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

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    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.
    Issue Date
    2012-02-01T10:29:29Z
    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
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    Citation
    J Am Coll Cardiol. 2009 Oct 27;54(18):1674-82.
    Journal
    Journal of the American College of Cardiology
    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
    ISSN
    1558-3597 (Electronic)
    0735-1097 (Linking)
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.jacc.2009.08.021
    Scopus Count
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    St. Vincent's University Hospital

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