Plasma n-3 and n-6 Fatty Acids Are Differentially Related to Carotid Plaque and Its Progression: The Multi-Ethnic Study of Atherosclerosis

Objective -3 (n-3) fatty acids (FAs) have long been considered healthful dietary components, yet recent clinical trials have questioned their cardiovascular benefits. By contrast, the -6 (n-6) FAs have been considered harmful, proatherogenic macronutrients, despite an absence of empirical evidence supporting this hypothesis. We aimed to determine whether plasma n-3 and n-6 FAs are related to risk of carotid plaque and its progression in 3327 participants of MESA (Multi-Ethnic Study of Atherosclerosis). Approach and Results Carotid plaque was assessed using ultrasonography at baseline and after a median period of 9.5 years. Plasma phospholipid n-3 and n-6 FAs were determined using gas chromatography-flame ionization detection. Relative risk regression analyses assessed the relations of FAs with the presence or progression of carotid plaque adjusted for typical cardiovascular disease risk factors. At baseline, it was found that participants in the fourth quartile of n-3 docosahexaenoic acid showed a 9% lower risk of carotid plaque (P=0.05), whereas those in the second quartile of n-3 -linolenic acid showed an 11% greater risk compared with respective referent quartiles (P=0.02). In prospective analyses, individuals in the top quartile of docosahexaenoic acid showed a 12% lower risk of carotid plaque progression during 9.5 years compared with those in the referent quartile (P=0.002). No significant relations were observed among n-6 FAs and plaque outcomes. No significant race/ethnicity interactions were found. Conclusions These findings support docosahexaenoic acid as an atheroprotective macronutrient, whereas null findings for n-6 FAs challenge the view that they promote atherosclerosis.