Vascular inflammation and metabolic activity in hematopoietic organs and liver in familial combined hyperlipidemia and heterozygous familial hypercholesterolemia

J Clin Lipidol. 2018 Jan-Feb;12(1):33-43. doi: 10.1016/j.jacl.2017.10.019. Epub 2017 Nov 2.

Abstract

Background: Familial dyslipidemias of either heterozygous (heFH) or combined (FCH) type lead to accelerated atherogenesis and increased cardiovascular risk.

Objective: The aim of this study was to investigate in statin-naïve adult patients with familial dyslipidemias whether inflammatory activation and liver, spleen and bone marrow metabolic activity differ compared with normolipidemic subjects and between dyslipidemic groups.

Methods: Fourteen patients with FCH, 14 with heFH, and 14 normolipidemic individuals were enrolled. Serum lipids, high-sensitivity C-reactive protein, and fibrinogen levels were measured, followed by 18F-fluorodeoxyglucose positron-emission tomography/computed tomography imaging. Radiotracer uptake in the aortic wall, spleen, bone marrow, and liver was quantified as tissue-to-background ratio (TBR).

Results: Patients with heFH had significantly higher low-density lipoprotein levels compared with those with FCH and controls (P < .001). However, aortic TBRs were higher in FCH compared with heFH patients and controls (P = .02 and P < .001, respectively). FCH patients exhibited higher FDG uptake in the spleen compared with controls (P = .05). In addition, FCH exhibited higher bone marrow FDG uptake compared with heFH patients and controls (P = .03 and P = .02, respectively). FCH had higher liver uptake compared with heFH patients and controls (P < .001 for both). Significant correlations were observed between inflammatory biomarkers and imaging indices as well as between aortic TBR and FDG uptake of hematopoietic organs and liver.

Conclusions: Systemic, as well as vascular inflammation and spleen, bone marrow, and hepatic metabolic activity are increased in patients with FCH despite lower levels of low-density lipoprotein.

Keywords: (18)FDG PET/CT; Bone marrow; Familial dyslipidemias; Spleen; Vascular inflammation.

MeSH terms

  • Adult
  • Biomarkers / blood
  • Bone Marrow / diagnostic imaging
  • Bone Marrow / metabolism*
  • C-Reactive Protein / analysis
  • Case-Control Studies
  • Female
  • Heterozygote
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Hyperlipidemia, Familial Combined / drug therapy
  • Hyperlipidemia, Familial Combined / metabolism
  • Hyperlipidemia, Familial Combined / pathology*
  • Hyperlipoproteinemia Type II / drug therapy
  • Hyperlipoproteinemia Type II / metabolism
  • Hyperlipoproteinemia Type II / pathology*
  • Inflammation / metabolism
  • Lipoproteins, LDL / blood
  • Liver / diagnostic imaging
  • Liver / metabolism*
  • Male
  • Middle Aged
  • Positron Emission Tomography Computed Tomography
  • Spleen / diagnostic imaging
  • Spleen / metabolism*

Substances

  • Biomarkers
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipoproteins, LDL
  • C-Reactive Protein