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Premature Valvular Heart Disease in Homozygous Familial Hypercholesterolemia
Akl C Fahed1, Kamel Shibbani2, Rabih R Andary2
1Division of Cardiology, Massachusetts General Hospital, Boston, MA, USA.
Insights
Valvular heart disease is common in familial hypercholesterolemia (FH). In homozygous FH patients, subclinical valvulopathy affects many, regardless of age or LDL levels, and is not significantly impacted by lipid-lowering treatments.
Area of Science:
- Cardiology
- Genetics
- Metabolic Disorders
Background:
- Familial hypercholesterolemia (FH) is linked to premature atherosclerosis and valvular heart disease.
- Research on valvular disease in heterozygous FH is more extensive than in homozygous FH.
- Homozygous FH presents a unique challenge due to extremely high low-density lipoprotein (LDL) levels from birth.
Purpose of the Study:
- To investigate the incidence and characteristics of subclinical valvulopathy in patients with homozygous FH.
- To assess the relationship between age, LDL levels, and valvular disease in this population.
- To determine the influence of lipid-lowering treatments, including LDL apheresis, on valvular disease progression.
Main Methods:
- Echocardiographic studies were conducted on 33 young patients with homozygous FH (mean age 26 years).
- Patients had a mean LDL level of 447 mg/dL, with 73% undergoing LDL apheresis.
- Valvular function, aortic valve calcification, and mitral regurgitation were assessed.
Main Results:
- Twenty-one out of 33 patients (64%) showed evidence of valvulopathy in the aortic or mitral valves.
- Seven subjects exhibited significant mitral regurgitation.
- Older patients (>21 years) were more likely to have aortic valve calcification (59% vs. 12.5%, p=0.01), despite lower study LDL levels.
Conclusions:
- Valvulopathy is prevalent in homozygous FH patients across a broad age range and varying LDL levels.
- Lipid-lowering treatments appear to have a limited impact on the development of valvular disease in this cohort.
- Echocardiography is a valuable tool for monitoring subclinical valvular heart disease in homozygous FH.
Abstract:
Valvular heart disease frequently occurs as a consequence of premature atherosclerosis in individuals with familial hypercholesterolemia (FH). Studies have primarily focused on aortic valve calcification in heterozygous FH, but there is paucity of data on the incidence of valvular disease in homozygous FH. We performed echocardiographic studies in 33 relatively young patients (mean age: 26 years) with homozygous FH (mean LDL of 447 mg/dL, 73% on LDL apheresis) to look for subclinical valvulopathy. Twenty-one patients had evidence of valvulopathy of the aortic or mitral valves, while seven subjects showed notable mitral regurgitation. Older patients were more likely to have aortic valve calcification (>21 versus ≤21 years: 59% versus 12.5%; p = 0.01) despite lower LDL levels at the time of the study (385 versus 513 mg/dL; p = 0.016). Patients with valvulopathy were older and had comparable LDL levels and a lower carotid intima-media thickness. Our data suggests that, in homozygous FH patients, valvulopathy (1) is present across a wide age spectrum and LDL levels and (2) is less likely to be influenced by lipid-lowering treatment. Echocardiographic studies that focused on aortic root thickening and stenosis and regurgitation are thus likely an effective modality for serial follow-up of subclinical valvular heart disease.
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