Kristen Arnt V, Rosenberg Mark, Lindenmaier David, Merkle Corina, Steen Henning, Andre Florian, Schönland Stefan O, Schnabel Philipp A, Schuster Tibor, Röcken Christoph, Giannitsis Evangelos, Katus Hugo A, Frey Norbert
Department of Cardiology, Angiology, and Respiratory Medicine, Heidelberg University , Heidelberg , Germany .
Amyloid. 2014 Sep;21(3):202-10. doi: 10.3109/13506129.2014.940457. Epub 2014 Jul 9.
Troponin-T (cTnT) and NT-proBNP provide prognostic information in light-chain amyloidosis (AL). Thus, these biomarkers are widely used in clinical routine for risk stratification. Recently, plasma level of osteopontin (OPN), a secreted phosphoglycoprotein expressed by a variety of cell types, has been reported as a risk predictor in various cardiovascular diseases.
OPN was determined retrospectively in 150 consecutive patients newly diagnosed with AL amyloidosis. All patients were evaluated according to a routine protocol including electrocardiography, echocardiography and laboratory testing.
Mean OPN was 591 ± 37 ng/mL. Cardiac involvement was established in 83 (55.3%). Median OPN plasma level were associated with number of organs involved, renal function, eligibility for high-dose melphalan chemotherapy and autologous stem cell transplantation, and severity of cardiac amyloidosis. Median follow-up was 19.2 months. 1-year all-cause-survival was 83.4%. The cut-offs discriminating 1-year all-cause-mortality for NT-proBNP, troponin T, and OPN were 2544 ng/L, 0.035 µg/L, and 426.8 ng/mL, respectively. Outcome was worse in patients with biomarkers above the individual ROC derived cut-off. A significant improvement of survival was observed in patients with cTNT >0.035 µg/L or NT-proBNP >2544 ng/L and OPN below ROC-derived cut-off of 426.8 ng/mL as compared to patients with OPN above 426.8 ng/L. No further discrimination was achieved by OPN in the cohorts of low troponin T or low NT-proBNP, respectively. Separate multivariate models identified OPN (cut-off 426.8 ng/mL) and troponin T (cut-off 0.035 µg/L) as independent predictors of all-cause-mortality.
These data demonstrated that OPN appears to be a valuable marker in the clinical routine for evaluation of patients with AL amyloidosis, especially if it is used in combination with cTNT and/or NT-proBNP.
肌钙蛋白T(cTnT)和N末端脑钠肽前体(NT-proBNP)可提供轻链淀粉样变性(AL)的预后信息。因此,这些生物标志物在临床常规中被广泛用于风险分层。最近,骨桥蛋白(OPN)的血浆水平,一种由多种细胞类型表达的分泌型磷酸糖蛋白,已被报道为各种心血管疾病的风险预测指标。
对150例新诊断为AL淀粉样变性的连续患者进行回顾性测定OPN。所有患者均按照包括心电图、超声心动图和实验室检查在内的常规方案进行评估。
OPN平均水平为591±37 ng/mL。83例(55.3%)存在心脏受累。OPN血浆中位数水平与受累器官数量、肾功能是否适合高剂量美法仑化疗及自体干细胞移植以及心脏淀粉样变性的严重程度相关。中位随访时间为19.2个月。1年全因生存率为83.4%。NT-proBNP、肌钙蛋白T和OPN区分1年全因死亡率的临界值分别为2544 ng/L、0.035 μg/L和426.8 ng/mL。生物标志物高于个体ROC得出的临界值的患者预后较差。与OPN高于426.8 ng/L的患者相比,cTNT>0.035 μg/L或NT-proBNP>2544 ng/L且OPN低于ROC得出的426.8 ng/mL临界值的患者生存率有显著提高。在低肌钙蛋白T或低NT-proBNP队列中,OPN未进一步显示出区分能力。单独多变量模型确定OPN(临界值426.8 ng/mL)和肌钙蛋白T(临界值0.035 μg/L)为全因死亡率的独立预测指标。
这些数据表明,OPN似乎是临床常规中评估AL淀粉样变性患者的一个有价值的标志物,特别是当它与cTNT和/或NT-proBNP联合使用时。