Department of Cardiovascular Medicine, Istituto Di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156, Milan, Italy.
Roche Diagnostics GmbH, Penzberg, Germany.
BMC Cardiovasc Disord. 2021 Nov 19;21(1):553. doi: 10.1186/s12872-021-02358-y.
Novel circulating biomarkers may help in understanding the underlying mechanisms of atrial fibrillation (AF), a challenge for AF management and prevention of cardiovascular (CV) events. Whether glycosylation affects the prognostic value of N-terminal pro-B type natriuretic peptide (NT-proBNP) in AF is still unknown.
To test how deglycosylated total NT-proBNP, NT-proBNP and a panel of biomarkers are associated with: (1) recurrent AF, (2) first hospitalization for CV reasons.
A total of 382 patients of the GISSI-AF trial in sinus rhythm with a history of AF, echocardiographic variables, total NT-proBNP, NT-proBNP and nine additional biomarkers [Total N-terminal pro-B type natriuretic peptide (Total NT proBNP), N-terminal pro-B type natriuretic peptide (NTproBNP), Angiopoietin 2 (Ang2), Bone morphogenic protein-10 (BMP10), Dickkopf-related protein-3 (DKK3), Endothelial cell specific molecule-1 (ESM1), Fatty acid-binding protein 3 (FABP3), Fibroblast growth factor 23 (FGF23), Growth differentiation factor-15 (GDF15), Insulin-like growth factor-binding protein-7 (IGFBP7) and Myosin binding protein C3 (MYPBC3)]. were assayed at baseline, 6 and 12 months under blind conditions in a laboratory at Roche Diagnostics, Penzberg, Germany. The associations between circulating biomarkers and AF at the 6- and 12-month visits, and their predictive value, were assessed in multivariable models with logistic regression analysis and Cox proportional hazards regression analysis. Biomarkers associations were modelled for 1SD increase in their level.
Over a median follow-up of 365 days, 203/382 patients (53.1%) had at least one recurrence of AF and 16.3% were hospitalized for CV reasons. Total NT-proBNP, NT-proBNP, Ang2 and BMP10 showed the strongest associations with ongoing AF. Natriuretic peptides also predicted recurrent AF (total NT-proBNP: HR:1.19[1.04-1.36], p = 0.026; NT-proBNP: HR:1.19[1.06-1.35], p = 0.016; Ang2: HR:1.07[0.95-1.20], p = 0.283; BMP10: HR:1.09[0.96-1.25], p = 0.249) and CV hospitalization (total NT-proBNP: HR:1.57[1.29-1.90], p < 0.001 1.63], p = 0.097).
The association of total NT-proBNP with the risk of AF first recurrence was similar to that of NT-proBNP, suggesting no influence of glycosylation. Analogous results were obtained for the risk of first hospitalization for CV reasons. Natriuretic peptides, Ang2 and BMP10 were associated with ongoing AF. Findings from the last two biomarkers point to a pathogenic role of cardiac extracellular matrix and cardiomyocyte growth in the myocardium of the right atrium and ventricle.
新型循环生物标志物可能有助于了解心房颤动（AF）的潜在机制，这是 AF 管理和预防心血管（CV）事件的一个挑战。糖基化是否影响 N 端脑利钠肽前体（NT-proBNP）在 AF 中的预后价值尚不清楚。
检测去糖基化总 NT-proBNP、NT-proBNP 和一组生物标志物与以下情况的相关性：（1）复发性 AF，（2）首次因 CV 原因住院。
GISSI-AF 试验中的 382 名窦性心律伴 AF 病史的患者，进行了超声心动图变量、总 NT-proBNP、NT-proBNP 和另外 9 种生物标志物[总 N 端脑利钠肽前体（总 NT proBNP）、脑利钠肽前体（NTproBNP）、血管生成素 2（Ang2）、骨形态发生蛋白 10（BMP10）、Dickkopf 相关蛋白 3（DKK3）、内皮细胞特异性分子 1（ESM1）、脂肪酸结合蛋白 3（FABP3）、成纤维细胞生长因子 23（FGF23）、生长分化因子 15（GDF15）、胰岛素样生长因子结合蛋白 7（IGFBP7）和肌球蛋白结合蛋白 C3（MYPBC3）]的检测，在罗氏诊断公司（德国彭茨贝格）的实验室中以盲法进行，基线、6 个月和 12 个月。采用多变量逻辑回归分析和 Cox 比例风险回归分析，评估生物标志物与 6 个月和 12 个月访视时 AF 的相关性及其预测价值。将生物标志物的相关性建模为其水平增加 1SD。
中位随访 365 天期间，382 例患者中有 203 例（53.1%）至少发生一次 AF 复发，16.3%因 CV 原因住院。总 NT-proBNP、NT-proBNP、Ang2 和 BMP10 与持续性 AF 相关性最强。利钠肽也预测了复发性 AF（总 NT-proBNP：HR：1.19[1.04-1.36]，p=0.026；NT-proBNP：HR：1.19[1.06-1.35]，p=0.016；Ang2：HR：1.07[0.95-1.20]，p=0.283；BMP10：HR：1.09[0.96-1.25]，p=0.249）和 CV 住院（总 NT-proBNP：HR：1.57[1.29-1.90]，p<0.001，1.63，p=0.097）。
总 NT-proBNP 与 AF 首次复发风险的相关性与 NT-proBNP 相似，提示糖基化无影响。对于首次因 CV 原因住院的风险，也得到了类似的结果。利钠肽、Ang2 和 BMP10 与持续性 AF 相关。后两种生物标志物的结果表明，心脏细胞外基质和心肌细胞生长在右心房和心室心肌中具有致病作用。
