Relationship between urinary cGMP excretion and serum total cholesterol levels in a general population

Renzhe Cui1, Hiroyasu Iso, Jingbo Pi

  • 1Department of Public Health, Social and Environmental Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.

Atherosclerosis
|March 22, 2005
PubMed

Insights

High cholesterol impairs blood vessel function. This study found that higher total cholesterol levels, even within normal ranges, correlate with reduced nitric oxide (NO) bioactivity, indicated by lower urinary cyclic guanosine 3

Area of Science:

  • Cardiovascular Science
  • Endocrinology
  • Nephrology

Background:

  • Hypercholesterolemia is known to impair endothelial function, a critical component of cardiovascular health.
  • The specific threshold of serum total cholesterol at which endothelial dysfunction initiates remains undetermined.
  • Nitric oxide (NO) plays a vital role in maintaining endothelial function, and its bioactivity can be assessed via its second messenger, cyclic guanosine 3',5' monophosphate (cGMP).

Purpose of the Study:

  • To investigate the relationship between serum total cholesterol concentrations and urinary cGMP excretion in a general Japanese population.
  • To determine if elevated cholesterol levels, even within clinically normal ranges, are associated with reduced NO bioactivity.

Main Methods:

  • Cross-sectional study involving 1541 Japanese men and women aged 40-79 years.
  • Collected 24-hour urine samples to measure urinary cGMP excretion, adjusted for urinary creatinine.
  • Assessed serum total cholesterol levels and adjusted for age, sex, and cardiovascular risk factors.

Main Results:

  • A significant inverse linear correlation was observed between serum total cholesterol levels and urinary cGMP excretion (p=0.007).
  • Mean urinary cGMP excretion decreased progressively with increasing total cholesterol levels, starting from <4.14 mmol/L.
  • This inverse relationship was more pronounced in individuals with end-organ damage, higher C-reactive protein (CRP) levels, and postmenopausal women.

Conclusions:

  • Higher serum total cholesterol levels are associated with reduced nitric oxide bioactivity, even within clinically normal ranges.
  • This finding suggests a potential mechanism for endothelial dysfunction in hypercholesterolemia that may begin at lower cholesterol levels than previously thought.
  • Further research is warranted to elucidate the clinical implications of reduced NO bioactivity at varying cholesterol levels.

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