Assessment of microvascular function and pharmacological regulation in genetically confirmed familial hypercholesterolemia

Microvasc Res. 2021 Nov:138:104216. doi: 10.1016/j.mvr.2021.104216. Epub 2021 Jun 26.

Abstract

Background: Familial hypercholesterolemia (FH) is a genetic lipid disorder leading to accelerated atherosclerosis, premature cardiovascular disease and death. Microvascular endothelial dysfunction is one of the earliest vascular pathology manifestations and may precede symptomatic atherosclerosis.

Methods: In this paper, microvascular endothelial function was assessed in FH patients and healthy controls using flow mediated skin fluorescence (FMSF), based on measurements of nicotinamide adenine dinucleotide fluorescence intensity during brachial artery occlusion (ischemic response, IR) and immediately after occlusion (hyperemic response, HR). Low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) were used to assess its relation with microvascular parameters evaluated in vivo.

Results: LDL-C levels were significantly correlated to both HRmax (r = -0.548, p = 0.001) and HRindex (r = -0.514, p = 0.003). Similarly, there was a significant inverse correlation of TC levels and both HRmax (r = -0.538, p = 0.002) and HRindex (r = -0.512, p = 0.003). All FMSF parameters were found lower in FH patients compared to age- and sex-matched healthy controls. Hyperemic response (HRmax) was significantly higher in FH patients examined on statins compared to those without any lipid-lowering treatment (19.9 ± 3.1 vs. 16.4 ± 4.2 respectively, p = 0.022).

Conclusions: This study shows that, in patients with FH, microvascular endothelial-dependent hyperemic response is impaired and inversely correlated to plasma cholesterol levels. Microvascular function was found better in FH patients receiving statins.

Keywords: Endothelium; Familial hypercholesterolemia; Flow mediated skin fluorescence; Microcirculation; NADH fluorescence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • Case-Control Studies
  • Cholesterol / blood*
  • Cholesterol, LDL / blood
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hyperemia / physiopathology
  • Hyperlipoproteinemia Type II / blood
  • Hyperlipoproteinemia Type II / drug therapy*
  • Hyperlipoproteinemia Type II / genetics
  • Hyperlipoproteinemia Type II / physiopathology
  • Male
  • Microcirculation / drug effects*
  • Microvessels / drug effects*
  • Microvessels / physiopathology
  • Middle Aged
  • Phenotype
  • Skin / blood supply*
  • Treatment Outcome

Substances

  • Biomarkers
  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Cholesterol