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Serum tenascin-C is independently associated with increased major adverse cardiovascular events and death in individuals with type 2 diabetes: a French prospective cohort.
Diabetologia ( IF 8.2 ) Pub Date : 2020-02-10 , DOI: 10.1007/s00125-020-05108-5
Barnabas Gellen 1 , Nathalie Thorin-Trescases 2 , Eric Thorin 2, 3 , Elise Gand 4 , Philippe Sosner 4, 5, 6 , Sonia Brishoual 4 , Vincent Rigalleau 7 , David Montaigne 8, 9 , Vincent Javaugue 4, 10 , Yann Pucheu 11 , Philippe Gatault 12 , Xavier Piguel 13 , Samy Hadjadj 12, 14 , Pierre-Jean Saulnier 4 ,
Affiliation  

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 Rénal, DIAbète 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.

中文翻译:

血清肌腱蛋白-C与2型糖尿病患者的主要不良心血管事件增加和死亡独立相关:法国前瞻性队列研究。

目的/假设腱糖蛋白C(TN-C)是一种细胞外基质糖蛋白,在炎症和心血管(CV)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,该疾病与慢性低度炎症和CV疾病风险增加有关。在这项研究中,我们假设2型糖尿病参与者入组时血清TN-C升高与随访期间死亡风险和重大不良CV事件(MACE)的发生有关。方法我们采用连续性2型糖尿病参与者(SURDIAGENE [SUiviRénal,DIAbètede type 2 et GENEtique]队列)的前瞻性,单中心队列,以全因死亡为主要终点,并采用MACE(CV死亡,非致命性心肌梗塞)或中风)作为次要终点。在对传统风险因素进行调整后,我们使用了比例风险模型,并使用了相对综合歧视改善(rIDI)来评估TN-C对这些风险因素的递增预测价值。结果我们监测了1321名个体(58%的男性,平均年龄64±11岁),中位数为89个月。在随访期间,有442人死亡,有497人患有MACE。多变量Cox分析显示,血清TN-C浓度与死亡风险增加(每1 SD HR:1.27 [95%CI 1.17,1.38]; p <0.0001)和MACE(每1 SD HR:1.23 [95%])相关。 CI 1.13,1.34]; p <0.0001)。使用除传统风险因素之外的TN-C浓度,对全因死亡风险(rIDI:8.2%; p = 0.0006)和MACE(rIDI:6.7%; p = 0.0014)的预测显着提高,但幅度不大。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,包括TN-C作为预后生物标志物可以改善这些个体的危险分层。
更新日期:2020-04-22
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