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Endogenous Cholesterol Excretion Is Negatively Associated With Carotid Intima-Media Thickness in Humans.

Xiaobo Lin1, Susan B Racette1, Lina Ma1

  • 1From the Division of Endocrinology, Metabolism, and Lipid Research, Department of Medicine (X.L., S.B.R., L.M., R.E.O.), Program in Physical Therapy (S.B.R.), Division of Biostatistics (M.W.), and Cardiovascular Imaging and Clinical Research Core Laboratory, Cardiovascular Division, Department of Medicine (V.G.D.-R.), Washington University School of Medicine, St. Louis, MO.

Arteriosclerosis, Thrombosis, and Vascular Biology
|October 7, 2017
PubMed
Summary

Fecal excretion of endogenous cholesterol is protective against atherosclerosis, independent of cholesterol levels. Higher cholesterol excretion is linked to reduced carotid intima-media thickness, suggesting a role for reverse cholesterol transport in cardiovascular disease risk.

Keywords:
atherosclerosiscarotid intima-media thicknesscholesterolclinical trialmass spectrometry

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Area of Science:

  • Cardiovascular Disease Research
  • Cholesterol Metabolism
  • Atherosclerosis Studies

Background:

  • Lipid factors beyond LDL cholesterol significantly impact cardiovascular disease (CVD) risk.
  • Mobilization and excretion of cholesterol are crucial determinants of CVD risk.
  • Circulating lipoproteins represent only a small fraction of total body cholesterol.

Purpose of the Study:

  • To investigate the hypothesis that fecal excretion of endogenous cholesterol is protective against atherosclerosis.
  • To determine the relationship between cholesterol metabolism, fecal excretion, and carotid intima-media thickness.
  • To explore the role of reverse cholesterol transport in cardiovascular health.

Main Methods:

  • Quantified cholesterol metabolism and carotid intima-media thickness in 86 nondiabetic adults.
  • Utilized stable isotope labeling (cholesterol-d7, cholesterol-d5) to trace plasma and dietary cholesterol.
  • Employed mass spectrometry for analysis of plasma and stool samples under a controlled diet.

Main Results:

  • Carotid intima-media thickness was negatively correlated with fecal excretion of endogenous cholesterol (r=-0.426, P<0.0001).
  • Percent cholesterol absorption was positively correlated with intima-media thickness (r=+0.279, P=0.0092).
  • Fecal excretion of endogenous cholesterol remained a significant predictor of intima-media thickness in regression models (P=0.0008).

Conclusions:

  • Endogenous cholesterol excretion is independently and negatively associated with carotid intima-media thickness.
  • The intestine and cholesterol pools may represent an unrecognized CVD risk factor.
  • Further research is needed to link reverse cholesterol transport measures to atherosclerotic disease.