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Natural history of markers of collagen turnover in patients with early diastolic dysfunction and impact of eplerenone.
Mak, George J Ledwidge, Mark T Watson, Chris J Phelan, Dermot M Dawkins, Ian R Murphy, Niamh F Patle, Anil K Baugh, John A McDonald, Kenneth M
Mak, George J
Ledwidge, Mark T
Watson, Chris J
Phelan, Dermot M
Dawkins, Ian R
Murphy, Niamh F
Patle, Anil K
Baugh, John A
McDonald, Kenneth M
Advisors
Editors
Other Contributors
Date
2012-02-01T10:29:29Z
Date Submitted
Keywords
Other Subjects
Subject Mesh
Aged
Aged, 80 and over
Aldosterone Antagonists/*administration & dosage
Biological Markers/blood
Collagen Type I/*blood
Collagen Type III/*blood
Echocardiography, Doppler
Female
Follow-Up Studies
Heart Failure, Diastolic/*blood/drug therapy/physiopathology
Heart Ventricles/*physiopathology/ultrasonography
Humans
Male
Procollagen/*blood
Prospective Studies
Radioimmunoassay
Spironolactone/administration & dosage/*analogs & derivatives
Treatment Outcome
Aged, 80 and over
Aldosterone Antagonists/*administration & dosage
Biological Markers/blood
Collagen Type I/*blood
Collagen Type III/*blood
Echocardiography, Doppler
Female
Follow-Up Studies
Heart Failure, Diastolic/*blood/drug therapy/physiopathology
Heart Ventricles/*physiopathology/ultrasonography
Humans
Male
Procollagen/*blood
Prospective Studies
Radioimmunoassay
Spironolactone/administration & dosage/*analogs & derivatives
Treatment Outcome
Planned Date
Start Date
Collaborators
Principal Investigators
Alternative Titles
Publisher
Abstract
OBJECTIVES: This study was designed to evaluate the impact of eplerenone on collagen turnover in preserved systolic function heart failure (HFPSF). BACKGROUND: Despite growing interest in abnormal collagen metabolism as a feature of HFPSF with diastolic dysfunction, the natural history of markers of collagen turnover and the impact of selective aldosterone antagonism on this natural history remains unknown. METHODS: We evaluated 44 patients with HFPSF, randomly assigned to control (n = 20) or eplerenone 25 mg daily (n = 24) for 6 months, increased to 50 mg daily from 6 to 12 months. Serum markers of collagen turnover and inflammation were analyzed at baseline and at 6 and 12 months and included pro-collagen type-I and -III aminoterminal peptides, matrix metalloproteinase type-2, interleukin-6 and -8, and tumor necrosis factor-alpha. Doppler-echocardiographic assessment of diastolic filling indexes and tissue Doppler analyses were also obtained. RESULTS: The mean age of the patients was 80 +/- 7.8 years; 46% were male; 64% were receiving an angiotensin-converting enzyme inhibitor, 34% an angiotensin-II receptor blocker, and 68% were receiving beta-blocker therapy. Pro-collagen type-III and -I aminoterminal peptides, matrix metalloproteinase type-2, interleukin-6 and -8, and tumor necrosis factor-alpha increased with time in the control group. Eplerenone treatment had no significant impact on any biomarker at 6 months but attenuated the increase in pro-collagen type-III aminoterminal peptide at 12 months (p = 0.006). Eplerenone therapy was associated with modest effects on diastolic function without any impact on clinical variables or brain natriuretic peptide. CONCLUSIONS: This study demonstrates progressive increases in markers of collagen turnover and inflammation in HFPSF with diastolic dysfunction. Despite high background utilization of renin-angiotensin-aldosterone modulators, eplerenone therapy prevents a progressive increase in pro-collagen type-III aminoterminal peptide and may have a role in management of this disease. (The Effect of Eplerenone and Atorvastatin on Markers of Collagen Turnover in Diastolic Heart Failure; NCT00505336).
Language
eng
ISSN
1558-3597 (Electronic)
0735-1097 (Linking)
0735-1097 (Linking)
eISSN
ISBN
DOI
10.1016/j.jacc.2009.08.021
PMID
19850207