Morphological Characteristics of Aortic Stenosis in Familial Hypercholesterolemia and Non-Familial Hypercholesterolemia in the Elderly

Background: Patients with familial hypercholesterolemia are known to have an extremely high risk of coronary artery disease owing to high levels of low-density lipoprotein-cholesterol since birth. In addition, aortic stenosis among patients with familial hypercholesterolemia has also been reported besides coronary disease. The aim of this study was to characterize the histopathological differences in excised aortic valves for aortic stenosis between patients with familial hypercholesterolemia and non-familial hypercholesterolemia. Subjects and Methods: Six familial patients (3 homozygous, 3 heterozygous familial hypercholesterolemia patients), and 18 non-familial hypercholesterolemia patients underwent pathological and immunohistochemical examinations for aortic valves macroscopically and microscopically at aortic valve replacement surgery for stenosis. Results: Our study revealed that calcification of aortic valves among homozygous hypercholesterolemia showed a much milder degree than those of non-familial patients. Moreover, the age at surgery for stenosis in the case of homozygotes was significantly less than that of heterozygous hypercholesterolemia and nonfamilial hypercholesterolemia patients. In addition, CD68-positive macrophages infiltrated the aorta side (fibrosa) in all familial hypercholesterolemia patients. However, the macrophage accumulation in the aortic valves of non-familial hypercholesterolemia patients was recognized in the middle layer (spongiosa) near calcification and left ventricular side (ventricularis) of the aortic valves. Conclusion: Lipid is one of the important factors for aortic valve fibrosis and stenosis in hypercholesterolemia. This study suggested that the non-familial atherosclerotic aortic stenosis in the elderly is qualitatively different from aortic valves in familial hypercholesterolemia, primarily owing to calcification resulting from age and long-term degeneration and inflammatory responses.