Extent and severity of atherosclerotic involvement of the aortic valve androot in familial hypercholesterolaemia

Objective-To compare the frequency of valvar and supravalvar aortic stenosi s in homozygous and heterozygous familial hypercholesterolaemia (FH). Design-Analysis of life time cholesterol exposure and prevalence of aortic atherosclerosis in 84 consecutive cases attending a lipid clinic. Setting-A tertiary referral centre in London. Patients-Outpatients with FH (six homozygous, 78 heterozygous). Interventio ns-Maintenance of lipid lowering treatment. Main outcome measures-Calculated cholesterol x years score (CYS) and echoca rdiographic measurement of aortic root diameter, aortic valve thickness, an d transaortic gradient. Results-Four homozygotes with a mean (SD) CYS of 387 (124) mmol/l x years h ad severe aortic stenosis (treatment started after seven years of age), whe reas the other two had echocardiographic evidence of supravalvar thickening but no aortic valve stenosis (treatment started before three years of age) . On multivariate analysis, mean transaortic gradient correlated significan tly with CYS (mean = 523 (175) mmol/l x years) in heterozygotes (p = 0.0001 ), but only two had severe aortic valve and root involvement. Conclusions-In patients with familial hypercholesterolaemia, aortic stenosi s is common in homozygotes, and aortic root involvement is always present d espite the lower CYS than in heterozygotes. It appears to be determined by short term exposure to high cholesterol concentrations in early life. Conve rsely, aortic root and valve involvement are rare in heterozygotes and occu r only with severe, prolonged hypercholesterolaemia, possibly accelerating age related degenerative effects.