n-3 and n-6 Fatty acids are independently associated with lipoprotein-associated phospholipase A2 in the Multi- Ethnic Study of Atherosclerosis

Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is an independent risk factor for CVD and has been proposed as a marker of vascular inflammation. Polyunsaturated n-3 fatty acids (FA) and several n-6 FA are known to suppress inflammation and may influence Lp-PLA(2) mass and activity. The associations of n-3 and n-6 plasma FA with Lp-PLA(2) mass and activity were analysed using linear regression analysis in 2246 participants of the Multi-Ethnic Study of Atherosclerosis; statistical adjustments were made to control for body mass, inflammation, lipids, diabetes, and additional clinical and demographic factors. Lp-PLA(2) mass and activity were significantly lower in participants with the higher n-3 FA EPA (beta=-4.72, P<0.001; beta= -1.53; P 0.023) and DHA levels (beta= -4.47, beta= -1.87; both P<0.001). Those in the highest quintiles of plasma EPA and DHA showed 12.71 and 19.15 ng/ml lower Lp-PLA(2) mass and 5.7 and 8.90 nmol/min per ml lower Lp-PLA(2) activity than those in the first quintiles, respectively. In addition, lower Lp-PLA(2) mass and activity were associated with higher levels of n-6 arachidonic acid (beta=-1.63, beta=-1.30; both P<0.001), while gamma-linolenic acid was negatively associated with activity (b 227.7, P=0.027). Lp-PLA(2) mass was significantly higher in participants with greater plasma levels of n-6 linoleic (beta= 0.828, P 0.011) and dihomo-gamma-linolenic acids (beta= 4.17, P=0.002). Based on their independent associations with Lp-PLA(2) mass and activity, certain n-3 and n-6 FA may have additional influences on CVD risk. Intervention studies are warranted to assess whether these macronutrients may directly influence Lp-PLA(2) expression or activity.