Abstract 374: Soy Supplementation Prevents Progression of Smaller but Not Larger Atherosclerotic Plaques: Results of a Postmenopausal Monkey Reverse Translational Trial

Abstract

Rationale_ A recent clinical trial reported that soy supplementation reduced atherosclerosis progression in the carotid arteries of women who were <5 years postmenopausal, an effect not shared by women >5 years postmenopausal. Here we tested the hypothesis that soy atheroprotection may be influenced by the size of pre-existing atherosclerotic lesions at the initiation of treatment. Methods_ Premenopausal female cynomolgus macaques (n=38) were fed an atherogenic diet (Casein/Lactalbumin [CL]) for 34 months. Animals were then ovariectomized (OVX) and the left iliac artery (LCI, a surrogate for the coronary arteries) was biopsied to determine the amount of atherosclerosis present at baseline. Immediately after OVX, monkeys were randomized to either continue consuming the CL diet (n = 20) or to consume a soy protein diet (SP, n = 18) for an additional 34 months. At necropsy, the right iliac (RCI) and coronary arteries were collected and atherosclerosis extent was quantified. Results_ The CL diet group increased plaque size in the RCI compared to pretreatment (0.43 ± 0.06 mm 2 vs. 0.85 ± 0.12 mm 2 , p =0.019) whereas, plaques did not increase in size in the SP diet group, (LCI: 0.60 ± 0.10 mm 2 vs. RCI: 0.82 ± 0.16 mm 2 , p=0.17). Notably, SP diet did not have a beneficial effect on coronary artery plaque extent (CL: 0.73 ± 0.20 mm 2 vs. SP: 0.63 ± 0.16 mm 2 , p =NS). However, we observed that when animals were divided at the median based on pretreatment LCI plaque sizes (below; 0.21 ± 0.14 mm 2 : above; 0.82 ± 0.06 mm 2 ), the SP diet prevented plaque progression in both the iliac (CL: 0.54 ± 0.14 mm 2 vs. SP: 0.19 ± 0.04 mm 2 , p =0.04) and coronary arteries (CL: 0.52 ± 0.11 vs. SP: 0.17 ± 0.06 mm 2 , p =0.04) only in animals with smaller pretreatment plaques. There was no atheroinhibition among soy treated monkeys with plaques that were above the median (RCI CL: 1.32 ± 0.11 mm 2 vs. SP: 1.35 ± 0.14, p =0.94 and coronary artery CL: 1.06 ± 0.11 vs. Soy: 1.00 ± 0.17, p =0.63). Conclusions_ Pretreatment atherosclerosis stage is a major determinant of the potential atheroprotective effect of soy treatment. These data suggest that to obtain cardiovascular benefits of soy supplements, treatment should begin during the perimenopausal transition or in the very early postmenopause while plaques are usually still small.