Zimmermann J, Herrlinger S, Pruy A, Metzger T, Wanner C
Department of Medicine, University Clinic Würzburg, Germany.
Kidney Int. 1999 Feb;55(2):648-58. doi: 10.1046/j.1523-1755.1999.00273.x.
Atherosclerosis, a major problem in patients on chronic hemodialysis, has been characterized as an inflammatory disease. C-reactive protein (CRP), the prototypical acute phase protein in humans, is a predictor of cardiovascular mortality in the general population. We hypothesize that several of the classic, as well as nontraditional, cardiovascular risk factors may respond to acute phase reactions. An activated acute phase response may influence or predict cardiovascular risk.
In 280 stable hemodialysis patients, serum lipids, apolipoproteins (apo) A-I and B, lipoprotein(a) [Lp(a)], fibrinogen, and serum albumin (Salb) were determined in relation to CRP and serum amyloid A (SAA), two sensitive markers of an acute phase response. Mortality was monitored prospectively over a two year period.
Serum CRP and SAA were found to be elevated (more than 8 and more than 10 mg/liter, respectively) in 46% and 47% of the patients in the absence of clinically apparent infection. Patients with elevated CRP or SAA had significantly higher serum levels of Lp(a), higher plasma fibrinogen, and lower serum levels of high-density lipoprotein cholesterol, apo A-I, and Salb than patients with normal CRP or SAA. The rise in Lp(a) concentration was restricted to patients exhibiting high molecular weight apo(a) isoforms. During follow-up, 72 patients (25.7%) had died, mostly due to cardiovascular events (58%). Overall mortality and cardiovascular mortality were significantly higher in patients with elevated CRP (31% vs. 16%, P < 0.0001, and 23% vs. 5%, P < 0.0001, respectively) or SAA (29% vs. 19%, P = 0.004, and 20 vs. 10%, P = 0.008, respectively) and were also higher in patients with Salb of lower than 40 g/liter (44% vs. 14%, P < 0.0001, and 34% vs. 6%, P < 0.0001, respectively). Univariate Cox regression analysis demonstrated that age, diabetes, pre-existing cardiovascular disease, body mass index, CRP, SAA, Salb, fibrinogen, apo A-I, and Lp(a) were significantly associated with the risk of all-cause and cardiovascular mortality. During multivariate regression analysis, SAA, fibrinogen, apo A-I, and Lp(a) lost their predictive values, but age and CRP remained powerful independent predictors of both overall death and cardiovascular death.
These results suggest that a considerable number of hemodialysis patients exhibit an activated acute phase response, which is closely related to high levels of atherogenic vascular risk factors and cardiovascular death. The mechanisms of activated acute phase reaction in patients on chronic hemodialysis remain to be identified. A successful treatment of the inflammatory condition may improve long-term survival in these patients.
动脉粥样硬化是慢性血液透析患者的一个主要问题，其被认为是一种炎症性疾病。C反应蛋白（CRP）是人类典型的急性期蛋白，是普通人群心血管死亡率的一个预测指标。我们推测一些经典的以及非传统的心血管危险因素可能会对急性期反应产生响应。激活的急性期反应可能会影响或预测心血管风险。
在280例稳定的血液透析患者中，测定了血清脂质、载脂蛋白（apo）A-I和B、脂蛋白(a)[Lp(a)]、纤维蛋白原以及血清白蛋白（Salb）与CRP和血清淀粉样蛋白A（SAA）的关系，CRP和SAA是急性期反应的两个敏感标志物。对患者进行了为期两年的前瞻性死亡监测。
在无临床明显感染的情况下，分别有46%和47%的患者血清CRP和SAA升高（分别超过8mg/L和10mg/L）。与CRP或SAA正常的患者相比，CRP或SAA升高的患者血清Lp(a)水平显著更高、血浆纤维蛋白原水平更高，而高密度脂蛋白胆固醇、apo A-I和Salb的血清水平更低。Lp(a)浓度的升高仅限于表现出高分子量apo(a)异构体的患者。在随访期间，72例患者（25.7%）死亡，主要死于心血管事件（58%）。CRP升高（分别为31%对16%，P<0.0001；23%对5%，P<0.0001）或SAA升高（分别为29%对19%，P=0.004；20%对10%，P=0.008）的患者总体死亡率和心血管死亡率显著更高，血清白蛋白低于40g/L的患者总体死亡率和心血管死亡率也更高（分别为44%对14%，P<0.0001；34%对6%，P<0.0001）。单因素Cox回归分析表明，年龄、糖尿病、既往心血管疾病、体重指数、CRP、SAA、Salb、纤维蛋白原、apo A-I和Lp(a)与全因死亡和心血管死亡风险显著相关。在多因素回归分析中，SAA、纤维蛋白原、apo A-I和Lp(a)失去了其预测价值，但年龄和CRP仍然是总体死亡和心血管死亡的有力独立预测因素。
这些结果表明，相当数量的血液透析患者表现出激活的急性期反应，这与高水平的致动脉粥样硬化血管危险因素和心血管死亡密切相关。慢性血液透析患者激活急性期反应的机制仍有待确定。成功治疗炎症状态可能会改善这些患者的长期生存率。
