N末端B型利钠肽原和高敏C反应蛋白在心脏移植术后排斥反应中的意义

目的 分析原位心脏移植术后心内膜心肌活检(EMB)结果 与血N末端B型利钠肽原(NT-proBNP)和高敏C反应蛋白(hs-CRP)水平的关系,评价NT-proBNP和hs-CBP在诊断心脏移植术后排斥反应中的作用.方法 回顾分析阜外心血管病医院自2004年6月至2007年1月61例原位心脏移植患者术后3周、3～4个月、5～6个月、12个月的EMB及每次EMB前的血NT-proBNP和hs-CRP检查结果 ,分析NT-proBNP和hs-CRP与排斥反应之间的相关性.结果 NT-proBNP浓度于术后随时间推移呈下降趋势(r=-0.520,P=0.000),术后半年内NT-proBNP水平明显高于半年以后(P=0.002).排斥反应阳性组(病理分级≥2级)的NT-proBNP浓度高于阴性组(P=0.073);在排除时间影响之后,两组NT-proBNP浓度差异有统计学意义(P=0.025).NT-proBNP测定值的受试者工作特征(ROC)曲线显示,曲线下面积(AUC)为0.566(P=0.344).界值(cutoff值)为6.00×10-16mol/L时,其敏感性、特异性分别为57.1%、44.8%;cutoff值为8.00×10-16mot/L时,其敏感性、特异性分别为38.1%、61.0%.术后半年内hs-CRP水平高于半年以后(P=0.069).排斥反应阳性组的hs-CRP浓度高于阴性组(P=0.138);在排除时间影响之后,两组hs-CRP浓度差异仍无统计学意义(P=0.073).分别以NT-proBNP 4.00×10-16mol/ L和hs-CRP 3 ms/ L为分界点,NT-proBNP和hs-CRP同时高于分界点的有20例次(病理分级≥2级有5例次),而NT-proBNP和hs-CRP同时低于分界点的有26例次(病理分级≥2级有3例次),两者差异无统计学意义(P=0.232).结论 NT-proBNP浓度于心脏移植术后呈下降趋势,术后NT-proBNP浓度升高与排斥反应有相关性,但其诊断排斥反应的价值较低.心脏移植术后hs-CRP浓度升高与排斥反应无明显相关性,其与NT-proBNP一起不能提高诊断排斥反应的准确性.

Association between serum NT-proBNP/hs-CRP and acute rejection after heart transplantation

Objective The aim of the present work was to investigate the potential relationship between acute rejection and serum concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP)/high sensitivity C reactive protein (hs-CRP) in post-transplant patients. Methods Sixty-one consecutive orthotopic heart transplantation recipients were prospectively recruited from the cardiac transplantation programme at Fuwai Hospital Endomyocardial biopsies (EMB) were performed routinely at 3 weeks, 3, 6 and 12 months after transplantation. EMB were also performed when patients had new symptoms of heart failure or at 2 weeks after steroid pulse therapy. Serum NT-proBNP and hs-CRP were simultaneously measured before EMB procedure. Results A total of 126 biopsy samples were obtained from the 61 patients.Serum NT-proBNP concentrations progressively decreased after transplantation (spearman correlation coefficient-0.520, P=0.000). NT-proBNP levels within 6 months after transplantation were significantly higher than those beyond 6 months post transplantation [(11.86±11.16 ) × 10-16 mol/L vs. (5.83 ± 6.58) × 10-16 mol/L,P=0.002]. NT-proBNP concentrations in patients with rejection tended to be higher than patients without rejection (13.68 × 10-16 mol/L vs. 9.26 × 10-16 mol/L, P=0.073 ). After time adjustment, the difference of NT-proBNP concentrations between patients with or without rejection becomes statistically significant (14. 45 x 10-16 mol/L vs. 9.1 x 10-16 mol/L, P=0.025 ). Receiver operating characteristics analysis for NT-proBNP versus rejection grade revealed an area under the curve of 0.566,indicating a low predictive value for NT-proBNP. A cutoff of 6.00 x 10-16 mol/L yielded poor specificity (44.8% ) and sensitivity (57.1% ), the sensitivity and specificity were 38.1% and 61.0%, respectively with a cutoff of 8.00 x 10-16 mol/L, hs-CRP levels within 6 months after transplantation tended to be higher than those beyond 6 months [(2.39 ± 3.90) mg/L vs. (1.34 ± 2.73) mg/L, P=0.069] . hs-CRP concentrations in patients with rejection were similar as patients without rejection (2.995 mg/L vs. 1.833 mg/L, P=0.138). The incidence of rejeetion was similar in patients with two higher biomarkers (5/20,25%) compared to patients with two low biomarkers (3/26, 11.5%, P=0.232). Conclusions NT-proBNP level decreased after transplantation. Although increased NT-proBNP coneentrations were related to rejection, the diagnostic capacity was low. Elevated hs-CRP concentrations were not related to rejection after heart transplantation.