Association of Lipopolysaccharide-Binding
Protein and Coronary Artery Disease in Men
Philipp M. Lepper, MD,*† Christian Schumann, MD,† Kathy Triantaﬁlou, P
F. Maximilian Rasche, MD,† Tibor Schuster, MS,§ Hedwig Frank,† E. Marion Schneider, P
Martha Triantaﬁlou, P
D,‡ Maximilian von Eynatten, MD#
Bern, Switzerland; Ulm and Munich, Germany; and Brighton, United Kingdom
In this study we tested the hypothesis that lipopolysaccharide-binding protein (LBP) might be able to be used as
a biomarker for coronary artery disease (CAD).
The mechanisms by which the innate immune recognition of pathogens could lead to atherosclerosis remain
unclear. Lipopolysaccharide-binding protein is the ﬁrst protein to encounter lipopolysaccharide and to deliver it
to its cellular targets, toll-like receptors; therefore, its presence might be a reliable biomarker that indicates acti-
vation of innate immune responses.
A total of 247 men undergoing elective coronary angiography were studied, and the extent of coronary athero-
sclerosis was assessed by 2 established scores: “extent score” and “severity score.” Levels of LBP, markers of
inﬂammation, and traditional risk factors for CAD were assessed.
Serum LBP concentration was signiﬁcantly increased in 172 patients with angiographically conﬁrmed CAD com-
pared with 75 individuals without coronary atherosclerosis (20.6 Ϯ 8.7 pg/ml vs. 17.1 Ϯ 6.0 pg/ml, respectively;
p ϭ 0.002). Moreover in multivariable logistic regression analyses, adjusted for established cardiovascular risk
factors and markers of systemic inﬂammation, LBP was a signiﬁcant and independent predictor of prevalent
CAD (p Ͻ 0.05 in all models).
Lipopolysaccharide-binding protein might serve as a novel marker for CAD in men. The present results underlie
the potential importance of innate immune mechanisms for CAD. Further studies are warranted to bolster the
data and to identify pathogenetic links between innate immune system activation and atherosclerosis. (J Am
Coll Cardiol 2007;50:25–31) © 2007 by the American College of Cardiology Foundation
Atherosclerosis can be regarded as a chronic inﬂammatory
response limited to the vascular bed (1). New insights into
the pathogenesis of atherosclerosis clearly indicate that
multiple factors, such as hypertension, high plasma concen-
trations of low-density lipoprotein (LDL) cholesterol, dia-
betes mellitus, and infection, inﬂuence the development and
progression of atherosclerosis (2).
Although the inﬂammatory nature of the disease is widely
accepted, what initiates and maintains this inﬂammatory
state remains unclear. Microbial infections seem to promote
myocardial infarction (3). Epidemiologic evidence has sug-
gested a link between microbial infection and atherosclerosis
(4–6). In particular, it is possible that lipopolysaccharide
(LPS) from bacteria such as Chlamydia pneumonia (7–9),
Helicobacter pylori (10,11), or Porphyromonas gingivalis
(6,12) may be triggering the inﬂammatory response that
leads to atherogenesis. The question that remains is how
these microbial pathogens trigger this inﬂammatory disease.
The recent discovery of toll-like receptors (TLRs), which
are the key microbial sensors of the innate immune system
(13), in atherosclerotic lesions (14) provides a mechanistic
link between infection, innate immune recognition, inﬂam-
mation, and atherosclerosis.
The detection of microbial infection and the initiation of
the innate immune response rely on TLRs, which recognize
microbial “signatures.” Ligation of TLRs results in the
recruitment of an adaptor protein, myeloid differentiation
factor 88 (MyD88), which ﬁnally leads to activation of
B and the production of proinﬂammatory
cytokines. A link between TLRs and atherosclerosis has
been suggested in studies where expression of TLR-1, -2,
From the *Department of Intensive Care Medicine, University Hospital of Bern
(Inselspital), Bern, Switzerland; †Department of Internal Medicine II, University of
Ulm, Ulm, Germany; ‡Infection and Immunity Group, University of Sussex,
Brighton, United Kingdom; §Institute of Medical Statistics and Epidemiology,
Technical University of Munich, Munich, Germany; ʈSection of Experimental
Anaesthesiology, University of Ulm, Ulm, Germany; and the #Department of
Nephrology, Technical University of Munich, Munich, Germany. The ﬁrst three
authors contributed equally to this work.
Manuscript received November 27, 2006; revised manuscript received January 11,
2007, accepted February 5, 2007.
Journal of the American College of Cardiology Vol. 50, No. 1, 2007
© 2007 by the American College of Cardiology Foundation ISSN 0735-1097/07/$32.00
Published by Elsevier Inc. doi:10.1016/j.jacc.2007.02.070