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

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).

• Authors: George J Mak, Mark T Ledwidge, Chris J Watson, Dermot M Phelan, Ian R Dawkins, Niamh F Murphy, Anil K Patle, John A Baugh, Kenneth M McDonald
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 54 Issue 18 Pg. 1674-82 (Oct 27 2009) ISSN: 1558-3597 [Electronic] United States
• PMID: 19850207 (Publication Type: Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Collagen Type I
• Collagen Type III
• Mineralocorticoid Receptor Antagonists
• Procollagen
• Spironolactone
• Eplerenone

Topics

• Aged
• Aged, 80 and over
• Biomarkers (blood)
• Collagen Type I (blood)
• Collagen Type III (blood)
• Echocardiography, Doppler
• Eplerenone
• Female
• Follow-Up Studies
• Heart Failure, Diastolic (blood, drug therapy, physiopathology)
• Heart Ventricles (diagnostic imaging, physiopathology)
• Humans
• Male
• Mineralocorticoid Receptor Antagonists (administration & dosage)
• Procollagen (blood)
• Prospective Studies
• Radioimmunoassay
• Spironolactone (administration & dosage, analogs & derivatives)
• Treatment Outcome