The association between hypercholesterolemia and sitosterolemia, and report of a sitosterolemia kindred

Background Sitosterolemia is associated with increases in intestinal sterol absorption, low-density lipoprotein cholesterol (LDL-C), and cardiovascular disease risk. Objective We examined the relationship between hypercholesterolemia and sitosterolemia in a large population and report a new sitosterolemia case. Methods Plasma sterol concentrations were measured by gas chromatography/mass spectrometry, and LDL-C by direct assay. Results Of 207,926 subjects tested, 4.3% had LDL-C ≥190 mg/dL. Plasma β-sitosterol concentrations ≥8.0 mg/L (99th percentile) were found in 4.3% of these subjects vs 0.72% with LDL-C ABCG8 mutations (p.N409D and an intron 11+2T>A splice site mutation). On a low-cholesterol and plant-sterol diet, his LDL-C decreased to 485 mg/dL (−29%) and β-sitosterol to 44.6 mg/L (−27%). On atorvastatin 20 mg/d, his LDL-C decreased to 299 mg/dL (−38%). With added ezetimibe 10 mg/d, his LDL-C normalized to 60 mg/dL (−80% further decrease); and his β-sitosterol decreased to 14.1 mg/L (−68% further decrease). Conclusions Our data indicate that about 4% of subjects with LDL-C concentrations ≥190 mg/dL have plasma β-sitosterol concentrations above the 99th percentile and about 0.3% have concentrations consistent with sitosterolemia. Therefore, this diagnosis should be considered in such patients.