Serum tenascin-C is independently associated with increased major adverse cardiovascular events and death in individuals with type 2 diabetes: a French prospective cohort
Serum tenascin-C is independently associated with increased major adverse cardiovascular events and death in individuals with type 2 diabetes: a French prospective cohort
复制标题
DOI：
10.1007/s00125-020-05108-5
复制
发表时间：
2020-02-10
期刊：
影响因子：
8.2
通讯作者：
Saulnier, Pierre-Jean
中科院分区：
文献类型：
--
作者：
Gellen, Barnabas;Thorin-Trescases, Nathalie;Saulnier, Pierre-Jean
Tenascin-C（TN-C）是一种细胞外基质糖蛋白，在炎症和心血管疾病中高度表达。血清TN-C尚未在2型糖尿病患者中进行专门研究，2型糖尿病是一种与慢性低度炎症和CV疾病风险增加相关的疾病。在这项研究中，我们假设2型糖尿病患者入组时血清TN-C升高与随访期间死亡和主要不良心血管事件（MACE）风险增加相关。方法我们使用了一个前瞻性、单中心队列，连续的2型糖尿病参与者（SURIGAENE [SUivi Renal，DIAbete de type 2 et GENEtique]队列），全因死亡作为主要终点，MACE（CV死亡、非致死性心肌梗死或卒中）作为次要终点。我们使用比例风险模型调整后的传统危险因素和相对综合辨别力改善（rIDI），以评估这些危险因素的TN-C的增量预测价值。结果：我们监测了1321名个体（58%为男性，平均年龄64 +/- 11岁），中位数为89个月。在随访期间，442人死亡，497人发生MACE。多变量考克斯分析显示，血清TN-C浓度与死亡风险增加（HR/1 SD：1.27 [95% CI 1.17，1.38]; p < 0.0001）和MACE风险增加（HR/1 SD：1.23 [95% CI 1.13，1.34]; p < 0.0001）相关。在传统风险因素之上使用TN-C浓度，全因死亡（rIDI：8.2%; p = 0.0006）和MACE（rIDI：6.7%; p = 0.0014）风险的预测显著改善，但适度。结论/解释在2型糖尿病患者中，血清TN-C浓度升高与死亡和MACE独立相关。因此，将TN-C作为预后生物标志物可以改善这些个体的风险分层。
Aims/hypothesis Tenascin-C (TN-C) is an extracellular matrix glycoprotein highly expressed in inflammatory and cardiovascular (CV) diseases. Serum TN-C has not yet been specifically studied in individuals with type 2 diabetes, a condition associated with chronic low-grade inflammation and increased CV disease risk. In this study, we hypothesised that elevated serum TN-C at enrolment in participants with type 2 diabetes would be associated with increased risk of death and major adverse CV events (MACE) during follow-up. Methods We used a prospective, monocentric cohort of consecutive type 2 diabetes participants (the SURDIAGENE [SUivi Renal, DIAbete de type 2 et GENEtique] cohort) with all-cause death as a primary endpoint and MACE (CV death, non-fatal myocardial infarction or stroke) as a secondary endpoint. We used a proportional hazard model after adjustment for traditional risk factors and the relative integrated discrimination improvement (rIDI) to assess the incremental predictive value of TN-C for these risk factors. Results We monitored 1321 individuals (58% men, mean age 64 +/- 11 years) for a median of 89 months. During follow-up, 442 individuals died and 497 had MACE. Multivariate Cox analysis showed that serum TN-C concentrations were associated with an increased risk of death (HR per 1 SD: 1.27 [95% CI 1.17, 1.38]; p < 0.0001) and MACE (HR per 1 SD: 1.23 [95% CI 1.13, 1.34]; p < 0.0001). Using TN-C concentrations on top of traditional risk factors, prediction of the risk of all-cause death (rIDI: 8.2%; p = 0.0006) and MACE (rIDI: 6.7%; p = 0.0014) improved significantly, but modestly. Conclusions/interpretation In individuals with type 2 diabetes, increased serum TN-C concentrations were independently associated with death and MACE. Therefore, including TN-C as a prognostic biomarker could improve risk stratification in these individuals.