Cardiovascular Journal of Africa: Vol 26 No 1 (January/February 2015)

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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 26, No 1, January/February 2015 AFRICA 23
Whether soluble adhesion molecules are increased in
subclinical cardiovascular disease has been investigated in
several studies. In a sample from the Monitoring Trends in
and Determinants in Cardiovascular Disease (MONICA) trial,
despite sICAM-1 levels being independently associated with
the risk of having at least one carotid or femoral plaque, no
significant association was found with carotid intima–media
thickness (CIMT).16 Similarly, Amar et al. showed interleukin-6
and ICAM levels were associated with stable atherosclerotic
plaque but not with IMT.17
In a prospective study by Gross et al., higher sICAM1 levels
were associated significantly and in a graded fashion with
common CIMT in participants with advanced plaque.18 The
study indicated an early (mean age 40 years) involvement of
sCAM1 in the development of atherosclerosis, independent of
traditional cardiovascular risk factors and CRP levels. Moreover,
no association was found in patients with low total burden of
atherosclerosis.
Our results are in alignment with these studies. In consecutive
patients referred for echocardiographic examination, we found
no association between adhesion molecules and aortic stiffness,
which is a predictor of cardiovascular disease.
Despite all these studies, the role of soluble adhesion
molecules in cardiovascular disease has not been fully established
and clinical studies show inconsistent results. There are some
possible explanations for this inconsistency. First, vascular
endothelial and smooth muscle cells express VCAM-1, while
ICAM-1 expression is not limited to these cells and is expressed
in many cells, including haematopoietic cells and fibroblasts.3
Therefore, VCAM-1 may be a marker of plaque burden or
activity, whereas ICAM-1 may be a marker of low-grade
inflammation. Some authors have suggested that ICAM-1 is
predictive in initially healthy people and VCAM-1 in patients
with atherosclerosis.3
Second, levels of soluble adhesion molecules are influenced by
age, smoking status, diabetes and other inflammatory conditions,
and even with exercise or changes in arterial pressure.19,20
Moreover, there is a lack of knowledge of which cellular and
molecular factors determine the levels of adhesion molecules,
since VCAM and ICAM, like other inflammatory molecules,
may have regulations at many levels.6
Aortic stiffness is an independent predictor of cardiovascular
risk. Arterial stiffening is a physiological aspect of ageing
and is the result of the joint effects of adhesion molecules,
integrins, metalloproteinases, the renin–angiotension system,
and inflammation of cellular components (endothelium,
vascular smooth muscle, fibroblasts and matrix components) on
the structural and functional properties of the artery.21 Indeed,
recent studies have shown the importance of inflammation in
arterial stiffening. Increased levels of inflammatory markers
have been associated with arterial stiffness in various groups,
including healthy subjects, hypertensives, and community-based
groups.21-25
In the study of Bussel et al., biomarkers of endothelial
dysfunction and low-grade inflammation, including adhesion
molecules, were associated with greater arterial stiffness
over a six-year period.26 A causative effect of acute systemic
inflammation on increasing large-artery stiffness and decrease
in wave reflections was also shown in patients receiving
vaccinations.27
Several mechanisms may explain the link between arterial
stiffness and inflammation. First, degradation of the elastin
and collagen of the vessel wall may be increased by activation
of matrix metalloproteinases, which may be mediated by
increased levels of inflammatory mediators, including adhesion
molecules.11 Inflammation may also provoke fibrosis and smooth
muscle proliferation, which would subsequently cause arterial
stiffness.11
Another possible explanation is the major role of the
endothelium in arterial stiffness. Inflammation causes endothelial
dysfunction and alters arterial distensibility by impairing the
production of vasodilatory factors.27 One last, speculative
explanation could be arterial stiffness causing inflammation,
since elevated pulse pressure and increased shear stress may
stimulate inflammation and increase the expression of adhesion
molecules.20,22,28
Conclusion
We were unable to find a significant correlation between aortic
stiffness and circulating adhesion molecules (VCAM-1 and
ICAM-1). Possible causes of this finding have been discussed
above. However, other factors may have affected the results.
The mean age in our study was 55.6 ± 10.5 years. Since arterial
stiffening typically occurs after the age of 60 years, our study
population represented a relatively young population.26 Second,
arterial stiffening is not a uniform condition in all arterial
systems, and aortic distensibility is a local measure of arterial
stiffness.22 Third, levels of adhesion molecules were measured
only once, and they may be subject to intra-individual variability.
The small study size is another limitation of this study.
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