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Relation of Peripheral Collagen Markers to Death and Hospitalisation in Patients with Heart Failure and Preserved Ejection Fraction: Results of the I-PRESERVE Collagen Sub-Study.
MedLine Citation:
PMID:  21750125     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: -Heart failure with preserved ejection fraction (HFPEF) is a common and increasing public health problem. Myocardial fibrosis is a key pathological feature of HFPEF. Peripheral collagen markers may reflect this excess fibrosis; however, the relation of these markers to prognosis in HFPEF patients has not as yet been determined. METHODS AND RESULTS: -This sub-study of I-PRESERVE measured plasma levels of procollagen type I amino-terminal peptide (PINP), PIIINP and osteopontin in 313 patients with HFPEF. Measurements were performed at baseline and six months following randomisation to placebo or irbesartan 300mg/day. The relation of baseline collagen markers to the I-PRESERVE primary endpoint (all-cause death and hospitalisation for prespecified cardiovascular causes) was evaluated by single and multivariable analysis. Similar evaluations were performed for all-cause death alone as well as heart failure events (death or hospitalization due to heart failure). Increased plasma levels of collagen markers at baseline were associated with increased frequency of the study primary endpoint for all collagen markers. For each 10μg/L increase in PINP, the hazard ratio (HR) for the primary endpoint was 1.09, 95% CI (1.052-1.13) p<0.0001; for 10μg/L increase in PIIINP the HR was 2.47 (0.97-6.33) p=0.059; for each 10 nmol/L increase in osteopontin, the HR was 1.084 (1.026-1.15), p=0.004. No variable remained significant as an independent predictor when introduced into a multivariable model. Both treatment groups tended to reduce collagen markers, with the reduction significantly greater for placebo versus irbesartan for PIIINP only, p=0.0185. CONCLUSIONS: -Increased peripheral collagen turnover markers were not independently associated with increased mortality and cardiovascular hospitalisation in a HFPEF population on multivariable analysis, but were associated on single variable analysis. These findings provide some support to the hypothesis that pathological fibrosis in the heart, and possibly the peripheral vasculature, may be contributory to adverse clinical outcomes in HFPEF patients. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00095238.
Authors:
Henry Krum; Maros Elsik; Hans G Schneider; Agata Ptaszynska; Marion Black; Peter E Carson; Michel Komajda; Barry M Massie; Robert McKelvie; John J McMurray; Michael R Zile; Inder Anand
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-7-12
Journal Detail:
Title:  Circulation. Heart failure     Volume:  -     ISSN:  1941-3297     ISO Abbreviation:  -     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-7-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101479941     Medline TA:  Circ Heart Fail     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1 CCRE Therapeutics, Monash University, Melbourne, Australia;
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