Dembic Maja, Hedley Paula L, Torp-Pedersen Christian, Køber Lars, Christiansen Michael
a Department for Congenital Disorders , Statens Serum Institut , Copenhagen , Denmark.
b Department of Biomedical Sciences , University of Copenhagen , Copenhagen , Denmark.
Scand J Clin Lab Invest. 2017 Sep;77(5):352-357. doi: 10.1080/00365513.2017.1325926. Epub 2017 May 24.
Risk stratification and patient management in heart failure (HF) is difficult due to the unpredictable progression of the disease, necessitating the development of reliable diagnostic biomarkers to facilitate decision-making in clinical practice. Pregnancy-associated plasma protein-A (PAPP-A) is a marker of arteriosclerotic heart disease. PAPP-A is a serum protease, which is involved in the insulin-like growth factor 1 (IGF-1) axis where it is inhibited by the proform of the eosinophil major basic protein (proMBP). In this study, we evaluated serum PAPP-A and proMBP as long-term prognostic biomarkers of all-cause mortality in HF. Serum PAPP-A and proMBP concentrations were determined in 683 patients with NYHA III-IV HF recruited in the EchoCardiography and Heart Study (ECHOS) in Denmark. The mean age of the patients (73% male) was 70 at admission. During 7 years of follow-up, 516 patients died. In univariate analysis, both PAPP-A and proMBP, divided into quartiles, showed significant association with mortality. Using a Cox proportional hazard model, hazard ratios for continuous values of PAPP-A and proMBP were HR = 1.42 (CI = 1.23-1.64, p < 0.0001) and HR = 1.36 (CI = 1.22-1.51, p <0.0001), respectively. However, neither PAPP-A nor proMBP were significant independent predictors when the model included age, gender, brain-type natriuretic peptide, medical history of HF, ischemic heart disease, chronic obstructive pulmonary disease, and diabetes mellitus. In conclusion, high levels of PAPP-A and proMBP are associated with increased risk of death from all causes in HF and are potential prognostic markers of adverse outcomes in HF patients.
由于心力衰竭（HF）病情进展不可预测，其风险分层和患者管理颇具难度，因此需要开发可靠的诊断生物标志物，以促进临床实践中的决策制定。妊娠相关血浆蛋白A（PAPP-A）是动脉粥样硬化性心脏病的标志物。PAPP-A是一种血清蛋白酶，参与胰岛素样生长因子1（IGF-1）轴，在该轴中它受到嗜酸性粒细胞主要碱性蛋白前体（proMBP）的抑制。在本研究中，我们评估了血清PAPP-A和proMBP作为HF全因死亡率的长期预后生物标志物。在丹麦的超声心动图与心脏研究（ECHOS）中，对683例纽约心脏协会（NYHA）III-IV级HF患者测定了血清PAPP-A和proMBP浓度。患者的平均年龄为70岁（男性占73%），入院时进行了测定。在7年的随访期间，516例患者死亡。在单因素分析中，PAPP-A和proMBP按四分位数划分，均与死亡率显著相关。使用Cox比例风险模型，PAPP-A和proMBP连续值的风险比分别为HR = 1.42（CI = 1.23 - 1.64，p < 0.0001）和HR = 1.36（CI = 1.22 - 1.51，p < 0.0001）。然而，当模型纳入年龄、性别、脑钠肽、HF病史、缺血性心脏病、慢性阻塞性肺疾病和糖尿病时，PAPP-A和proMBP均不是显著的独立预测因子。总之，高水平的PAPP-A和proMBP与HF患者全因死亡风险增加相关，是HF患者不良结局的潜在预后标志物。
