Association of sICAM-1 and MCP-1 with coronary artery calcification in families enriched for coronary heart disease or hypertension: the NHLBI Family Heart Study.
BACKGROUND
Data accumulated from mouse studies and in vitro studies of human arteries support the notion that soluble intercellular adhesion molecule-1 (sICAM-1) and monocyte chemoattractant protein-1 (MCP-1) play important roles in the inflammation process involved in atherosclerosis. However, at the population level, the utility of sICAM-1 and MCP-1 as biomarkers for subclinical atherosclerosis is less clear. In the follow-up exam of the NHLBI Family Heart Study, we evaluated whether plasma levels of sICAM-1 and MCP-1 were associated with coronary artery calcification (CAC), a measure of the burden of coronary atherosclerosis.


METHODS
CAC was measured using the Agatston score with multidetector computed tomography. Information on CAC and MCP-1 was obtained in 2246 whites and 470 African Americans (mean age 55 years) without a history of coronary heart disease (CHD). Information on sICAM-1 was obtained for white participants only.


RESULTS
In whites, after adjustment for age and gender, the odds ratios (ORs) of CAC (CAC > 0) associated with the second, third, fourth, and fifth quintiles of sICAM-1 compared to the first quintile were 1.22 (95% confidence interval [CI]: 0.91-1.63), 1.15 (0.84-1.58), 1.49 (1.09-2.05), and 1.72 (1.26-2.36) (p = 0.0005 for trend test), respectively. The corresponding ORs for the second to fifth quintiles of MCP-1 were 1.26 (0.92-1.73), 0.99 (0.73-1.34), 1.42 (1.03-1.96), and 2.00 (1.43-2.79) (p < 0.0001 for trend test), respectively. In multivariable analysis that additionally adjusted for other CHD risk factors, the association of CAC with sICAM-1 and MCP-1 was attenuated and no longer statistically significant. In African Americans, the age and gender-adjusted ORs of CAC associated with the second and third tertiles of MCP-1 compared to the first tertile were 1.16 (0.64-2.08) and 1.25 (0.70-2.23) (p = 0.44 for trend test), respectively. This result did not change materially after additional adjustment for other CHD risk factors. Test of race interaction showed that the magnitude of association between MCP-1 and CAC did not differ significantly between African Americans and whites. Similar results were obtained when CAC > or = 10 was analyzed as an outcome for both MCP-1 and sICAM-1.


CONCLUSIONS
This study suggests that sICAM-1 and MCP-1 are biomarkers of coronary atherosclerotic burden and their association with CAC was mainly driven by established CHD risk factors.
Tang
Weihong
W
Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA. tang0097@umn.edu
Pankow
James S
JS
Carr
J Jeffrey
JJ
Tracy
Russell P
RP
Bielinski
Suzette J
SJ
North
Kari E
KE
Hopkins
Paul N
PN
Kraja
Aldi T
AT
Arnett
Donna K
DK
D015415:Biomarkers / Q000097:blood; D002114:Calcinosis / Q000097:blood*; D018932:Chemokine CCL2 / Q000097:blood*; D003324:Coronary Artery Disease / Q000097:blood*; D003331:Coronary Vessels / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000097:blood; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D014057:Tomography, X-Ray Computed
D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D018799:Intercellular Adhesion Molecule-1