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The possibility that low high density lipoprotein (HDL) levels may add to the risk of occlusive atherosclerosis in familial hypercholesterolemia (FH) is supported by the frequency and severity of this finding in these patients, particularly homozygotes. To investigate this abnormality in greater detail, we measured HDL lipid and apoprotein values in nine homozygotes with FH. Compared to their unaffected relatives, they had markedly reduced HDL cholesterol and apo A-I and A-II levels. The values found in heterozygote relatives were between those of homozygotes and those of controls. Density gradient ultracentrifugation of serum or isolated HDL from homozygotes demonstrated little or no HDL2; there was also a shift of homozygotes' HDL to an above normal peak density (d = 1.15 g/ml). Heterozygotes had milder abnormalities. The reduced HDL in FH seems to be related to elevated low density lipoprotein levels although the pathophysiology is unknown. These findings add weight to the concept that HDL abnormalities contribute to the relentless course of atherosclerosis in familial hypercholesterolemia.

Abnormalities of high density lipoproteins in homozygous familial hypercholesterolemia.