Association of n-3 polyunsaturated fatty acids with soluble thrombomodulin as a marker of endothelial damage: A cross-sectional pilot study

BackgroundSoluble thrombomodulin (sTM) is a useful marker of vascular endothelial damage. Although n-3 polyunsaturated fatty acids (n-3 PUFAs) (eicosapentaenoic acid: EPA; docosahexaenoic acid: DHA) have various cardiovascular protective effects, their effect in preventing vascular endothelial damage remains unclear. Furthermore, little is known about the association of EPA and DHA with sTM using the cross-sectional study method.Methods and resultsThis pilot study was designed as a hospital-based cross-sectional study to investigate the relationships between serum n-3 PUFA levels and sTM level in patients with the presence of one or more risk factors for atherosclerosis. Of the 534 sequential patients who had routinely been registered to a study cohort of our institute, 324 patients without chronic kidney disease (because sTM is eliminated by renal excretion and the serum sTM level is increased by renal dysfunction) were enrolled in this study. In a multivariate analysis after adjustment for atherosclerotic risk factors, elevated EPA + DHA level was an independent variable of decreased sTM level (β = −0.183, p = 0.0006). The serum levels of EPA and DHA showed a strong correlation (r = 0.736, p < 0.0001); however, multivariate analysis including EPA and DHA revealed that serum DHA (β = −0.243, p = 0.003), but not serum EPA (β = 0.049, p = 0.538), was identified as an independent negative determinant of sTM level.ConclusionAlthough there are numerous unresolved issues in regard to the differences in the cardiovascular protective effects between EPA and DHA, DHA may be associated with a decrease in sTM. A large-scale trial would be warranted to demonstrate whether the beneficial effect of n3-PUFAs therapy on endothelial damage and improvement of endothelial function might also result in fewer clinical cardiovascular events.