April 8, 2003Open Access
View Full PaperInteraction Between Soluble Thrombomodulin and Intercellular Adhesion Molecule-1 in Predicting Risk of Coronary Heart Disease
Key Result
The combination of lower tertile sTM and upper tertile sICAM significantly increased the risk of a CHD event compared to upper sTM and lower sICAM (RR 4.66; 95% CI 1.89-11.46; P=0.038 for interaction).
Study Design
Type
Cohort (n=1,043)
Multicenter
Yes
Structured PICO
Does the interaction between soluble thrombomodulin and intercellular adhesion molecule-1 predict the risk of coronary heart disease?
P
Population
1,043 ARIC participants (317 incident CHD cases and 726 non-cases) evaluated for the interaction between sTM and sICAM in predicting CHD risk.
E
Exposure
Soluble thrombomodulin (sTM) and soluble intercellular adhesive molecule-1 (sICAM) levels (evaluated by tertiles)
C
Comparator
Different tertiles of sTM and sICAM
O
Outcome
Incident coronary heart disease (CHD) eventshard clinical
An upper tertile of sICAM significantly increases the risk of a CHD event only when sTM is in the lower tertile, demonstrating a significant interaction between these biomarkers in predicting CHD risk.
Main Result
Relative Risk: 4.66 (95% CI 1.89–11.46)
p-value: p=0.038 for interaction
Abstract
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.