Exponential Relationship between Plasma Cholesterol Levels and Atherosclerotic Lesion Size in Hyperlipidemic Swine

Abstract

The effect of fish oil supplements on atherogenesis is controversial, especially when fish oil does not lower plasma cholesterol. Some studies in swine have shown that a fish oil supplement to a butter-cholesterol diet reduces atherogenesis. The fish oil supplement also frequently reduces average plasma cholesterol levels. The reduction in lesion size has been shown to be greater than can be expected from average plasma cholesterol reductions, if a linear relationship between lesion size and plasma cholesterol was assumed. However, in an experiment in which we equalized time-weighted average plasma cholesterol levels, there was no significant reduction in lesion size in the fish oil supplemented group. This led us to question the validity of the linear relationship between lesion size and plasma cholesterol level. In this study we have combined the results of eight study blocks with a total of 76 swine fed a similar hyperlipidemic, butter-cholesterol diet. Of these, 24 received a fish oil supplement (BT + fish oil) and 52 swine received no fish oil supplement (BT). The average lesion size as measured by nuclear profiles per cross section of a fixed site in the abdominal aorta (ABNpCx) was 7704 ± 778 (mean ± SEM) for the BT group and 2360 ± 1145 for the BT + fish oil group. Total plasma cholesterol levels were measured at the outset and at monthly intervals until sacrifice. For each animal we obtained a time-weighted average based on the trapezoidal rule. The average of all animals of the time-weighted average plasma cholesterol level was 630 ± 19 mg/dl for the BT group and 486 ± 27 mg/dl for the BT + fish oil group. Using the so-called Box-Cox method for transformation on the combined data set, we show that an exponential relationship between ABNpCx and time-weighted average plasma cholesterol level is a highly appropriate model and significant ( P < 0.0001). Neither the fish oil nor the block effect on lesion size is significant above and beyond the differences that might be due to plasma cholesterol levels.