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© American Heart Association, Inc.

Clinical Investigation and Reports

Interaction Between Soluble Thrombomodulin and Intercellular Adhesion Molecule-1 in Predicting Risk of Coronary Heart Disease

From the Vascular Biology Research Center and Department of Internal Medicine (K.K.W., N.A., C.A., H.J.), Human Genetics Center (E.B.) University of Texas-Houston Health Science Center, and Department of Medicine, Baylor College of Medicine (C.M.B.), Houston, Tex.

Guest editor for this article was Paul M Ridker, MD, Brigham and Women’s Hospital, Harvard University, Boston, Mass.Correspondence to Kenneth K. Wu, MD, PhD, Division of Hematology, University of Texas-Houston Medical School, 6431 Fannin St, MSB 5.016, Houston, TX 77030. E-mail Kenneth.K.Wu{at}uth.tmc.edu

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 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 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.

Conclusion— 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.

Key Words: glycoproteins • cell adhesion molecules • coronary disease • risk factors

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