Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:972-978
© 1999 American Heart Association, Inc.
Original Contributions |
C-Reactive Protein in Healthy Subjects: Associations With Obesity, Insulin Resistance, and Endothelial Dysfunction
A Potential Role for Cytokines Originating From Adipose Tissue?
From the Centre for Diabetes and Cardiovascular Risk, Department of Medicine, University College London Medical School, G Block, Archway Wing, Whittington Hospital, Archway Road, London N19 3UA, UK (J.S.Y., S.W.C.); the Department of Medicine, Academic Hospital Vrije Universiteit and the Institute for Cardiovascular Research Vrije Universiteit, 1081 HV Amsterdam, Netherlands (C.D.A.S.); and the Gaubius Laboratory, TNO-PG, 2301 CE Leiden, Netherlands (J.J.E.).
Correspondence to Professor John S. Yudkin, Centre for Diabetes and Cardiovascular Risk, Department of Medicine, University College London Medical School, G Block, Archway Wing, Whittington Hospital, Archway Road, London N19 3UA, UK. E-mail j.yudkin{at}ucl.ac.uk
Abstract—C-reactive protein, a
hepatic acute phase protein largely regulated by circulating levels of
interleukin-6, predicts coronary heart disease incidence in
healthy subjects. We have shown that subcutaneous adipose tissue
secretes interleukin-6 in vivo. In this study we have sought
associations of levels of C-reactive protein and interleukin-6 with
measures of obesity and of chronic infection as their putative
determinants. We have also related levels of C-reactive protein and
interleukin-6 to markers of the insulin resistance syndrome and of
endothelial dysfunction. We performed a cross-sectional
study in 107 nondiabetic subjects: (1) Levels of C-reactive protein,
and concentrations of the proinflammatory cytokines
interleukin-6 and tumor necrosis factor-
, were related to all
measures of obesity, but titers of antibodies to Helicobacter
pylori were only weakly and those of Chlamydia
pneumoniae and cytomegalovirus were not significantly
correlated with levels of these molecules. Levels of C-reactive protein
were significantly related to those of interleukin-6
(r=0.37, P<0.0005) and tumor necrosis
factor- (r=0.46, P<0.0001). (2)
Concentrations of C-reactive protein were related to insulin resistance
as calculated from the homoeostasis model assessment model, blood
pressure, HDL, and triglyceride, and to markers of
endothelial dysfunction (plasma levels of von
Willebrand factor, tissue plasminogen
activator, and cellular fibronectin). A mean standard
deviation score of levels of acute phase markers correlated closely
with a similar score of insulin resistance syndrome variables
(r=0.59, P<0.00005), this relationship
being weakened only marginally by removing measures of obesity from the
insulin resistance score (r=0.53,
P<0.00005). These data suggest that adipose tissue is
an important determinant of a low level, chronic inflammatory state as
reflected by levels of interleukin-6, tumor necrosis factor-, and
C-reactive protein, and that infection with H
pylori, C pneumoniae, and
cytomegalovirus is not. Moreover, our data support the concept that
such a low-level, chronic inflammatory state may induce insulin
resistance and endothelial dysfunction and thus link
the latter phenomena with obesity and cardiovascular disease.
Key Words: C-reactive protein • insulin resistance • obesity • endothelial dysfunction • interleukin-6
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