilative Heart Failure: Dosage of EPA/DHA and Variability of Adverse Peroxides and Aldehydes in Dietary Supplement Fish Oils

“…Fish consumption was similar to that in the GISSI-Prevenzione trial, where at the beginning 73.2% of the patients consumed fish once per week and 87.7% at the end [22]. The major endpoints of the GISSI-HF trial were not affected by the diet [23], which can partly be accounted for by the rather low EPA and DHA content of prepared fish dishes [24]. The Rotterdam Study did also not support a major role for fish intake in the prevention of heart failure [25].…”