Potential spironolactone effects on collagen metabolism biomarkers in patients with uncontrolled blood pressure.
Aged
Biological Availability
Biomarkers
/ blood
Blood Pressure
/ drug effects
Collagen
/ biosynthesis
Drug Monitoring
/ methods
Drug Resistance
Female
Heart Failure
/ etiology
Humans
Hypertension
/ complications
Male
Middle Aged
Mineralocorticoid Receptor Antagonists
/ administration & dosage
Outcome Assessment, Health Care
Peptide Fragments
/ blood
Procollagen
/ blood
Spironolactone
/ administration & dosage
heart failure
hypertension
Journal
Heart (British Cardiac Society)
ISSN: 1468-201X
Titre abrégé: Heart
Pays: England
ID NLM: 9602087
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
21
02
2018
revised:
21
07
2018
accepted:
26
07
2018
pubmed:
20
8
2018
medline:
8
5
2020
entrez:
20
8
2018
Statut:
ppublish
Résumé
An increase in myocardial collagen content may contribute to the development of heart failure; this might be inhibited or reversed by mineralocorticoid receptor antagonists (MRAs). We investigated changes in serum concentrations of the collagen synthesis biomarkers N-terminal propeptide of procollagen type III (PIIINP) (primary outcome) and C-terminal propeptide of procollagen type I (PICP) (secondary outcome) after non-randomised initiation of spironolactone as add-on therapy among patients with resistant hypertension enrolled in the 'Anglo-Scandinavian Cardiac Outcomes' trial (ASCOT). An age/sex matching plus propensity-scored logistic regression model incorporating variables related to the outcome and spironolactone treatment was created to compare patients treated with spironolactone for a 9-month period versus matched controls. A within-person analysis comparing changes in serum biomarker concentrations in the 9 months before versus after spironolactone treatment was also performed. Patients included in the between-person analysis (n=146) were well matched: the mean age was 63±7 years and 11% were woman. Serum concentrations of PIIINP and PICP rose in 'controls' and fell during spironolactone treatment (adjusted means +0.52 (-0.05 to 1.09) vs -0.41 (-0.97 to 0.16) ng/mL, p=0.031 for PIIINP and +4.54(-1.77 to 10.9) vs -6.36 (-12.5 to -0.21) ng/mL, p=0.023 for PICP). For the within-person analysis (n=173), spironolactone treatment was also associated with a reduction in PICP (beta estimate=-11.82(-17.53 to -6.10) ng/mL, p<0.001) but not in PIIINP levels. Treatment with spironolactone was associated with a reduction in serum biomarkers of collagen synthesis independently of blood pressure in patients with hypertension, suggesting that spironolactone might exert favourable effects on myocardial collagen synthesis and fibrosis. Whether this effect might contribute to slowing the progression to heart failure is worth investigating.
Sections du résumé
BACKGROUND
An increase in myocardial collagen content may contribute to the development of heart failure; this might be inhibited or reversed by mineralocorticoid receptor antagonists (MRAs). We investigated changes in serum concentrations of the collagen synthesis biomarkers N-terminal propeptide of procollagen type III (PIIINP) (primary outcome) and C-terminal propeptide of procollagen type I (PICP) (secondary outcome) after non-randomised initiation of spironolactone as add-on therapy among patients with resistant hypertension enrolled in the 'Anglo-Scandinavian Cardiac Outcomes' trial (ASCOT).
METHODS
An age/sex matching plus propensity-scored logistic regression model incorporating variables related to the outcome and spironolactone treatment was created to compare patients treated with spironolactone for a 9-month period versus matched controls. A within-person analysis comparing changes in serum biomarker concentrations in the 9 months before versus after spironolactone treatment was also performed.
RESULTS
Patients included in the between-person analysis (n=146) were well matched: the mean age was 63±7 years and 11% were woman. Serum concentrations of PIIINP and PICP rose in 'controls' and fell during spironolactone treatment (adjusted means +0.52 (-0.05 to 1.09) vs -0.41 (-0.97 to 0.16) ng/mL, p=0.031 for PIIINP and +4.54(-1.77 to 10.9) vs -6.36 (-12.5 to -0.21) ng/mL, p=0.023 for PICP). For the within-person analysis (n=173), spironolactone treatment was also associated with a reduction in PICP (beta estimate=-11.82(-17.53 to -6.10) ng/mL, p<0.001) but not in PIIINP levels.
CONCLUSIONS
Treatment with spironolactone was associated with a reduction in serum biomarkers of collagen synthesis independently of blood pressure in patients with hypertension, suggesting that spironolactone might exert favourable effects on myocardial collagen synthesis and fibrosis. Whether this effect might contribute to slowing the progression to heart failure is worth investigating.
Identifiants
pubmed: 30121630
pii: heartjnl-2018-313182
doi: 10.1136/heartjnl-2018-313182
doi:
Substances chimiques
Biomarkers
0
Mineralocorticoid Receptor Antagonists
0
Peptide Fragments
0
Procollagen
0
procollagen Type III-N-terminal peptide
0
procollagen type I carboxy terminal peptide
0
Spironolactone
27O7W4T232
Collagen
9007-34-5
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
307-314Informations de copyright
© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.
Déclaration de conflit d'intérêts
Competing interests: None declared.