Introduction: Several trials of omega-3 fatty acids (FA) reduced cardiovascular events whereas others have not. The ORIGIN trial of subjects with glucose intolerance or diabetes showed no benefit of omega-3 FAs on cardiac events. In the Physicians Health Study, an omega-3 index > 4% reflected a 72% reduction in cardiovascular disease risk.
Objective: To determine effect of diabetes status stratified by omega-3 index of 4% on coronary plaque progression.
Methods: 285 subjects with stable coronary artery disease on statin therapy were randomized to either omega-3 FA (1.86 g of eicosapentaenoic acid and 1.5 g of docosahexaenoic acid daily) or no omega-3 FA for 30 months. Change in coronary plaque volume was assessed by coronary computed tomographic angiography and stratified by omega-3 index of 4% and diabetes status. Plasma levels of omega-3 FAs and total FAs were measured by mass spectrometry and the omega-3 index, calculated.
Results: Mean (SD) age was 62.9 (7.8) years (17% women); mean LDL-C was < 80 mg/dL. In the total group, those with an omega-3 index ≥4% had significantly less progression of fibrous plaque compared to an index <4% (median [IQR], -0.4% [-11.9, 14.6] vs 6.6% [-6.8, 25.4]; P=0.011, respectively) (Table). When stratified by diabetes status, non-diabetics with an omega-3 index <4% had significant progression of fibrous, non-calcified and calcified coronary plaque compared to no change in plaque volumes with an omega-3 index ≥4%. In contrast, diabetic subjects had no difference in plaque volume when stratified by omega-3 index.
Conclusion: In non-diabetics, an omega-3 index ≥4% provides benefit to statin therapy in preventing progression of coronary plaque compared to an omega-3 index <4% over 30-months whereas no difference was seen in diabetic subjects. These findings suggest that diabetes status modifies the beneficial effect of omega-3 FAs even when sufficient plasma levels are achieved. Future studies should examine mechanisms for this difference.