Biomarkers of Vascular Calcification and Mortality in Patients with ESRD
Biomarkers of Vascular Calcification and Mortality in Patients with ESRD
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DOI：
10.2215/cjn.05450513
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发表时间：
2014-04-07
影响因子：
9.8
通讯作者：
Parekh, Rulan S.
中科院分区：
文献类型：
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作者：
Scialla, Julia J.;Kao, W. H. Linda;Parekh, Rulan S.
背景血管钙化在接受透析的患者中很常见，并且与死亡率相关。骨保护素 (OPG)、骨桥蛋白 (OPN)、骨形态发生蛋白 7 (BMP-7) 和胎球蛋白 -A 等因素与血管钙化有关。设计、设置、参与者和测量 作为研究的一部分，我们对 1995 年至 1998 年间从美国透析中心招募的 602 名透析患者的血液样本中的 OPG、OPN、BMP-7 和胎球蛋白 -A 进行了测量。 ESRD 研究中健康结果的选择。使用根据人口特征、合并症、血清磷酸盐和钙进行调整的 Cox 比例风险模型评估它们与全因死亡率和心血管死亡率的关联。由于已知糖尿病与血管钙化相关，因此测试了与糖尿病的相互作用。通过训练和验证子队列的嵌套模型中的 C 统计来探索所选生物标志物的预测准确性。结果在长达 13 年的随访（中位数为 3.4 年）内，较高的 OPG 和较低的胎球蛋白 A 水平与较高的死亡率相关。 OPG 最高与最低三分位的调整后风险比 (HR) 为 1.49（95% 置信区间 [95% CI]，1.08 至 2.06），胎球蛋白-A 为 0.69（95% CI，0.52 至 0.92）。在分层模型中，OPG 的最高三分位数与非糖尿病患者的较高死亡率相关（HR，2.42；95% CI，1.35 至 4.34），但与糖尿病患者无关（HR，1.26；95% CI，0.82 至 1.93；交互作用 P = 0.001）。就心血管死亡率而言，较高的胎球蛋白-A 与较低的风险相关（HR，0.85 每 0.1 g/L：95% CI，0.75 至 0.96）。在非糖尿病患者中，较高的 OPG 与较高的风险相关（最高与最低三分位数的 HR 为 2.91；95% CI，1.06 至 7.99），但在糖尿病患者或整体糖尿病患者中则不然。 OPN 和 BMP-7 与总体结果并不独立相关。添加OPG和胎球蛋白-A并没有显着提高死亡率预测的准确性。结论OPG和胎球蛋白-A可能是透析患者全因死亡和心血管死亡的危险因素，但并不能提高风险预测。
BackgroundVascular calcification is common among patients undergoing dialysis and is associated with mortality. Factors such as osteoprotegerin (OPG), osteopontin (OPN), bone morphogenic protein-7 (BMP-7), and fetuin-A are involved in vascular calcification.Design, setting, participants, & measurementsOPG, OPN, BMP-7, and fetuin-A were measured in blood samples from 602 incident dialysis patients recruited from United States dialysis centers between 1995 and 1998 as part of the Choices for Healthy Outcomes In Caring for ESRD Study. Their association with all-cause and cardiovascular mortality were assessed using Cox proportional hazards models adjusted for demographic characteristics, comorbidity, serum phosphate, and calcium. An interaction with diabetes was tested because of its known association with vascular calcification. Predictive accuracy of selected biomarkers was explored by C-statistics in nested models with training and validation subcohorts.ResultsHigher OPG and lower fetuin-A levels were associated with higher mortality over up to 13 years of follow-up (median, 3.4 years). The adjusted hazard ratios (HR) for highest versus lowest tertile were 1.49 (95% confidence interval [95% CI], 1.08 to 2.06) for OPG and 0.69 (95% CI, 0.52 to 0.92) for fetuin-A. In stratified models, the highest tertile of OPG was associated with higher mortality among patients without diabetes (HR, 2.42; 95% CI, 1.35 to 4.34), but not patients with diabetes (HR, 1.26; 95% CI, 0.82 to 1.93; P for interaction=0.001). In terms of cardiovascular mortality, higher fetuin-A was associated with lower risk (HR, 0.85 per 0.1 g/L: 95% CI, 0.75 to 0.96). In patients without diabetes, higher OPG was associated with greater risk (HR for highest versus lowest tertile, 2.91; 95% CI, 1.06 to 7.99), but not in patients with diabetes or overall. OPN and BMP-7 were not independently associated with outcomes overall. The addition of OPG and fetuin-A did not significantly improve predictive accuracy of mortality.ConclusionsOPG and fetuin-A may be risk factors for all-cause and cardiovascular mortality in patients undergoing dialysis, but do not improve risk prediction.