Seiler Sarah, Schlitt Axel, Jiang Xian-Cheng, Ulrich Christof, Blankenberg Stefan, Lackner Karl J, Girndt Matthias, Werdan Karl, Buerke Michael, Fliser Danilo, Heine Gunnar H
Department of Medicine IV, Saarland University, Homburg/Saar, Germany.
Nephrol Dial Transplant. 2008 Nov;23(11):3599-604. doi: 10.1093/ndt/gfn296. Epub 2008 May 25.
Patients with chronic kidney disease (CKD) have an increased risk for cardiovascular events (CVE). Uraemic dyslipidaemia, which is characterized by low HDL-cholesterol (HDL-C) and elevated triglycerides' levels, may contribute to this elevated cardiovascular risk. Cholesteryl ester transfer protein (CETP) lowers HDL-C by transferring cholesterol esters to LDL and VLDL particles. We tested the hypothesis that CETP activity is associated with CVE in patients with CKD stage V.
We measured CETP activity and cholesterol levels in 69 haemodialysis patients. CVE and death were prospectively assessed over a follow-up period of 48 months.
CETP activity was negatively correlated with HDL-C levels in patients without lipid-lowering medication (r = -0.379, P = 0.005). We found no difference in CETP activity in patients with cardiovascular disease at baseline compared to patients without cardiovascular disease. The same was true for incident CVE during the follow-up. When stratifying patients by median CETP activity, patients with high CETP activity did not have an increased risk for CVE (P = 0.901 by the log-rank test) or death (P = 0.615). Similarly, after stratifying patients by median HDL-C no increased risk for CVE (P = 0.780) or death (P = 0.838) was found in patients with low HDL-C.
In summary, although CETP activity correlated with HDL-C levels, neither high CETP activity nor low HDL-C was associated with CVE in CKD stage V patients. Thus, pharmacological modification of HDL-C by CETP inhibitors seems to be of questionable value in these patients.
慢性肾脏病（CKD）患者发生心血管事件（CVE）的风险增加。以高密度脂蛋白胆固醇（HDL-C）降低和甘油三酯水平升高为特征的尿毒症血脂异常可能导致心血管风险升高。胆固醇酯转运蛋白（CETP）通过将胆固醇酯转移至低密度脂蛋白（LDL）和极低密度脂蛋白（VLDL）颗粒而降低HDL-C。我们检验了CKD 5期患者中CETP活性与CVE相关的假设。
我们测定了69例血液透析患者的CETP活性和胆固醇水平。在48个月的随访期内对CVE和死亡情况进行前瞻性评估。
在未服用降脂药物的患者中，CETP活性与HDL-C水平呈负相关（r = -0.379，P = 0.005）。我们发现，基线时患有心血管疾病的患者与未患心血管疾病的患者相比，CETP活性没有差异。随访期间发生的CVE情况也是如此。按照CETP活性中位数对患者进行分层时，CETP活性高的患者发生CVE的风险未增加（对数秩检验P = 0.901）或死亡风险未增加（P = 0.615）。同样，按照HDL-C中位数对患者进行分层后，HDL-C低的患者发生CVE的风险（P = 0.780）或死亡风险（P = 0.838）未增加。
总之，尽管CETP活性与HDL-C水平相关，但在CKD 5期患者中，CETP活性高和HDL-C低均与CVE无关。因此，在这些患者中，使用CETP抑制剂对HDL-C进行药物调节似乎价值存疑。
