%0 Journal Article %J Circulation %D 2003 %T Interaction between soluble thrombomodulin and intercellular adhesion molecule-1 in predicting risk of coronary heart disease. %A Wu, Kenneth K %A Aleksic, Nena %A Ballantyne, Christie M %A Ahn, Chul %A Juneja, Harinder %A Eric Boerwinkle %K Case-Control Studies %K Coronary Disease %K Female %K Humans %K Intercellular Adhesion Molecule-1 %K Male %K Middle Aged %K Proportional Hazards Models %K Risk Factors %K Thrombomodulin %X

BACKGROUND: Results from previous ARIC (Atherosclerosis Risk In Communities) analyses indicate that soluble intercellular adhesive molecule-1 (sICAM) and soluble thrombomodulin (sTM) levels are associated with risk of coronary heart disease (CHD) in an opposite direction. A high sICAM level increases the risk of CHD, whereas a high level of sTM has a lower risk of CHD. It was unclear whether there was an interaction between sTM and sICAM.

METHODS AND RESULTS: Using a nested case-cohort design, we measured sTM and sICAM in 317 incident CHD cases and 726 non-cases from the ARIC participants. Consistent with our previous reports, sICAM values in the upper versus the lower tertile increased the risk of CHD event by approximately 2-fold (95% confidence interval [CI], 1.46 to 2.87) whereas sTM values in the lower versus the upper tertile increased CHD risk by approximately 4-fold (95% CI, 2.80 to 5.74). Interaction between these 2 parameters was determined by weighted Cox proportional hazard regression. A significant interaction (P=0.038) was noted. Combinatorial analysis shows a significant increase in CHD risk ratio (RR) (4.66, 95% CI, 1.89 to 11.46) of the lower sTM/upper sICAM group versus the upper sTM/lower sICAM group. Individuals whose sTM values were in the upper tertile had a RR below 1, even when sICAM were in the upper tertile. The RR of lower tertile sTM was increased by sICAM in a tertile-dependent manner.

CONCLUSIONS: Weighted Cox proportional hazard analysis shows a significant interaction between sTM and sICAM in predicting risk of CHD event. Combinatorial analysis reveals that an upper tertile sICAM had a significant increase in the risk of a CHD event only when sTM was in the lower tertile.

%B Circulation %V 107 %P 1729-32 %8 2003 Apr 08 %G eng %N 13 %1 https://www.ncbi.nlm.nih.gov/pubmed/12668515?dopt=Abstract %R 10.1161/01.CIR.0000064894.97094.4F