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Characteristic cardiovascular manifestation in homozygous and heterozygous familial hypercholesterolemia
A Kawaguchi1, K Miyatake, C Yutani
1Department of Etiology and Pathophysiology, National Cardiovascular Center, Research Institute and Hospital, Osaka, Japan.
Insights
Familial hypercholesterolemia (FH) significantly impacts the aortic root and valve, leading to premature atherosclerosis. This "hypercholesterolemic valvulopathy" is particularly pronounced in homozygous FH patients, affecting aortic function.
Area of Science:
- Cardiovascular Medicine
- Genetics
- Pathology
Background:
- Familial hypercholesterolemia (FH) is known to affect coronary arteries.
- Aortic valve dysfunction in homozygous FH patients suggests broader cardiovascular impact.
- This study investigates aortic root and valve involvement in FH.
Purpose of the Study:
- To characterize premature atherosclerotic lesions in the aortic root of patients with homozygous and heterozygous FH.
- To assess aortic valve function and structure in FH patients.
- To compare FH patients with normocholesterolemic controls.
Main Methods:
- Histopathologic examination of aortic root specimens.
- Cardiac catheterization and angiography in homozygous FH patients.
- Color Doppler echocardiography in heterozygous FH patients and controls.
- Measurement of aortic annulus diameter and aortic ridge dynamics.
Main Results:
- 80% of homozygous FH patients showed aortic regurgitation; 30% had significant pressure gradients.
- 80% of homozygous FH patients exhibited coronary ostia stenosis.
- Aortic regurgitation was more prevalent in heterozygous FH patients (10/39) than controls (1/30).
- Reduced aortic diameter and distensibility were observed in heterozygous FH patients.
- Aortic valve cusp thickening and foam cell infiltration were noted in FH patients.
Conclusions:
- Premature atherosclerosis in FH predominantly affects the aortic root.
- Aortic valve involvement, termed "hypercholesterolemic valvulopathy," is a key feature of FH, especially homozygous forms.
- Hypercholesterolemia's detrimental effects extend to the aortic valve, mirroring its impact on coronary arteries.
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 patients with heterozygous FH to characterize the premature atherosclerotic lesions by using histopathologic specimens.
Methods And Results:
The aortic roots of 10 patients with homozygous FH, age 9 to 58 years, were studied by cardiac catheterization with several angiographies. The aortic roots of 39 patients with heterozygous FH under age 60 years were also examined for aortic and mitral valvular functions by color Doppler echocardiography, and 30 normocholesterolemic patients with coronary artery disease were examined as control subjects. In addition, in 22 patients with FH and 20 control subjects, the internal diameter of the aortic annulus and the aortic ridge in cardiac cycles were measured. Of the 10 homozygotes with FH, 8 patients had aortic regurgitation demonstrated by aortography; 3 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 heterozygotes with FH, 10 patients had aortic regurgitation shown by Doppler echocardiography, as did only 1 of the 30 control subjects (P <.05). The average diameter and distensibility of the ascending aorta were significantly reduced in the heterozygotes compared with the control subjects. The surgically resected cusp specimens of aortic valves obtained from 1 homozygous and 1 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 caused by hypercholesterolemia.