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Natriuretic Peptides and the Microcirkulation in Heart Failure Patients

Edvinsson, MarieLouise LU (2014) In Lund University Faculty of Medicine Doctoral Dissertation Series 2014:5.
Abstract
The increased prevalence of chronic congestive heart failure (HF) is a tremendous challenge for society. In spite of effective medical treatment for acute HF, better pharmacological treatment for specific neurohormonal intervention and better diagnostic tools, e.g. biomarkers of natriuretic peptides, the morbidity and mortality due to this disease are still prominent. HF leads to vascular dysfunction in the general circulation but the interpretation of this is not clear. In our studies we have focussed on defining endothelial and smooth muscle dysfunction in the microvasculature of HF patients and correlating this dysfunction with the disease state.

This thesis addresses studies of elderly patients with varying degrees of HF. We... (More)
The increased prevalence of chronic congestive heart failure (HF) is a tremendous challenge for society. In spite of effective medical treatment for acute HF, better pharmacological treatment for specific neurohormonal intervention and better diagnostic tools, e.g. biomarkers of natriuretic peptides, the morbidity and mortality due to this disease are still prominent. HF leads to vascular dysfunction in the general circulation but the interpretation of this is not clear. In our studies we have focussed on defining endothelial and smooth muscle dysfunction in the microvasculature of HF patients and correlating this dysfunction with the disease state.

This thesis addresses studies of elderly patients with varying degrees of HF. We determined blood levels of homocysteine and the natriuretic peptide precursor, NT-proBNP which is released by the failing heart. We also investigated vasoreactive response of the cutaneous microcirculation to different stimuli using a non-invasive iontophoresis-Laser Doppler probe method.

Paper I: We investigated the prognostic value of NT-proBNP for monitoring progression of HF. High blood levels (>5000) were found to indicate a poor prognosis of HF.

Paper II: An open study,- in which we evaluated the function of the cutaneous peripheral circulation of patients with chronic HF. We found that vasoreactivity declines with increasing age and HF.

Paper III: We evaluated vasoreactive responses in HF patients with homocysteinemi, before and 6 weeks after supplementary by B vitamin treatment. Homocysteine levels where then normalized and the cutaneous responses improved.

Paper IV: A controlled study in which, we investigated the microcirculation in chronic HF patients with different degrees of HF. We saw that the degree of severity of congestive HF did not correlate with decrease in vasoreactive responses.

Paper V: The effect of BNP in the microcirculation was studied in patients with severe congestive HF and compared to healthy, matched controls. The result shows that BNP has a significantly weaker vasodilation in HF patients and this is probably due to down regulation at the receptor-coupling level. (Less)
Abstract (Swedish)
Popular Abstract in Swedish

Forskningen har visat

Den ökade prevalensen av kronisk hjärtsvikt utgör en enorm utmaning för sjukvården. Trots att vi idag har effektiva medicinska behandlingar vid hjärtsvikt och bra läkemedel så är sjukligheten och dödligheten fortfarande betydande. Hjärtsvikt leder till en förändrad kärlreaktivitet generellt i cirkulationen, dock är betydelsen av denna endast känd i mindre omfattning.

Studierna har visat att blodkärlen på patienter med olika grad av hjärtsvikt har en generell kärldysfunktion.

Huvudfynden i avhandlingen är

1. Patienter med högt NT-proBNP (>5000) har en 50 % dödlighet inom 3 månader trots ” state - of- the- art” behandling. Mycket... (More)
Popular Abstract in Swedish

Forskningen har visat

Den ökade prevalensen av kronisk hjärtsvikt utgör en enorm utmaning för sjukvården. Trots att vi idag har effektiva medicinska behandlingar vid hjärtsvikt och bra läkemedel så är sjukligheten och dödligheten fortfarande betydande. Hjärtsvikt leder till en förändrad kärlreaktivitet generellt i cirkulationen, dock är betydelsen av denna endast känd i mindre omfattning.

Studierna har visat att blodkärlen på patienter med olika grad av hjärtsvikt har en generell kärldysfunktion.

Huvudfynden i avhandlingen är

1. Patienter med högt NT-proBNP (>5000) har en 50 % dödlighet inom 3 månader trots ” state - of- the- art” behandling. Mycket återstår att göra för denna patient grupp.

2. Hudens mikrocirkulation är reducerad hos hjärtsviktspatienter beroende på blodkärlsdysfunktion, ålder och grad av inflammation.

3. En något förbättrad kärlfunktion sågs efter behandling med inflammationsdämpande läkemedel i form av B-vitamin.

4. Grad av hjärtsvikt påverkade ej sänkningen av kärlreaktiviteten.

5. BNP hade dålig effekt som blodkärlsvidgare hos hjärtsviktspatienter troligen beroende på mättnad av receptorer i blodkärl eller reduktion av G-protein signalering. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • professor Boman, Kurt, Umeå Universitet
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Heart failure natriuretic peptides BNP cutaneous microcirculation
categories
Higher Education
in
Lund University Faculty of Medicine Doctoral Dissertation Series
volume
2014:5
pages
122 pages
publisher
Medicine (Lund)
defense location
Segerfalksalen, Sölvegatan 17, BMC, Lund
defense date
2014-02-21 13:00:00
ISSN
1652-8220
ISBN
978-91-87651-29-8
language
English
LU publication?
yes
id
8c7a3c0e-acad-46b3-9a53-60c95bac4555 (old id 4251370)
date added to LUP
2016-04-01 13:13:12
date last changed
2019-05-22 00:47:29
@phdthesis{8c7a3c0e-acad-46b3-9a53-60c95bac4555,
  abstract     = {{The increased prevalence of chronic congestive heart failure (HF) is a tremendous challenge for society. In spite of effective medical treatment for acute HF, better pharmacological treatment for specific neurohormonal intervention and better diagnostic tools, e.g. biomarkers of natriuretic peptides, the morbidity and mortality due to this disease are still prominent. HF leads to vascular dysfunction in the general circulation but the interpretation of this is not clear. In our studies we have focussed on defining endothelial and smooth muscle dysfunction in the microvasculature of HF patients and correlating this dysfunction with the disease state.<br/><br>
This thesis addresses studies of elderly patients with varying degrees of HF. We determined blood levels of homocysteine and the natriuretic peptide precursor, NT-proBNP which is released by the failing heart. We also investigated vasoreactive response of the cutaneous microcirculation to different stimuli using a non-invasive iontophoresis-Laser Doppler probe method.<br/><br>
Paper I: We investigated the prognostic value of NT-proBNP for monitoring progression of HF. High blood levels (&gt;5000) were found to indicate a poor prognosis of HF.<br/><br>
Paper II: An open study,- in which we evaluated the function of the cutaneous peripheral circulation of patients with chronic HF. We found that vasoreactivity declines with increasing age and HF. <br/><br>
Paper III: We evaluated vasoreactive responses in HF patients with homocysteinemi, before and 6 weeks after supplementary by B vitamin treatment. Homocysteine levels where then normalized and the cutaneous responses improved.<br/><br>
Paper IV: A controlled study in which, we investigated the microcirculation in chronic HF patients with different degrees of HF. We saw that the degree of severity of congestive HF did not correlate with decrease in vasoreactive responses. <br/><br>
Paper V: The effect of BNP in the microcirculation was studied in patients with severe congestive HF and compared to healthy, matched controls. The result shows that BNP has a significantly weaker vasodilation in HF patients and this is probably due to down regulation at the receptor-coupling level.}},
  author       = {{Edvinsson, MarieLouise}},
  isbn         = {{978-91-87651-29-8}},
  issn         = {{1652-8220}},
  keywords     = {{Heart failure natriuretic peptides BNP cutaneous microcirculation}},
  language     = {{eng}},
  publisher    = {{Medicine (Lund)}},
  school       = {{Lund University}},
  series       = {{Lund University Faculty of Medicine Doctoral Dissertation Series}},
  title        = {{Natriuretic Peptides and the Microcirkulation in Heart Failure Patients}},
  url          = {{https://lup.lub.lu.se/search/files/3237328/4251398.pdf}},
  volume       = {{2014:5}},
  year         = {{2014}},
}