Title | The relationship between serum markers of collagen turnover and cardiovascular outcome in the elderly: the Cardiovascular Health Study. |
Publication Type | Journal Article |
Year of Publication | 2011 |
Authors | Barasch, E, Gottdiener, JS, Aurigemma, G, Kitzman, DW, Han, J, Kop, WJ, Tracy, RP |
Journal | Circ Heart Fail |
Volume | 4 |
Issue | 6 |
Pagination | 733-9 |
Date Published | 2011 Nov |
ISSN | 1941-3297 |
Keywords | Aged, Aged, 80 and over, Aging, Biomarkers, Cardiovascular Diseases, Case-Control Studies, Cohort Studies, Collagen, Collagen Type I, Female, Follow-Up Studies, Heart Failure, Humans, Incidence, Male, Peptide Fragments, Peptides, Predictive Value of Tests, Procollagen, Prospective Studies, Stroke Volume, Survival Rate |
Abstract | <p><b>BACKGROUND: </b>The deposition of collagen fibrils in the myocardial extracellular matrix increases with age and plays a key role in the pathophysiology of heart failure (HF). We sought to determine the predictive value of serum markers of collagen turnover for incident HF and cardiovascular (CV) morbidity, mortality, and all-cause mortality in elderly individuals.</p><p><b>METHODS AND RESULTS: </b>In 880 participants in the Cardiovascular Health Study (mean age, 77±6 years; 48% women), serum levels of carboxyl-terminal peptide of procollagen type I (PIP), carboxyl-terminal telopeptide of collagen type I (CITP), and amino-terminal peptide of procollagen type III (PIIINP) were measured in 4 groups: HF with reduced ejection fraction (HFREF; n=146, EF <55%); HF with preserved EF (HFPEF; n=175, EF ≥55%), control subjects with CV risk factors but not HF (CVD; n=280), and healthy control subjects free of CV disease (n=279). Relationships between these serum markers and outcome at follow-up of 12±4 years (range, 3-17 years) was determined in six models including those adjusted for conventional risk factors, renal function, NT-proBNP and agents which interfere with collagen synthesis. For the entire cohort, in unadjusted and adjusted models, both PIIINP and CITP were associated with myocardial infarction, incident HF, hospitalization for HF, cardiovascular and all-cause mortality. In healthy control subjects, CITP and PIIINP were associated with all-cause death. In control subjects with risk factors, CITP was associated with incident HF, and in participants with HFPEF, CITP was associated with hospitalization for HF. No collagen biomarker was associated with outcome in participants with HFREF, and PIP was not associated with outcome in the cohort or its subgroups.</p><p><b>CONCLUSIONS: </b>In both healthy and elderly individuals with CV disease at risk of developing HF, CITP and PIIINP are significantly associated with multiple adverse cardiac outcomes including myocardial infarction, HF, and death. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00005133.</p> |
DOI | 10.1161/CIRCHEARTFAILURE.111.962027 |
Alternate Journal | Circ Heart Fail |
PubMed ID | 21900186 |
PubMed Central ID | PMC3263368 |
Grant List | R03AG23291 / AG / NIA NIH HHS / United States T32 HL007902 / HL / NHLBI NIH HHS / United States P30 AG024827 / AG / NIA NIH HHS / United States R01 AG-15928 / AG / NIA NIH HHS / United States 1-T32-HL07902 / HL / NHLBI NIH HHS / United States P50 HL015103 / HL / NHLBI NIH HHS / United States N01-HC85079 / HC / NHLBI NIH HHS / United States R01 AG015928 / AG / NIA NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States R37AG18915 / AG / NIA NIH HHS / United States R37 AG018915 / AG / NIA NIH HHS / United States R01 AG018915 / AG / NIA NIH HHS / United States P30-AG-024827 / AG / NIA NIH HHS / United States AG09556 / AG / NIA NIH HHS / United States R01 HL-0753 / HL / NHLBI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States RC-HL15103 / HL / NHLBI NIH HHS / United States R03 AG023291-01A1 / AG / NIA NIH HHS / United States AG-027058 / AG / NIA NIH HHS / United States RC-HL35129 / HL / NHLBI NIH HHS / United States N01-HC80007 / HC / NHLBI NIH HHS / United States N01-HC-55222 / HC / NHLBI NIH HHS / United States N01-HC 35129 / HC / NHLBI NIH HHS / United States R01 AG-20098 / AG / NIA NIH HHS / United States R03 AG023291 / AG / NIA NIH HHS / United States R01 AG020098 / AG / NIA NIH HHS / United States R01 HL043201 / HL / NHLBI NIH HHS / United States HL43201 / HL / NHLBI NIH HHS / United States N01-HC-8086 / HC / NHLBI NIH HHS / United States R01 AG009556 / AG / NIA NIH HHS / United States AG-023629 / AG / NIA NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States R01 AG027058 / AG / NIA NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States N01-HC-75170 / HC / NHLBI NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States R56 AG023629 / AG / NIA NIH HHS / United States |