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Revisiting elevated HDL cholesterol, cerebral hemodynamic improvement in asymptomatic carotid artery disease: A

Yorito Hattori1, Soichro Abe2, Yoshinori Kakino2

  • 1Department of Neurology, National Cerebral and Cardiovascular Center, Suita, Japan; Department of Preemptive Medicine for Dementia, National Cerebral and Cardiovascular Center, Suita, Japan.

Neurotherapeutics : the Journal of the American Society for Experimental Neurotherapeutics
|February 6, 2026
PubMed

Insights

High blood high-density lipoprotein cholesterol (HDL-C) levels predict improved cerebral hemodynamics in patients with carotid artery disease. This suggests HDL-C may be a therapeutic target for preventing ischemic stroke by enhancing blood flow.

Area of Science:

  • Neurology
  • Cardiovascular Medicine
  • Metabolic Research

Background:

  • Low high-density lipoprotein cholesterol (HDL-C) is linked to cerebrocardiovascular disease risk.
  • Interventional trials with HDL-C-raising drugs have not consistently improved cardiovascular outcomes.
  • Experimental studies suggest HDL-C promotes angiogenesis and arteriogenesis.

Purpose of the Study:

  • To investigate if high blood HDL-C levels predict cerebral hemodynamic improvements in patients with asymptomatic carotid artery stenosis/occlusion and cerebral hypoperfusion.
  • To explore the role of HDL-C in modulating cerebral blood flow and oxygen metabolism.

Main Methods:

  • Longitudinal retrospective observational study of 66 hemispheres in patients with asymptomatic carotid artery stenosis/occlusion.
  • Two-time multi-parametric 15O-gas positron emission tomography (PET) to assess cerebral blood flow (CBF), cerebral blood volume (CBV), and oxygen extraction fraction (OEF).
  • Comparison of hemodynamic parameter changes between patients with high and low baseline HDL-C levels.

Main Results:

  • High blood HDL-C levels were an independent predictor of increased CBF and CBV in the anterior circulation territory.
  • High HDL-C levels predicted a decrease in OEF.
  • A high blood HDL-C level was a clinical predictor of cerebral hemodynamic improvement.

Conclusions:

  • High blood HDL-C levels are associated with improved cerebral hemodynamics in patients with asymptomatic carotid artery stenosis/occlusion and hypoperfusion.
  • HDL-C may be a potential therapeutic target for ischemic stroke prevention through enhancement of cerebral hemodynamic parameters, possibly via angiogenesis and arteriogenesis.
  • Further research into HDL-C's role in cerebrovascular health is warranted.

Keywords:
(15)O-gas PETCarotid artery occlusionCarotid artery stenosisCerebral blood flowHigh-density lipoprotein cholesterol

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