Effect of ezetimibe on low- and high-density lipoprotein subclasses in sitosterolemia.
Sitosterolemia displays high plasma total sterols [high plant sterols (PS) + normal to high total cholesterol (TC)] with normal to moderately elevated low-density lipoprotein (LDL) levels. High LDL, intermediate-density lipoprotein (IDL) and very low-density lipoprotein (VLDL) particles, low high-density lipoprotein (HDL), and increased non-HDL and the ratios of TC and triglycerides (TG) to HDL can increase the risk for atherosclerosis. Ezetimibe (EZE) can reduce plasma PS and TC levels in sitosterolemia, but its effect on lipoprotein subclasses has not been previously reported.



Sitosterolemia patients (n = 8) were taken off EZE for 14 weeks (OFF EZE) and placed on EZE (10 mg/d) for 14 weeks (ON EZE). Serum lipids were measured enzymatically and lipoprotein subclasses were assessed by polyacrylamide gel electrophoresis.



EZE reduced (p < 0.05) total sterols (-12.5 ± 4.1%) and LDL-sterol (-22.7 ± 5.7%) and its sterol mass of large VLDL (-24.4 ± 4.5%), VLDL remnants (-21.1 ± 7.9%) and large IDL (-22.4 ± 7.2%) compared to OFF EZE. EZE did not affect large LDL subclasses or mean LDL particle size (273.8 ± 0.6 vs. 274.6 ± 0.3 Å). EZE increased HDL-sterol (25.5 ± 8.0%, p = 0.008) including intermediate (34 ± 14%, p = 0.02) and large (33 ± 16%, p = 0.06) HDL. EZE reduced non-HDL-sterol (-21.8± 5.0%), total sterols/HDL (-28.2 ± 5.5%) and TG/HDL (-27.4 ± 6.5%, all p < 0.01).



EZE improves VLDL and HDL subfraction distribution, thereby reducing the atherogenic lipid profile, thus providing potential clinical benefit in sitosterolemia beyond TC and PS reduction.
Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada; Richardson Center for Functional Foods and Nutraceuticals, University of Manitoba, Winnipeg, Manitoba, Canada.
Rgia A
RA
Othman
Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada; Richardson Center for Functional Foods and Nutraceuticals, University of Manitoba, Winnipeg, Manitoba, Canada. Electronic address: myrie@cc.umanitoba.ca.
Semone B
SB
Myrie
Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
David
D
Mymin
College of Pharmacy, Washington State University, Spokane, WA, United States; Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, United States.
Jean-Baptiste
JB
Roullet
University of Wisconsin School of Medicine and Public Health, Madison, WI, United States.
Robert D
RD
Steiner
Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada; Richardson Center for Functional Foods and Nutraceuticals, University of Manitoba, Winnipeg, Manitoba, Canada.
Peter J H
PJH
Jones
D000293:Adolescent; D000328:Adult; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D008076:Cholesterol, HDL / Q000097:blood; D004591:Electrophoresis, Polyacrylamide Gel; D000069438:Ezetimibe / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D007410:Intestinal Diseases / Q000097:blood / Q000188:drug therapy*; D008052:Lipid Metabolism, Inborn Errors / Q000097:blood / Q000188:drug therapy*; D008075:Lipoproteins, HDL / Q000097:blood* / Q000187:drug effects; D053419:Lipoproteins, IDL / Q000097:blood / Q000187:drug effects; D008079:Lipoproteins, VLDL / Q000097:blood* / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010840:Phytosterols / Q000009:adverse effects* / Q000097:blood; D016896:Treatment Outcome; D055815:Young Adult
D000924:Anticholesteremic Agents; D008076:Cholesterol, HDL; D008075:Lipoproteins, HDL; D053419:Lipoproteins, IDL; D008079:Lipoproteins, VLDL; D010840:Phytosterols; D000069438:Ezetimibe
Ezetimibe; HDL subclasses; LDL cholesterol; LDL subclasses; Mean LDL particle size; Non-HDL cholesterol; Sitosterolemia; Sterols