PMID- 28100627
OWN - NLM
STAT- MEDLINE
DCOM- 20171030
LR  - 20171030
IS  - 1942-3268 (Electronic)
IS  - 1942-3268 (Linking)
VI  - 10
IP  - 1
DP  - 2017 Feb
TI  - Inflammatory Biomarkers Predict Heart Failure Severity and Prognosis in Patients 
      With Heart Failure With Preserved Ejection Fraction: A Holistic Proteomic 
      Approach.
LID - e001633 [pii]
LID - 10.1161/CIRCGENETICS.116.001633 [doi]
AB  - BACKGROUND: Underlying mechanisms in heart failure (HF) with preserved ejection 
      fraction remain unknown. We investigated cardiovascular plasma biomarkers in HF 
      with preserved ejection fraction and their correlation to diastolic dysfunction, 
      functional class, pathophysiological processes, and prognosis. METHODS AND 
      RESULTS: In 86 stable patients with HF and EF >/=45% in the Karolinska Rennes 
      (KaRen) biomarker substudy, biomarkers were quantified by a multiplex 
      immunoassay. Orthogonal projection to latent structures by partial least square 
      analysis was performed on 87 biomarkers and 240 clinical variables, ranking 
      biomarkers associated with New York Heart Association (NYHA) Functional class and 
      the composite outcome (all-cause mortality and HF hospitalization). Biomarkers 
      significantly correlated with outcome were analyzed by multivariable Cox 
      regression and correlations with echocardiographic measurements performed. The 
      orthogonal partial least square outcome-predicting biomarker pattern was run 
      against the Ingenuity Pathway Analysis (IPA) database, containing annotated data 
      from the public domain. The orthogonal partial least square analyses identified 
      32 biomarkers correlated with NYHA class and 28 predicting outcomes. Among 
      outcome-predicting biomarkers, growth/differentiation factor-15 was the strongest 
      and an additional 7 were also significant in Cox regression analyses when 
      adjusted for age, sex, and N-terminal probrain natriuretic peptide: 
      adrenomedullin (hazard ratio per log increase 2.53), agouti-related protein; 
      (1.48), chitinase-3-like protein 1 (1.35), C-C motif chemokine 20 (1.35), fatty 
      acid-binding protein (1.33), tumor necrosis factor receptor 1 (2.29), and 
      TNF-related apoptosis-inducing ligand (0.34). Twenty-three of them correlated 
      with diastolic dysfunction (E/e') and 5 with left atrial volume index. The IPA 
      suggested that increased inflammation, immune activation with decreased necrosis 
      and apoptosis preceded poor outcome. CONCLUSIONS: In HF with preserved ejection 
      fraction, novel biomarkers of inflammation predict HF severity and prognosis that 
      may complement or even outperform traditional markers, such as N-terminal 
      probrain natriuretic peptide. These findings lend support to a hypothesis 
      implicating global systemic inflammation in HF with preserved ejection fraction. 
      CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov; Unique 
      identifier: NCT00774709.
CI  - (c) 2017 American Heart Association, Inc.
FAU - Hage, Camilla
AU  - Hage C
AD  - From the Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden 
      (C.H., C.L., L.H.L.); Department of Cardiology, Karolinska University Hospital, 
      Stockholm, Sweden (C.H., C.L., L.H.L.); Cardiovascular and Metabolic Diseases, 
      Innovative Medicines and Early Development Biotech Unit, AstraZeneca R&D, 
      Molndal, Sweden (E.M., L.-M.G.); Departement de Cardiologie and CIC-IT U 804, 
      Centre Hospitalier Universitaire de Rennes, France (E.D., J.-C.D.); and 
      Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska 
      Academy at the University of Gothenburg, Sweden (L.-M.G.). 
      camilla.hage@karolinska.se.
FAU - Michaelsson, Erik
AU  - Michaelsson E
AD  - From the Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden 
      (C.H., C.L., L.H.L.); Department of Cardiology, Karolinska University Hospital, 
      Stockholm, Sweden (C.H., C.L., L.H.L.); Cardiovascular and Metabolic Diseases, 
      Innovative Medicines and Early Development Biotech Unit, AstraZeneca R&D, 
      Molndal, Sweden (E.M., L.-M.G.); Departement de Cardiologie and CIC-IT U 804, 
      Centre Hospitalier Universitaire de Rennes, France (E.D., J.-C.D.); and 
      Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska 
      Academy at the University of Gothenburg, Sweden (L.-M.G.).
FAU - Linde, Cecilia
AU  - Linde C
AD  - From the Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden 
      (C.H., C.L., L.H.L.); Department of Cardiology, Karolinska University Hospital, 
      Stockholm, Sweden (C.H., C.L., L.H.L.); Cardiovascular and Metabolic Diseases, 
      Innovative Medicines and Early Development Biotech Unit, AstraZeneca R&D, 
      Molndal, Sweden (E.M., L.-M.G.); Departement de Cardiologie and CIC-IT U 804, 
      Centre Hospitalier Universitaire de Rennes, France (E.D., J.-C.D.); and 
      Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska 
      Academy at the University of Gothenburg, Sweden (L.-M.G.).
FAU - Donal, Erwan
AU  - Donal E
AD  - From the Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden 
      (C.H., C.L., L.H.L.); Department of Cardiology, Karolinska University Hospital, 
      Stockholm, Sweden (C.H., C.L., L.H.L.); Cardiovascular and Metabolic Diseases, 
      Innovative Medicines and Early Development Biotech Unit, AstraZeneca R&D, 
      Molndal, Sweden (E.M., L.-M.G.); Departement de Cardiologie and CIC-IT U 804, 
      Centre Hospitalier Universitaire de Rennes, France (E.D., J.-C.D.); and 
      Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska 
      Academy at the University of Gothenburg, Sweden (L.-M.G.).
FAU - Daubert, Jean-Claude
AU  - Daubert JC
AD  - From the Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden 
      (C.H., C.L., L.H.L.); Department of Cardiology, Karolinska University Hospital, 
      Stockholm, Sweden (C.H., C.L., L.H.L.); Cardiovascular and Metabolic Diseases, 
      Innovative Medicines and Early Development Biotech Unit, AstraZeneca R&D, 
      Molndal, Sweden (E.M., L.-M.G.); Departement de Cardiologie and CIC-IT U 804, 
      Centre Hospitalier Universitaire de Rennes, France (E.D., J.-C.D.); and 
      Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska 
      Academy at the University of Gothenburg, Sweden (L.-M.G.).
FAU - Gan, Li-Ming
AU  - Gan LM
AD  - From the Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden 
      (C.H., C.L., L.H.L.); Department of Cardiology, Karolinska University Hospital, 
      Stockholm, Sweden (C.H., C.L., L.H.L.); Cardiovascular and Metabolic Diseases, 
      Innovative Medicines and Early Development Biotech Unit, AstraZeneca R&D, 
      Molndal, Sweden (E.M., L.-M.G.); Departement de Cardiologie and CIC-IT U 804, 
      Centre Hospitalier Universitaire de Rennes, France (E.D., J.-C.D.); and 
      Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska 
      Academy at the University of Gothenburg, Sweden (L.-M.G.).
FAU - Lund, Lars H
AU  - Lund LH
AD  - From the Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden 
      (C.H., C.L., L.H.L.); Department of Cardiology, Karolinska University Hospital, 
      Stockholm, Sweden (C.H., C.L., L.H.L.); Cardiovascular and Metabolic Diseases, 
      Innovative Medicines and Early Development Biotech Unit, AstraZeneca R&D, 
      Molndal, Sweden (E.M., L.-M.G.); Departement de Cardiologie and CIC-IT U 804, 
      Centre Hospitalier Universitaire de Rennes, France (E.D., J.-C.D.); and 
      Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska 
      Academy at the University of Gothenburg, Sweden (L.-M.G.).
LA  - eng
SI  - ClinicalTrials.gov/NCT00774709
PT  - Journal Article
PT  - Multicenter Study
PT  - Observational Study
PL  - United States
TA  - Circ Cardiovasc Genet
JT  - Circulation. Cardiovascular genetics
JID - 101489144
RN  - 0 (Biomarkers)
RN  - 0 (Inflammation Mediators)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers/blood
MH  - Databases, Protein
MH  - Echocardiography
MH  - Female
MH  - France
MH  - Heart Failure/blood/*diagnosis/mortality/physiopathology
MH  - Humans
MH  - Inflammation Mediators/*blood
MH  - Least-Squares Analysis
MH  - Male
MH  - Multivariate Analysis
MH  - Predictive Value of Tests
MH  - Prognosis
MH  - Proportional Hazards Models
MH  - Prospective Studies
MH  - Proteomics/*methods
MH  - Risk Factors
MH  - Severity of Illness Index
MH  - *Stroke Volume
MH  - Sweden
MH  - *Ventricular Function, Left
OTO - NOTNLM
OT  - apoptosis
OT  - biomarkers
OT  - inflammation
OT  - prognosis
OT  - proteomics
EDAT- 2017/01/20 06:00
MHDA- 2017/10/31 06:00
CRDT- 2017/01/20 06:00
PHST- 2016/04/29 00:00 [received]
PHST- 2016/11/29 00:00 [accepted]
PHST- 2017/01/20 06:00 [entrez]
PHST- 2017/01/20 06:00 [pubmed]
PHST- 2017/10/31 06:00 [medline]
AID - CIRCGENETICS.116.001633 [pii]
AID - 10.1161/CIRCGENETICS.116.001633 [doi]
PST - ppublish
SO  - Circ Cardiovasc Genet. 2017 Feb;10(1):e001633. doi: 
      10.1161/CIRCGENETICS.116.001633.