van Hateren Kornelis J J, Landman Gijs W D, Arnold Jarinke F H, Joosten Hanneke, Groenier Klaas H, Navis Gerjan J, Sparwasser Andrea, Bakker Stephan J L, Bilo Henk J G, Kleefstra Nanne
Diabetes Centre, Isala, Zwolle, the Netherlands.
Diabetes Centre, Isala, Zwolle, the Netherlands; Department of Internal Medicine, Gelre hospital, Apeldoorn, the Netherlands.
PLoS One. 2015 Jul 28;10(7):e0133065. doi: 10.1371/journal.pone.0133065. eCollection 2015.
Two previous studies concluded that proenkephalin A (PENK-A) had predictive capabilities for stroke severity, recurrent myocardial infarction, heart failure and mortality in patients with stroke and myocardial infarction.
This study aimed to investigate the value of PENK-A as a biomarker for predicting mortality in patients with type 2 diabetes mellitus.
Patients with type 2 diabetes mellitus were included from the prospective observational ZODIAC (Zwolle Outpatient Diabetes project Integrating Available Care) study. The present analysis incorporated two ZODIAC cohorts (1998 and 2001). Since blood was drawn for 1204 out of 1688 patients (71%), and information on relevant confounders was missing in 47 patients, the final sample comprised 1157 patients. Cox proportional hazard models were used for evaluating the relationship between PENK-A and (cardiovascular) mortality. Risk prediction capabilities were assessed with Harrell's C statistics and the integrated discrimination improvement (IDI).
After a follow-up period of 14 years, 525 (45%) out of 1157 patients had died, of which 224 (43%) were attributable to cardiovascular factors. Higher Log PENK-A levels were not independently associated with increased (cardiovascular) mortality. Patients with PENK-A values in the highest tertile had a 49% (95%CI 1%-121%) higher risk of cardiovascular mortality compared to patients in the reference category (lowest tertile). C-values were not different after removing PENK-A from the Cox models and there were no significant differences in IDI values.
The associations between PENK-A and mortality were strongly attenuated after accounting for all traditional risk factors. Furthermore, PENK-A did not seem to have additional value beyond conventional risk factors when predicting all-cause and cardiovascular mortality.
此前两项研究得出结论，前脑啡肽原A（PENK-A）对中风严重程度、复发性心肌梗死、心力衰竭以及中风和心肌梗死患者的死亡率具有预测能力。
本研究旨在探讨PENK-A作为预测2型糖尿病患者死亡率生物标志物的价值。
2型糖尿病患者来自前瞻性观察性ZODIAC（兹沃勒门诊糖尿病项目整合现有护理）研究。目前的分析纳入了两个ZODIAC队列（1998年和2001年）。由于1688名患者中有1204名（71%）抽取了血液，且47名患者缺少相关混杂因素的信息，最终样本包括1157名患者。采用Cox比例风险模型评估PENK-A与（心血管）死亡率之间的关系。用Harrell's C统计量和综合判别改善（IDI）评估风险预测能力。
经过14年的随访期，1157名患者中有525名（45%）死亡，其中224名（43%）归因于心血管因素。较高的Log PENK-A水平与（心血管）死亡率增加无独立相关性。与参考类别（最低三分位数）的患者相比，PENK-A值处于最高三分位数的患者心血管死亡风险高49%（95%CI 1%-121%）。从Cox模型中去除PENK-A后，C值无差异，IDI值也无显著差异。
在考虑所有传统风险因素后，PENK-A与死亡率之间的关联大幅减弱。此外，在预测全因死亡率和心血管死亡率时，PENK-A似乎没有超出传统风险因素的额外价值。
