PMID- 29138270
OWN - NLM
STAT- MEDLINE
DCOM- 20190812
LR  - 20190812
IS  - 1530-8561 (Electronic)
IS  - 0009-9147 (Linking)
VI  - 64
IP  - 3
DP  - 2018 Mar
TI  - Low- and High-renin Heart Failure Phenotypes with Clinical Implications.
PG  - 597-608
LID - 10.1373/clinchem.2017.278705 [doi]
AB  - BACKGROUND: Blockade of the renin-angiotensin system (RAS) represents a main 
      strategy in the therapy of heart failure with reduced ejection fraction (HFrEF), 
      but the role of active renin concentration (ARC) for guiding therapy in the 
      presence of an RAS blockade remains to be established. This study assessed 
      angiotensin profiles of HFrEF patients with distinct RAS activations as reflected 
      by ARC. METHODS: Two cohorts of stable chronic HFrEF patients on optimal medical 
      treatment (OMT) were enrolled. We assessed ARC and all known circulating 
      angiotensin metabolites, including AngI and AngII, by mass spectrometry to 
      investigate the effect of different therapy modalities. Low- and high-renin HFrEF 
      patients were identified by ARC screening and subsequently characterized by their 
      angiotensin profiles. RESULTS: Although different modes of RAS blockade resulted 
      in typical AngII/AngI ratios, concentrations of (AngI+AngII) strongly correlated 
      with ARC [r = 0.95, P < 0.001] independent of therapy mode. Despite RAS blocker 
      treatment with angiotensin-converting enzyme inhibitors (ACE-I) or angiotensin II 
      type 1 receptor blockers (ARB), which anticipated ARC upregulation, about 30% of 
      patients showed lower/normal range ARC values. ARC did not correlate with 
      N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations and New York 
      Heart Association (NYHA) stages. Angiotensin concentrations were profoundly 
      diminished for the low-ARC group compared with the high-ARC group: AngI [6.4 ng/L 
      (IQR: 2.1-12.5) vs 537.9 ng/L (IQR: 423.1-728.4), P < 0.001 for ACE-I; and 4.5 
      ng/L (IQR: 1.4-11.2) vs 203.0 ng/L (IQR: 130.2-247.9), P = 0.003 for ARB] and 
      AngII [<1.4 ng/L (IQR: <1.4-1.5) vs 6.1 ng/L (IQR: 2.0-11.1), P = 0.002 for ACE-I 
      and 4.7 ng/L (IQR: <1.4-12.3) vs 206.4 ng/L (IQR: 142.2-234.4), P < 0.001 for 
      ARB]. CONCLUSIONS: In addition to NT-proBNP and NYHA stages, ARC enables 
      classification of HFrEF patients receiving OMT into more distinguished 
      neurohumoral HFrEF phenotypes, offering a rationale for adaptive therapeutic 
      interventions.
CI  - (c) 2017 American Association for Clinical Chemistry.
FAU - Pavo, Noemi
AU  - Pavo N
AD  - Department of Internal Medicine II, Clinical Division of Cardiology, Medical 
      University of Vienna, Vienna, Austria.
FAU - Goliasch, Georg
AU  - Goliasch G
AD  - Department of Internal Medicine II, Clinical Division of Cardiology, Medical 
      University of Vienna, Vienna, Austria.
FAU - Wurm, Raphael
AU  - Wurm R
AD  - Department of Internal Medicine II, Clinical Division of Cardiology, Medical 
      University of Vienna, Vienna, Austria.
FAU - Novak, Johannes
AU  - Novak J
AD  - Department of Internal Medicine II, Clinical Division of Cardiology, Medical 
      University of Vienna, Vienna, Austria.
FAU - Strunk, Guido
AU  - Strunk G
AD  - Complexity Research, Vienna, Austria; FH Campus Vienna, Vienna, Austria, and 
      Technical University Dortmund, Dortmund, Germany.
FAU - Gyongyosi, Mariann
AU  - Gyongyosi M
AD  - Department of Internal Medicine II, Clinical Division of Cardiology, Medical 
      University of Vienna, Vienna, Austria.
FAU - Poglitsch, Marko
AU  - Poglitsch M
AD  - Attoquant Diagnostics, Vienna, Austria.
FAU - Saemann, Marcus D
AU  - Saemann MD
AD  - Department of Internal Medicine III, Clinical Division of Nephrology, Medical 
      University of Vienna, Vienna, Austria.
FAU - Hulsmann, Martin
AU  - Hulsmann M
AD  - Department of Internal Medicine II, Clinical Division of Cardiology, Medical 
      University of Vienna, Vienna, Austria; martin.huelsmann@meduniwien.ac.at.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171114
PL  - England
TA  - Clin Chem
JT  - Clinical chemistry
JID - 9421549
RN  - 0 (Angiotensin-Converting Enzyme Inhibitors)
RN  - 0 (Peptide Fragments)
RN  - 0 (pro-brain natriuretic peptide (1-76))
RN  - 11128-99-7 (Angiotensin II)
RN  - 114471-18-0 (Natriuretic Peptide, Brain)
RN  - 9041-90-1 (Angiotensin I)
RN  - EC 3.4.23.15 (Renin)
MH  - Aged
MH  - Angiotensin I/blood
MH  - Angiotensin II/blood
MH  - Angiotensin-Converting Enzyme Inhibitors/therapeutic use
MH  - Female
MH  - Heart Failure/blood/*drug therapy
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Natriuretic Peptide, Brain/blood
MH  - Peptide Fragments/blood
MH  - Phenotype
MH  - Renin/*blood
MH  - Renin-Angiotensin System/drug effects
EDAT- 2017/11/16 06:00
MHDA- 2019/08/14 06:00
CRDT- 2017/11/16 06:00
PHST- 2017/07/16 00:00 [received]
PHST- 2017/10/23 00:00 [accepted]
PHST- 2017/11/16 06:00 [pubmed]
PHST- 2019/08/14 06:00 [medline]
PHST- 2017/11/16 06:00 [entrez]
AID - clinchem.2017.278705 [pii]
AID - 10.1373/clinchem.2017.278705 [doi]
PST - ppublish
SO  - Clin Chem. 2018 Mar;64(3):597-608. doi: 10.1373/clinchem.2017.278705. Epub 2017 
      Nov 14.