The effects of lovastatin and simvastatin on the diurnal periodicity of plasma mevalonate concentrations in patients with heterozygous familial hypercholesterolemia

Anuradha Pappu, D. Roger Illingworth

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Animal and human studies have shown that the biosynthesis of cholesterol exhibits diurnal periodicity with nocturnal increases in the level of cholesterol precursors. Dietary cholesterol, which increases the intracellular pool of cholesterol and plasma cholesterol levels, has been shown to blunt the nocturnal increases in cholesterol biosynthesis. Patients with heterozygous familial hypercholesterolemia (FH) have very high levels of plasma low-density lipoprotein cholesterol (LDL) due to their reduced ability to metabolize LDL particles. The present studies were carried out to determine whether diurnal variations in cholesterol synthesis occur in FH patients and to test the effects of 3-hydroxy-3-methyl glutaryl CoA (HMG CoA) reductase inhibitors on the diurnal cycle of cholesterol biosynthesis in these patients. Diurnal rates of cholesterol synthesis were assessed by measuring the plasma concentrations of mevalonate, an intermediate in the pathway of cholesterol biosynthesis. Female FH patients exhibited a diurnal pattern in plasma mevalonate levels similar to that previously reported in controls with peak values occurring at night. Treatment with lovastatin and simvastatin (40 mg b.i.d.) significantly reduced 24-h mean plasma mevalonate levels from baseline values. Administration of lovastatin in the evening reduced the nocturnal increases in mevalonate levels, and the administration of simvastatin completely abolished the nighttime rise. These results demonstrate that inhibition of cholesterol biosynthesis by lovastatin and simvastatin modifies the normal diurnal rhythm of cholesterol biosynthesis in female FH patients.

Original languageEnglish (US)
Pages (from-to)137-144
Number of pages8
JournalAtherosclerosis
Volume165
Issue number1
DOIs
StatePublished - Nov 2002

Fingerprint

Lovastatin
Mevalonic Acid
Hyperlipoproteinemia Type II
Simvastatin
Periodicity
Cholesterol
LDL Cholesterol
Dietary Cholesterol
Circadian Rhythm
Oxidoreductases

Keywords

  • Cholesterol synthesis
  • Familial hypercholesterolemia
  • Lovastatin
  • Mevalonic acid
  • Simvastatin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

@article{5aa7056e1b09413c8f762679e7462836,
title = "The effects of lovastatin and simvastatin on the diurnal periodicity of plasma mevalonate concentrations in patients with heterozygous familial hypercholesterolemia",
abstract = "Animal and human studies have shown that the biosynthesis of cholesterol exhibits diurnal periodicity with nocturnal increases in the level of cholesterol precursors. Dietary cholesterol, which increases the intracellular pool of cholesterol and plasma cholesterol levels, has been shown to blunt the nocturnal increases in cholesterol biosynthesis. Patients with heterozygous familial hypercholesterolemia (FH) have very high levels of plasma low-density lipoprotein cholesterol (LDL) due to their reduced ability to metabolize LDL particles. The present studies were carried out to determine whether diurnal variations in cholesterol synthesis occur in FH patients and to test the effects of 3-hydroxy-3-methyl glutaryl CoA (HMG CoA) reductase inhibitors on the diurnal cycle of cholesterol biosynthesis in these patients. Diurnal rates of cholesterol synthesis were assessed by measuring the plasma concentrations of mevalonate, an intermediate in the pathway of cholesterol biosynthesis. Female FH patients exhibited a diurnal pattern in plasma mevalonate levels similar to that previously reported in controls with peak values occurring at night. Treatment with lovastatin and simvastatin (40 mg b.i.d.) significantly reduced 24-h mean plasma mevalonate levels from baseline values. Administration of lovastatin in the evening reduced the nocturnal increases in mevalonate levels, and the administration of simvastatin completely abolished the nighttime rise. These results demonstrate that inhibition of cholesterol biosynthesis by lovastatin and simvastatin modifies the normal diurnal rhythm of cholesterol biosynthesis in female FH patients.",
keywords = "Cholesterol synthesis, Familial hypercholesterolemia, Lovastatin, Mevalonic acid, Simvastatin",
author = "Anuradha Pappu and Illingworth, {D. Roger}",
year = "2002",
month = "11",
doi = "10.1016/S0021-9150(02)00192-2",
language = "English (US)",
volume = "165",
pages = "137--144",
journal = "Atherosclerosis",
issn = "0021-9150",
publisher = "Elsevier Ireland Ltd",
number = "1",

}

TY - JOUR

T1 - The effects of lovastatin and simvastatin on the diurnal periodicity of plasma mevalonate concentrations in patients with heterozygous familial hypercholesterolemia

AU - Pappu, Anuradha

AU - Illingworth, D. Roger

PY - 2002/11

Y1 - 2002/11

N2 - Animal and human studies have shown that the biosynthesis of cholesterol exhibits diurnal periodicity with nocturnal increases in the level of cholesterol precursors. Dietary cholesterol, which increases the intracellular pool of cholesterol and plasma cholesterol levels, has been shown to blunt the nocturnal increases in cholesterol biosynthesis. Patients with heterozygous familial hypercholesterolemia (FH) have very high levels of plasma low-density lipoprotein cholesterol (LDL) due to their reduced ability to metabolize LDL particles. The present studies were carried out to determine whether diurnal variations in cholesterol synthesis occur in FH patients and to test the effects of 3-hydroxy-3-methyl glutaryl CoA (HMG CoA) reductase inhibitors on the diurnal cycle of cholesterol biosynthesis in these patients. Diurnal rates of cholesterol synthesis were assessed by measuring the plasma concentrations of mevalonate, an intermediate in the pathway of cholesterol biosynthesis. Female FH patients exhibited a diurnal pattern in plasma mevalonate levels similar to that previously reported in controls with peak values occurring at night. Treatment with lovastatin and simvastatin (40 mg b.i.d.) significantly reduced 24-h mean plasma mevalonate levels from baseline values. Administration of lovastatin in the evening reduced the nocturnal increases in mevalonate levels, and the administration of simvastatin completely abolished the nighttime rise. These results demonstrate that inhibition of cholesterol biosynthesis by lovastatin and simvastatin modifies the normal diurnal rhythm of cholesterol biosynthesis in female FH patients.

AB - Animal and human studies have shown that the biosynthesis of cholesterol exhibits diurnal periodicity with nocturnal increases in the level of cholesterol precursors. Dietary cholesterol, which increases the intracellular pool of cholesterol and plasma cholesterol levels, has been shown to blunt the nocturnal increases in cholesterol biosynthesis. Patients with heterozygous familial hypercholesterolemia (FH) have very high levels of plasma low-density lipoprotein cholesterol (LDL) due to their reduced ability to metabolize LDL particles. The present studies were carried out to determine whether diurnal variations in cholesterol synthesis occur in FH patients and to test the effects of 3-hydroxy-3-methyl glutaryl CoA (HMG CoA) reductase inhibitors on the diurnal cycle of cholesterol biosynthesis in these patients. Diurnal rates of cholesterol synthesis were assessed by measuring the plasma concentrations of mevalonate, an intermediate in the pathway of cholesterol biosynthesis. Female FH patients exhibited a diurnal pattern in plasma mevalonate levels similar to that previously reported in controls with peak values occurring at night. Treatment with lovastatin and simvastatin (40 mg b.i.d.) significantly reduced 24-h mean plasma mevalonate levels from baseline values. Administration of lovastatin in the evening reduced the nocturnal increases in mevalonate levels, and the administration of simvastatin completely abolished the nighttime rise. These results demonstrate that inhibition of cholesterol biosynthesis by lovastatin and simvastatin modifies the normal diurnal rhythm of cholesterol biosynthesis in female FH patients.

KW - Cholesterol synthesis

KW - Familial hypercholesterolemia

KW - Lovastatin

KW - Mevalonic acid

KW - Simvastatin

UR - http://www.scopus.com/inward/record.url?scp=0036841917&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036841917&partnerID=8YFLogxK

U2 - 10.1016/S0021-9150(02)00192-2

DO - 10.1016/S0021-9150(02)00192-2

M3 - Article

VL - 165

SP - 137

EP - 144

JO - Atherosclerosis

JF - Atherosclerosis

SN - 0021-9150

IS - 1

ER -