Kawauchi Kenji, Tani Shigemasa, Nagao Ken, Hirayama Atsushi
Department of Cardiology, Surugadai Nihon University Hospital, Tokyo, Japan; Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
Department of Cardiology, Surugadai Nihon University Hospital, Tokyo, Japan; Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
J Cardiol. 2014 Oct;64(4):312-7. doi: 10.1016/j.jjcc.2014.02.004. Epub 2014 Mar 26.
Soluble 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.
This 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.
Although 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.
可溶性血栓调节蛋白（sTM）是血管内皮损伤的一个有用标志物。尽管n-3多不饱和脂肪酸（n-3 PUFAs，二十碳五烯酸：EPA；二十二碳六烯酸：DHA）具有多种心血管保护作用，但其在预防血管内皮损伤方面的作用仍不明确。此外，利用横断面研究方法对EPA和DHA与sTM之间的关联了解甚少。
本初步研究设计为一项基于医院的横断面研究，旨在调查存在一种或多种动脉粥样硬化危险因素的患者血清n-3 PUFA水平与sTM水平之间的关系。在我们研究所的一个研究队列中常规登记的534例连续患者中，324例无慢性肾脏病的患者（因为sTM通过肾脏排泄清除，且血清sTM水平因肾功能不全而升高）被纳入本研究。在对动脉粥样硬化危险因素进行校正后的多变量分析中，EPA+DHA水平升高是sTM水平降低的一个独立变量（β=-0.183，p=0.0006）。EPA和DHA的血清水平显示出很强的相关性（r=0.736，p<0.0001）；然而，包括EPA和DHA的多变量分析显示，血清DHA（β=-0.243，p=0.003）而非血清EPA（β=0.049，p=0.538）被确定为sTM水平的一个独立负性决定因素。
尽管关于EPA和DHA在心血管保护作用方面的差异存在许多未解决的问题，但DHA可能与sTM降低有关。有必要进行大规模试验以证明n-3 PUFAs治疗对内皮损伤的有益作用及内皮功能的改善是否也会导致临床心血管事件减少。
