Natural history of markers of collagen turnover in patients with early diastolic dysfunction and impact of eplerenone.

Hdl Handle:
http://hdl.handle.net/10147/207496
Title:
Natural history of markers of collagen turnover in patients with early diastolic dysfunction and impact of eplerenone.
Authors:
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
Affiliation:
St. Vincent's University Hospital, Dublin, Ireland.
Citation:
J Am Coll Cardiol. 2009 Oct 27;54(18):1674-82.
Journal:
Journal of the American College of Cardiology
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207496
DOI:
10.1016/j.jacc.2009.08.021
PubMed ID:
19850207
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
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
ISSN:
1558-3597 (Electronic); 0735-1097 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorMak, George Jen_GB
dc.contributor.authorLedwidge, Mark Ten_GB
dc.contributor.authorWatson, Chris Jen_GB
dc.contributor.authorPhelan, Dermot Men_GB
dc.contributor.authorDawkins, Ian Ren_GB
dc.contributor.authorMurphy, Niamh Fen_GB
dc.contributor.authorPatle, Anil Ken_GB
dc.contributor.authorBaugh, John Aen_GB
dc.contributor.authorMcDonald, Kenneth Men_GB
dc.date.accessioned2012-02-01T10:29:29Z-
dc.date.available2012-02-01T10:29:29Z-
dc.date.issued2012-02-01T10:29:29Z-
dc.identifier.citationJ Am Coll Cardiol. 2009 Oct 27;54(18):1674-82.en_GB
dc.identifier.issn1558-3597 (Electronic)en_GB
dc.identifier.issn0735-1097 (Linking)en_GB
dc.identifier.pmid19850207en_GB
dc.identifier.doi10.1016/j.jacc.2009.08.021en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207496-
dc.description.abstractOBJECTIVES: 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).en_GB
dc.language.isoengen_GB
dc.subject.meshAgeden_GB
dc.subject.meshAged, 80 and overen_GB
dc.subject.meshAldosterone Antagonists/*administration & dosageen_GB
dc.subject.meshBiological Markers/blooden_GB
dc.subject.meshCollagen Type I/*blooden_GB
dc.subject.meshCollagen Type III/*blooden_GB
dc.subject.meshEchocardiography, Doppleren_GB
dc.subject.meshFemaleen_GB
dc.subject.meshFollow-Up Studiesen_GB
dc.subject.meshHeart Failure, Diastolic/*blood/drug therapy/physiopathologyen_GB
dc.subject.meshHeart Ventricles/*physiopathology/ultrasonographyen_GB
dc.subject.meshHumansen_GB
dc.subject.meshMaleen_GB
dc.subject.meshProcollagen/*blooden_GB
dc.subject.meshProspective Studiesen_GB
dc.subject.meshRadioimmunoassayen_GB
dc.subject.meshSpironolactone/administration & dosage/*analogs & derivativesen_GB
dc.subject.meshTreatment Outcomeen_GB
dc.titleNatural history of markers of collagen turnover in patients with early diastolic dysfunction and impact of eplerenone.en_GB
dc.contributor.departmentSt. Vincent's University Hospital, Dublin, Ireland.en_GB
dc.identifier.journalJournal of the American College of Cardiologyen_GB
dc.description.provinceLeinster-

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