Martos Ramón, Baugh John, Ledwidge Mark, O'Loughlin Christina, Murphy Niamh F, Conlon Carmel, Patle Anil, Donnelly Seamas C, McDonald Kenneth
Heart Failure Unit, School of Medicine and Medical Science, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland.
Eur J Heart Fail. 2009 Feb;11(2):191-7. doi: 10.1093/eurjhf/hfn036.
Heart failure with preserved ejection fraction (HF-PEF) can be difficult to diagnose in clinical practice. Myocardial fibrosis is a major determinant of diastolic dysfunction (DD), potentially contributing to the progression of HF-PEF. The aim of this study was to analyse whether serological markers of collagen turnover may predict HF-PEF and DD.
We included 85 Caucasian treated hypertensive patients (DD n=65; both DD and HF-PEF n=32). Serum carboxy (PICP), amino (PINP), and carboxytelo (CITP) peptides of procollagen type I, amino (PIIINP) peptide of procollagen type III, matrix metalloproteinases (MMP-1, MMP-2, and MMP-9), and tissue inhibitor of MMP levels were assayed. Using receiver operating characteristic curve analysis, MMP-2 (AUC=0.91; 95% CI: 0.84, 0.98), CITP (0.83; 0.72, 0.92), PICP (0.82; 0.72, 0.92), B-type natriuretic peptide (BNP) (0.82; 0.73, 0.91), MMP-9 (0.79; 0.68, 0.89), and PIIINP (0.78; 0.66, 0.89) levels were significant predictors of HF-PEF (P<0.01 for all). Carboxytelo peptides of procollagen type I (AUC=0.74; 95% CI: 0.62, 0.86), MMP-2 (0.73; 0.62, 0.84), PIIINP (0.73; 0.60, 0.85), BNP (0.69; 0.55, 0.83) and PICP (0.66; 0.54, 0.78) levels were significant predictors of DD (P<0.05 for all). A cutoff of 1585 ng/mL for MMP-2 provided 91% sensitivity and 76% specificity for predicting HF-PEF and combinations of biomarkers could be used to adjust either sensitivity or specificity.
Markers of collagen turnover identify patients with HF-PEF and DD. Matrix metalloproteinase 2 may be more useful than BNP in the identification of HF-PEF. This suggests that these new biochemical tools may assist in identifying patients with these diagnostically challenging conditions.
射血分数保留的心力衰竭(HF-PEF)在临床实践中可能难以诊断。心肌纤维化是舒张功能障碍(DD)的主要决定因素,可能促使HF-PEF进展。本研究的目的是分析胶原蛋白周转的血清学标志物是否可预测HF-PEF和DD。
我们纳入了85例接受治疗的白种人高血压患者(DD患者65例;DD和HF-PEF患者32例)。检测了血清I型前胶原羧基(PICP)、氨基(PINP)和羧基末端(CITP)肽、III型前胶原氨基(PIIINP)肽、基质金属蛋白酶(MMP-1、MMP-2和MMP-9)以及MMP组织抑制剂水平。使用受试者工作特征曲线分析,MMP-2(曲线下面积[AUC]=0.91;95%置信区间[CI]:0.84,0.98)、CITP(0.83;0.72,0.92)、PICP(0.82;0.72,0.92)、B型利钠肽(BNP)(0.82;0.73,0.91)、MMP-9(0.79;0.68,0.89)和PIIINP(0.78;0.66,0.89)水平是HF-PEF的显著预测指标(所有P<0.01)。I型前胶原羧基末端肽(AUC=0.74;95%CI:0.62,0.86)、MMP-2(0.73;0.62,0.84)、PIIINP(0.73;0.60,0.85)、BNP(0.69;0.55,0.83)和PICP(0.66;0.54,0.78)水平是DD的显著预测指标(所有P<0.05)。MMP-2的截断值为1585 ng/mL时,预测HF-PEF的灵敏度为91%,特异度为76%,生物标志物组合可用于调整灵敏度或特异度。
胶原蛋白周转标志物可识别HF-PEF和DD患者。基质金属蛋白酶2在识别HF-PEF方面可能比BNP更有用。这表明这些新的生化工具可能有助于识别患有这些诊断具有挑战性疾病的患者。