APOE and Hypercholesterolemia: Studies with APOE2/3 isoforms have detected their protective effect for hypercholesterolemia, ischemic heart disease, and stroke, but APOE2/2 revealed an increased risk of vascular disease, thromboembolism, and arterial aneurysm, indicating that genetic variations in APOE do play a role in CVD risk [133,140,159,196].