Eliot A Brinton1, Paul N Hopkins2, Robert A Hegele3, Andrew S Geller4, Eliana Y Polisecki5, Margaret R Diffenderfer4, Ernst J Schaefer6. 1. Utah Lipid Center, Salt Lake City, UT, USA. 2. Division of Cardiovascular Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA. 3. London Regional Research Centre, Robarts Research Institute, University of Western Ontario, London, ON, Canada. 4. Boston Heart Diagnostics, Framingham, MA, USA; Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA. 5. Boston Heart Diagnostics, Framingham, MA, USA. 6. Boston Heart Diagnostics, Framingham, MA, USA; Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA. Electronic address: eschaefer@bostonheartdx.com.
Abstract
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 <130 mg/dL. Among all subjects, 0.050% had β-sitosterol levels ≥15.0 mg/L, consistent with sitosterolemia, while among those with LDL-C ≥190 mg/dL, 0.334% had this rare disorder. A 13-year-old boy with the highest LDL-C (679 mg/dL) of all subjects had planar xanthomas and a β-sitosterol level of 53.5 mg/L (normal <3.3 mg/L). He was a compound heterozygote for 2 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.
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 <130 mg/dL. Among all subjects, 0.050% had β-sitosterol levels ≥15.0 mg/L, consistent with sitosterolemia, while among those with LDL-C ≥190 mg/dL, 0.334% had this rare disorder. A 13-year-old boy with the highest LDL-C (679 mg/dL) of all subjects had planar xanthomas and a β-sitosterol level of 53.5 mg/L (normal <3.3 mg/L). He was a compound heterozygote for 2 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.
Authors: Andrew S Geller; Eliana Y Polisecki; Margaret R Diffenderfer; Bela F Asztalos; Sotirios K Karathanasis; Robert A Hegele; Ernst J Schaefer Journal: J Lipid Res Date: 2018-10-17 Impact factor: 5.922