Characteristic cardiovascular manifestation in homozygous and heterozygous familial hypercholesterolemia

Background The aortic valve dysfunction of patients with homozygous familial hypercholesterolemia (FH) suggests that hypercholesterolemia affects not only coronary arteries, but also the aortic valve. We studied the aortic root of patients with homozygous FH and those of heterozygous FH to characterize the premature atherosclerotic lesions, using histopathological specimens. Methods and results The aortic roots of 10 homozygous FH patients, aged 9 to 58 years, were studied by cardiac catheterization with several angiographies. The aortic root of 39 heterozygous FH patients under age 60 were also examined for aortic and mitral valvular functions by color Doppler echocardiography, and 30 normocholesterolemic patients with coronary artery disease were examined as controls. In addition, in 22 FH and 20 control subjects, the internal diameter of the aortic annulus and the aortic ridge in cardiac cycles were measured. Of the 10 FH homozygotes, 8 patients had aortic regurgitation demonstrated by aortography; three of them showed significant transvalvular pressure gradients. Stenotic changes of coronary ostia were observed in 8 of the 10 homozygotes with moderate coronary atherosclerosis. Of the 39 FH heterozygotes, ten patients had aortic regurgitation shown by Doppler echocardiography, as did only one of the 30 control subjects (P<0.05). The average diameter and distensibility of the ascending aorta were significantly reduced in the heterozygotes compared to the control subjects. The surgically resected cusp specimens of aortic valves obtained from one homozygous and one heterozygous patient showed significant thickening of the cusp with foam cell infiltration. Conclusions Premature atherosclerosis in FH had a characteristic distribution, affecting the aortic root dominantly. The involvement of the aortic valve indicating “hypercholesterolemic valvulopathy” was a peculiar feature of FH, especially its homozygous form, but was reminiscent of ubiquitous processes due to hypercholesterolemia