The Framingham Study is notable for yielding the observation that people who maintained a total serum cholesterol below 150 mg/dL were virtually immune to heart attack throughout their lives. This suggests that, while other factors are evidently involved, a certain minimal level of LDL cholesterol is a virtual sine qua non for progression of coronary disease. This view is consistent with the virtual absence of coronary disease in cultures where the average cholesterol is well below 150.

In 1985, a surgeon at the Cleveland Clinic, Dr. Caldwell Esselstyn, sought to determine whether lowering cholesterol below the 150 threshold could half progression of coronary disease in patients with pre-existing coronary lesions and symptomatic heart disease. He was aware that the 10%-fat plant-base diet recommended by pritikin (and subsequently adopted by Ornish with Esselstyn's encouragement) could achieve substantial rapid reductions in serum cholesterol -but these reductions were often insufficient to break the 150 barrier.