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Circulating cell adhesion molecules are correlated with ultrasound-based assessment of carotid atherosclerosis
1Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Insights
Soluble cellular adhesion molecules, including soluble vascular CAM-1 and intercellular adhesion molecule-1, are positively associated with carotid intima-media thickness, indicating a role in atherosclerosis development. These findings suggest systemic inflammation contributes to atherosclerotic lesion progression.
Area of Science:
- Cardiovascular Medicine
- Immunology
- Biochemistry
Background:
- Cellular adhesion molecules (CAMs) are implicated in atherogenesis, but their systemic association with atherosclerosis remains unclear.
- Understanding the role of specific CAMs, such as sVCAM-1 and sICAM-1, is crucial for elucidating atherosclerosis mechanisms.
Purpose of the Study:
- To investigate the association between soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) levels and carotid intima-media thickness (IMT) in outpatients.
- To determine if these associations persist after adjusting for traditional cardiovascular risk factors.
Main Methods:
- Enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of sVCAM-1 and sICAM-1 in 92 outpatients.
- Two-dimensional ultrasound assessed carotid intima-media thickness (IMT) at the common carotid artery and bifurcation.
- Statistical analyses, including correlation and regression, were performed to evaluate associations, with adjustments for age and other risk factors.
Main Results:
- Both sVCAM-1 and sICAM-1 levels showed significant positive correlations with mean and maximal carotid IMT.
- The association between sICAM-1 and carotid IMT remained significant after age adjustment, while the sVCAM-1 association was attenuated.
- Age-adjusted sICAM-1 and sVCAM-1 levels increased progressively with higher IMT tertiles, independent of major cardiovascular risk factors.
Conclusions:
- Serum levels of sVCAM-1 and sICAM-1 are positively associated with carotid intima-media thickness, a marker of early atherosclerosis.
- These findings support the hypothesis that systemic inflammation, as indicated by CAM levels, plays a role in the development and progression of atherosclerotic lesions.
- sICAM-1 demonstrates a robust association with carotid IMT, even after accounting for age and other risk factors.
Abstract:
Although cellular adhesion molecules (CAMs) are hypothesized to play an important role in atherogenesis, the relationship between CAMs and systemic atherosclerosis is uncertain. Among 92 outpatients (48 men; mean+/-SD age, 65+/-9 years), we evaluated the association of soluble vascular CAM-1 (sVCAM-1) and intercellular adhesion molecule-1 (sICAM-1) with carotid intimal-medial thickness (IMT), an index of early atherosclerosis. All subjects underwent a 2-dimensional ultrasound examination of both carotid arteries at the distal common carotid arteries and bifurcation. sVCAM-1 and sICAM-1 levels measured by enzyme-linked immunosorbent assay were significantly correlated with mean IMT of the common carotid artery (r=0.34 and r=0.30, respectively; P<0.01) and carotid bifurcation (r=0.31 and r=0.26, respectively; P<0.05), whereas sVCAM-1 was also positively associated with maximal carotid IMT (r=0.35, P<0.01). Adjustment for age attenuated the association between sVCAM-1 and common (r=0.16, P=0.13) and bifurcation (r=0.18, P=0.07) carotid IMT but had minimal effect on the associations between sICAM-1 and carotid measurements (r=0.32, P<0.01; r=0.23, P<0.05; for common and bifurcation IMT, respectively). Age-adjusted sICAM-1 levels increased in a stepwise fashion across common carotid IMT tertiles (253+/-27 versus 275+/-24 versus 384+/-26 pg/mL for the lowest, intermediate, and highest IMT tertiles, respectively; P<0.01). A similar trend was also found between sVCAM-1 levels and common carotid IMT tertiles (625+/-60 versus 650+/-53 versus 714+/-58 pg/mL; P<0.15). These associations were minimally affected in analyses adjusting for hypertension, diabetes, smoking, low and high density lipoprotein cholesterol, lipoprotein(a), and homocysteine, or in a subgroup analysis limited to those with no prior history of atherothrombotic disease. These data demonstrate a positive association between serum CAMs with carotid IMT and further support the hypothesis that systemic inflammation may have a role in atherosclerotic lesion development.