Background and aims: Higher blood levels of the omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have been associated with fewer cardiovascular events and lower mortality in prospective studies. Our aim was to determine a target level of EPA and DHA to prevent progression of coronary artery plaque.
Methods: 218 subjects with stable coronary artery disease on statins were randomized to high-dose EPA and DHA (3.36 g daily) or no omega-3 for 30 months. Coronary plaque volume was measured by coronary computed tomographic angiography. Plasma phospholipid levels of EPA, DHA and total fatty acids were measured by gas chromatography mass spectrometry. The omega-3 fatty acid index was calculated as EPA+DHA/total fatty acid.
Results: Mean (SD) age was 62.9 (7.8) years; mean (SD) LDL-C level 78.6 (27.3) mg/dL and median triglyceride level 122 mg/dL. Subjects assigned to EPA and DHA had increased plasma EPA and DHA levels variably from 1.85% to 13.02%. Plasma omega-3 fatty acid index ≥4% prevented progression of fibrous, noncalcified, calcified and total plaque in nondiabetic subjects whereas those in the lowest quartile (<3.43%) had significant progression of fibrous, calcified and total plaque. No difference was observed in diabetic subjects.
Conclusions: EPA and DHA added to statins prevented coronary plaque progression in nondiabetic subjects with mean LDL-C <80 mg/dL, when an omega-3 index ≥4% was achieved. Low omega-3 index <3.43% identified nondiabetic subjects at risk of coronary plaque progression despite statin therapy. These findings highlight the importance of measuring plasma levels of omega-3 fatty acids early and at trial conclusion. Targeting an omega-3 index ≥4% maximizes cardiovascular benefit.
Trial registration: ClinicalTrials.gov NCT01624727.
Keywords: Coronary artery plaque; Coronary computed tomographic angiography; Eicosapentaenoic acid; Omega-3 fatty acids; Statin.
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