Soluble thrombomodulin and coronary heart disease.

Abstract

Endothelial thrombomodulin is a major vasoprotective molecule. The membrane thrombomodulin is digested by proteases and the degradation products are detectable in circulating blood. The purpose of this review is to provide recent information regarding the relationship of soluble thrombomodulin with coronary heart disease. Results from a population-based, prospective, coronary heart disease, case-cohort study reveal an inverse relationship between plasma soluble thrombomodulin and the relative risk of coronary heart disease. Participants in this study were healthy subjects without acute thrombotic events. They were followed, and coronary heart disease events were ascertained. Individuals with a high level of soluble thrombomodulin are associated with a significant reduction in the relative risk of coronary heart disease events. There is a significant interaction between soluble thrombomodulin and soluble intercellular adhesion molecule-1 in predicting the risk of coronary heart disease events. Individuals with a high soluble thrombomodulin level do not have an increased risk of coronary heart disease, even when soluble intercellular adhesion molecule-1 is at the highest levels. In contrast, at low soluble thrombomodulin levels, soluble intercellular adhesion molecule-1 has a 'dose-dependent' association with coronary heart disease risk. These results suggest an interplay between vasoprotective and pro-inflammatory endothelial molecules. Soluble thrombomodulin and its parent molecule appear to play a predominant role in determinations of the risk of coronary heart disease events. The soluble thrombomodulin level in plasma is an independent risk factor for coronary heart disease. It is inversely associated with coronary heart disease risk. Combinatorial analysis of soluble thrombomodulin and soluble intercellular adhesion molecule-1 provides a more specific assessment of coronary heart disease risk in middle-aged subjects.