Abstract
Background: In REDUCE-IT, high-dose eicosapentaenoic acid (EPA) was beneficial in high-risk patients without clinical CVD independent of triglyceride levels. Whether the benefit of higher plasma EPA extends to those without subclinical CVD is unclear. Hypothesis: In those without clinical CVD, plasma omega-3 fatty acid (O3FA) levels predict long-term CVD events, and subclinical CVD measured by coronary artery calcium (CAC) modifies the effect such that individuals with the highest CAC attain the greatest benefit from higher O3FA. Methods: We examined 6568 MESA participants with plasma EPA and docosahexaenoic acid (DHA) levels measured at baseline and classified them by tertiles of EPA and DHA and by CAC category (0, 1-99, ≥100). Our outcome was time to CVD event (myocardial infarction, angina, cardiac arrest, stroke, CVD death). Cox regression models were used to assess the associations between log-transformed EPA and DHA and CVD events adjusted for demographic factors, CVD risk factors, and medication use. Results: Mean age was 62.1±10.2 and 52.9% were females. Higher log(EPA) (adjusted hazard ratio, aHR = 0.83; 95% CI, 0.74-0.93; P = 0.002) and log(DHA) (aHR = 0.80; 95% CI, 0.66-0.96; P = 0.019) were independently associated with fewer CVD events. The difference in absolute CVD event rates between the lowest and highest EPA tertile increased at higher CAC levels (Figure). The adjusted HR for highest compared to lowest EPA tertile within CAC 0 was 1.02 (95% CI, 0.72-1.45), CAC 1-99 was 0.71 (95% CI, 0.51-0.98), and CAC≥100 was 0.66 (95% CI, 0.52-0.83). A similar association was seen in tertiles of DHA by CAC category. These findings were consistent by sex and race category and after adjusting for O3FA supplement use. Conclusion: In an ethnically diverse population free of clinical CVD at baseline, higher plasma O3FA levels were associated with fewer CVD events. The absolute reduction in CVD events with higher O3FA levels was more apparent at higher CAC scores.
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