Pregnancy-associated plasma protein-A (PAPP-A) and the proform of the eosinophil major basic protein (ProMBP) are associated with increased risk of death in heart failure patients
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Pregnancy-associated plasma protein-A (PAPP-A) and the proform of the eosinophil major basic protein (ProMBP) are associated with increased risk of death in heart failure patients. / Dembic, Maja; Hedley, Paula L; Torp-Pedersen, Christian; Køber, Lars; Christiansen, Michael.
In: Scandinavian Journal of Clinical & Laboratory Investigation, Vol. 77, No. 5, 2017, p. 352-357.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Pregnancy-associated plasma protein-A (PAPP-A) and the proform of the eosinophil major basic protein (ProMBP) are associated with increased risk of death in heart failure patients
AU - Dembic, Maja
AU - Hedley, Paula L
AU - Torp-Pedersen, Christian
AU - Køber, Lars
AU - Christiansen, Michael
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - Aged
KW - Aged, 80 and over
KW - Analysis of Variance
KW - Biomarkers/blood
KW - Diabetes Mellitus/physiopathology
KW - Echocardiography
KW - Eosinophil Major Basic Protein/blood
KW - Female
KW - Follow-Up Studies
KW - Heart Failure/blood
KW - Humans
KW - Insulin-Like Growth Factor I/metabolism
KW - Male
KW - Middle Aged
KW - Myocardial Ischemia/physiopathology
KW - Natriuretic Peptide, Brain/blood
KW - Pregnancy
KW - Pregnancy-Associated Plasma Protein-A/metabolism
KW - Prognosis
KW - Proportional Hazards Models
KW - Protein Precursors/blood
KW - Pulmonary Disease, Chronic Obstructive/physiopathology
KW - Risk Factors
U2 - 10.1080/00365513.2017.1325926
DO - 10.1080/00365513.2017.1325926
M3 - Journal article
C2 - 28537443
VL - 77
SP - 352
EP - 357
JO - Scandinavian Journal of Clinical & Laboratory Investigation
JF - Scandinavian Journal of Clinical & Laboratory Investigation
SN - 0036-5513
IS - 5
ER -
ID: 197003068