Relationship between plasma coenzyme Q10, asymmetric dimethylarginine and arterial stiffness in patients with phenotypic or genotypic familial hypercholesterolemia on long-term statin therapy

Atherosclerosis. 2011 Sep;218(1):188-93. doi: 10.1016/j.atherosclerosis.2011.04.034. Epub 2011 May 5.

Abstract

Objective: We investigated whether statin-treated heterozygous familial hypercholesterolemic (FH) patients have lower plasma coenzyme Q(10) (CoQ(10)) levels than low-density lipoprotein receptor (LDLR) mutation negative FH patients on equivalent statin doses, and whether lower CoQ(10) concentrations are associated with increased arterial stiffness.

Methods: Thirty LDLR mutation negative patients with clinical FH and 30 mutation positive FH patients matched for gender, statin duration and dose, and a further 30 controls were studied. Plasma CoQ(10) and asymmetric dimethylarginine (ADMA) levels were measured by HPLC and the augmentation index by pulse wave analysis.

Results: Plasma CoQ(10) levels, and the ratios of CoQ(10) to total cholesterol and LDL-cholesterol were similar in treated FH patients with identified LDLR mutations to mutation negative patients on equivalent doses of statin therapy (p>0.05). CoQ(10) and lipid levels were also comparable to controls not using any lipid modifying treatment. Arterial stiffness was higher in mutation negative patients (p=0.04) and there was a trend for an increase in mutation positive patients (p=0.09). ADMA was higher in the mutation positive group (p<0.01). The augmentation index corrected for age, blood pressure, and heart rate, was negatively correlated with plasma CoQ(10) within FH patients (p<0.05).

Conclusion: Long-term, high-dose statin therapy does not lead to subnormal CoQ(10) concentrations in patients with phenotypic or genotypic FH. Arterial stiffness is elevated in FH patients compared to untreated controls, and low CoQ(10) levels are associated with increased arterial stiffness. CoQ(10) supplementation trials are warranted in FH patients.

MeSH terms

  • Aged
  • Arginine / analogs & derivatives*
  • Arginine / blood
  • Arginine / genetics
  • Case-Control Studies
  • Chromatography, High Pressure Liquid / methods
  • Female
  • Genotype
  • Heterozygote
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Hyperlipoproteinemia Type II / blood*
  • Hyperlipoproteinemia Type II / drug therapy*
  • Hyperlipoproteinemia Type II / genetics
  • Male
  • Middle Aged
  • Mutation
  • Receptors, LDL / genetics
  • Ubiquinone / analogs & derivatives*
  • Ubiquinone / blood
  • Ubiquinone / genetics
  • Vascular Stiffness*

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Receptors, LDL
  • Ubiquinone
  • N,N-dimethylarginine
  • Arginine
  • coenzyme Q10