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

Hypercholesterolemia impairs endothelial function. However, the critical level of serurn total cholesterol at which endothelial dysfunction Occurs is unknown at present. We investigated cross-sectionally the correlation between urinary excretion of cyclic guanosine 3',5' monophosphate (cGMP), a second messenger of nitric oxide (NO) and serum total cholesterol concentrations in a general population sample of Japanese men and women. The samples comprised 1541 subjects (788 men and 753 women) aged 40-79 years, who participated in cardiovascular risk surveys between 1997 and 2002 and underwent a 24 h urine collection. Urinary excretion of cGMP was measured using a I-125-labeled cGMP radioimmunoassay and was adjusted for urinary creatinine excretion (nmol/mmol creatinine). The mean urinary cGMP excretion correlated linearly and inversely with serum total cholesterol level: mean cGMP excretion adjusted for age, sex and cardiovascular risk factors was 61.7, 53.6, 50.8. 49.2. 47.3 and 46.4 nmol/mmol for total cholesterol levels < 4.14, 4.14-4.64, 4.65-5.16, 5.17-5.68, 5.69-6.20 and >= 6.21 mmol/L, respectively (p = 0.007). This relation was more evident among individuals with end-organ damage, among subjects with higher C-reactive protein (CRP) levels and among postmenopausal women. Our data suggest a reduction of NO bioactivity with higher serum total cholesterol levels, even within clinically normal cholesterol levels. (c) 2004 Elsevier Ireland Ltd. All rights reserved.