Objective To compare the frequency of valvar and supravalvar aortic stenosis 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).

Interventions Maintenance of lipid lowering treatment.

Main outcome measures Calculated cholesterol × years score (CYS) and echocardiographic measurement of aortic root diameter, aortic valve thickness, and transaortic gradient.

Results Four homozygotes with a mean (SD) CYS of 387 (124) mmol/l × years had severe aortic stenosis (treatment started after seven years of age), whereas 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 significantly with CYS (mean = 523 (175) mmol/l × years) in heterozygotes (p = 0.0001), but only two had severe aortic valve and root involvement.

Conclusions In patients with familial hypercholesterolaemia, aortic stenosis is common in homozygotes, and aortic root involvement is always present despite the lower CYS than in heterozygotes. It appears to be determined by short term exposure to high cholesterol concentrations in early life. Conversely, aortic root and valve involvement are rare in heterozygotes and occur only with severe, prolonged hypercholesterolaemia, possibly accelerating age related degenerative effects.