Kaysen George A, Levin Nathan W, Mitch William E, Chapman Anna L P, Kubala Lukas, Eiserich Jason P
Department of Internal Medicine, Division of Nephrology, University of California, and Department of Biochemistry and Molecular Medicine, Davis, CA, USA.
Blood Purif. 2006;24(5-6):508-16. doi: 10.1159/000096471. Epub 2006 Oct 23.
BACKGROUND/AIMS: In otherwise healthy adults, high C-reactive protein (CRP) levels are associated with cardiovascular disease and have been linked to an inflammatory state. The presence of vascular disease is also associated with increased expression of adhesion molecules, including soluble intercellular adhesion molecule (sICAM), vascular endothelial growth factor (VEGF) and leukocyte-derived myeloperoxidase (MPO). These associations suggest potential mechanisms whereby inflammation may injure the vascular endothelium, but the recognition of how these mediators act in concert remain poorly characterized. That the prevalence of atherosclerosis and markers of inflammation are increased in renal failure patients suggests that inflammation causes accelerated vascular disease.
In hemodialysis patients, we examined the relationships between plasma CRP and sICAM, VEGF and MPO longitudinally. We determined whether episodes of a high CRP value were paralleled by simultaneous increases in mediators of inflammatory injury or molecules associated with endothelial cell adhesion or growth and whether CRP levels correlated with those of VEGF and MPO.
Episodic increases in CRP were accompanied by higher levels of VEGF, sICAM and MPO. However, there was no correlation between serum CRP levels or other acute phase proteins and either MPO or VEGF, nor was there a constant temporal relationship between MPO and CRP. By contrast, MPO and VEGF levels were closely correlated with one another during episodes of inflammation (p = 0.0001), and CRP and interleukin-6 levels were also correlated. Increases in MPO tended to be restricted to patients with grafts or catheters, and not those with AV fistulas.
These results suggest that high plasma levels of CRP or other acute phase proteins in cross-sectional studies should be interpreted cautiously when defining mechanisms underlying cardiovascular disease in the hemodialysis patient population. One, or more than one inflammatory repertoire may be activated, one involving hepatic acute phase proteins and the other neutrophil activation and each may contribute separately to outcomes. Better prognostic information may be obtained by measurement of more markers than CRP alone, such as MPO and VEGF.
背景/目的：在其他方面健康的成年人中，高C反应蛋白（CRP）水平与心血管疾病相关，并与炎症状态有关。血管疾病的存在也与黏附分子表达增加有关，包括可溶性细胞间黏附分子（sICAM）、血管内皮生长因子（VEGF）和白细胞衍生的髓过氧化物酶（MPO）。这些关联提示了炎症可能损伤血管内皮的潜在机制，但对于这些介质如何协同作用的认识仍不充分。肾衰竭患者中动脉粥样硬化患病率和炎症标志物增加，提示炎症会导致血管疾病加速发展。
在血液透析患者中，我们纵向研究了血浆CRP与sICAM、VEGF和MPO之间的关系。我们确定CRP值升高的发作是否与炎症损伤介质或与内皮细胞黏附或生长相关分子的同时增加平行，以及CRP水平是否与VEGF和MPO水平相关。
CRP的间歇性升高伴随着VEGF、sICAM和MPO水平升高。然而，血清CRP水平或其他急性期蛋白与MPO或VEGF之间均无相关性，MPO与CRP之间也没有恒定的时间关系。相比之下，在炎症发作期间，MPO和VEGF水平彼此密切相关（p = 0.0001），CRP和白细胞介素-6水平也相关。MPO升高往往局限于有移植物或导管的患者，而非动静脉内瘘患者。
这些结果表明，在横断面研究中，当确定血液透析患者群体中心血管疾病的潜在机制时，应谨慎解释高血浆CRP水平或其他急性期蛋白。一种或多种炎症反应可能被激活，一种涉及肝脏急性期蛋白，另一种涉及中性粒细胞激活，每种可能分别对结果产生影响。通过检测比单独的CRP更多的标志物，如MPO和VEGF，可能获得更好的预后信息。
