Becker A, Van Hinsbergh V W, Kostense P J, Jager A, Dekker J M, Nijpels G, Heine R J, Bouter L M, Stehouwer C D
Vrije Universiteit, Amsterdam, The Netherlands; TNO Prevention and Health, Leiden, The Netherlands.
Eur J Clin Invest. 2000 Sep;30(9):763-70. doi: 10.1046/j.1365-2362.2000.00706.x.
Hyperhomocysteinaemia may constitute an independent risk factor for cardiovascular disease, but it is still unclear by which pathophysiological mechanisms homocysteine (tHcy) may promote atherothrombosis. The aim of this study was firstly to examine whether tHcy is associated with endothelial dysfunction, increased adherence of leukocytes, and/or chronic low-grade inflammation, as estimated from plasma levels of von Willebrand factor (vWf), soluble vascular cell adhesion molecule 1 (sVCAM-1) and C-reactive protein (CRP), respectively. Secondly we investigated whether the presence of type 2 diabetes modifies these associations.
Six hundred and ten subjects of a general population of middle-aged and elderly subjects, 170 of whom had type 2 diabetes, participated in this cross-sectional study. Linear regression analyses were used to study whether tHcy was associated with vWf, sVCAM-1 and CRP, and whether the presence of diabetes modified these associations.
After adjustment for confounders, tHcy was significantly but weakly associated with vWf (beta = 0.15, P = 0.05) and sVCAM-1 (beta = 0.082, P = 0.04). tHcy was not significantly associated with CRP (beta = 0.02, P = 0.91). The presence of diabetes did not significantly modify these associations.
This study provides evidence that tHcy is, at most, weakly associated with endothelial dysfunction as estimated from plasma vWf, and with leukocyte adhesion as estimated from plasma sVCAM-1. tHcy was not significantly associated with chronic low-grade inflammation as estimated from plasma CRP. Our data thus suggest that the link between tHcy and atherothrombosis cannot be explained by associations of tHcy with vWf, sVCAM-1 or CRP.
高同型半胱氨酸血症可能是心血管疾病的一个独立危险因素，但同型半胱氨酸（总同型半胱氨酸，tHcy）通过何种病理生理机制促进动脉粥样硬化血栓形成仍不清楚。本研究的目的首先是分别根据血管性血友病因子（vWf）、可溶性血管细胞黏附分子1（sVCAM-1）和C反应蛋白（CRP）的血浆水平，检验tHcy是否与内皮功能障碍、白细胞黏附增加和/或慢性低度炎症相关。其次，我们研究了2型糖尿病的存在是否会改变这些关联。
610名中老年普通人群受试者参与了这项横断面研究，其中170人患有2型糖尿病。采用线性回归分析来研究tHcy是否与vWf、sVCAM-1和CRP相关，以及糖尿病的存在是否会改变这些关联。
在对混杂因素进行调整后，tHcy与vWf（β = 0.15，P = 0.05）和sVCAM-1（β = 0.082，P = 0.04）显著但微弱相关。tHcy与CRP无显著关联（β = 0.02，P = 0.91）。糖尿病的存在并未显著改变这些关联。
本研究提供的证据表明，根据血浆vWf评估，tHcy最多与内皮功能障碍微弱相关；根据血浆sVCAM-1评估，tHcy与白细胞黏附微弱相关。根据血浆CRP评估，tHcy与慢性低度炎症无显著关联。因此，我们的数据表明，tHcy与动脉粥样硬化血栓形成之间的联系无法通过tHcy与vWf、sVCAM-1或CRP的关联来解释。
