Urinary Proteomics Pilot Study for Biomarker Discovery and Diagnosis in Heart Failure with Reduced Ejection Fraction.
BACKGROUND
Biomarker discovery and new insights into the pathophysiology of heart failure with reduced ejection fraction (HFrEF) may emerge from recent advances in high-throughput urinary proteomics. This could lead to improved diagnosis, risk stratification and management of HFrEF.


RESULTS
Urine samples were analyzed by on-line capillary electrophoresis coupled to electrospray ionization micro time-of-flight mass spectrometry (CE-MS) to generate individual urinary proteome profiles. In an initial biomarker discovery cohort, analysis of urinary proteome profiles from 33 HFrEF patients and 29 age- and sex-matched individuals without HFrEF resulted in identification of 103 peptides that were significantly differentially excreted in HFrEF. These 103 peptides were used to establish the support vector machine-based HFrEF classifier HFrEF103. In a subsequent validation cohort, HFrEF103 very accurately (area under the curve, AUC = 0.972) discriminated between HFrEF patients (N = 94, sensitivity = 93.6%) and control individuals with and without impaired renal function and hypertension (N = 552, specificity = 92.9%). Interestingly, HFrEF103 showed low sensitivity (12.6%) in individuals with diastolic left ventricular dysfunction (N = 176). The HFrEF-related peptide biomarkers mainly included fragments of fibrillar type I and III collagen but also, e.g., of fibrinogen beta and alpha-1-antitrypsin.


CONCLUSIONS
CE-MS based urine proteome analysis served as a sensitive tool to determine a vast array of HFrEF-related urinary peptide biomarkers which might help improving our understanding and diagnosis of heart failure.
Department of Cardiology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark.
Kasper
K
Rossing
Department of Cardio-, Nephro-, and Endocrinology, North Zealand Hospital, University of Copenhagen, Copenhagen, Denmark.
Helle Skovmand
HS
Bosselmann
Department of Cardiology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark.
Finn
F
Gustafsson
Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
Zhen-Yu
ZY
Zhang
Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
Yu-Mei
YM
Gu
Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
Tatiana
T
Kuznetsova
Mosaiques Diagnostics and Therapeutics AG, Hanover, Germany.
Esther
E
Nkuipou-Kenfack
Mosaiques Diagnostics and Therapeutics AG, Hanover, Germany.|Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.
Harald
H
Mischak
Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
Jan A
JA
Staessen
Mosaiques Diagnostics and Therapeutics AG, Hanover, Germany.
Thomas
T
Koeck
Institute for Clinical Medicine, Herlev Hospital, Herlev, Denmark.
Morten
M
Schou
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000652:urine*; D005260:Female; D006333:Heart Failure / Q000235:genetics / Q000473:pathology / Q000652:urine*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000235:genetics / Q000652:urine*; D040901:Proteomics; D021241:Spectrometry, Mass, Electrospray Ionization; D013318:Stroke Volume; D060388:Support Vector Machine
D015415:Biomarkers; D010446:Peptide Fragments