Published online before print May 14, 2009, doi: 10.1161/CIRCHEARTFAILURE.108.828343
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Original Articles |
Association Between Elevated Fibrosis Markers and Heart Failure in the Elderly
The Cardiovascular Health Study
From the Department of Research and Education, St Francis Hospital/SUNY at Stony Brook (E.B., J.H.), Roslyn, NY; Department of Internal Medicine, Division of Cardiology, the University of Maryland Medical Systems (J.S.G., W.J.K.), Baltimore, Md; Department of Internal Medicine, Division of Cardiology, University of Massachusetts (G.A.), Worcester, Mass; Department of Internal Medicine, Division of Cardiology, Wake Forest University (D.W.K.), Winston-Salem, NC; and Laboratory of Clinical Biochemistry Research, University of Vermont (R.P.T.), Burlington, Vt.
Correspondence to Eddy Barasch, MD, Department of Research and Education, St Francis Hospital, Roslyn, NY 11576. E-mail eddy.barasch{at}chsli.org
Received October 16, 2008; accepted April 23, 2009.
Background— Myocardial fibrosis reflects excess collagen deposition in the extracellular left ventricular matrix, which has been associated with heart failure (HF). No studies have addressed the relation between fibrosis biomarkers and HF in the elderly.
Methods and Results— Serum fibrosis markers were measured in 880 participants of the Cardiovascular Health Study (mean age 77±6 years, 48% women). Participants with systolic HF (n=131, left ventricular ejection fraction <55%) and those with diastolic HF (n=179, left ventricular ejection fraction 
55%) were compared with controls (280 with cardiovascular risk factors, and 279 healthy individuals) using a nested case-control design. Fibrosis markers included carboxyl-terminal peptide of procollagen type I, carboxyl-terminal telopeptide of collagen type I, and amino-terminal peptide of procollagen type III. Echocardiography was used to document systolic and diastolic function parameters. Analysis of variance and logistic regression analysis (per tertile odds ratios [OR]), adjusted by age, gender, race, hypertension, atrial fibrillation, coronary heart disease, baseline serum glucose, serum cystatin C, serum creatinine, C-reactive protein, any angiotensin-converting enzyme inhibitor, spironolactone or any diuretic, NT-proBNP, and total bone mineral density were performed. Systolic HF was associated with significantly elevated carboxyl-terminal telopeptide of collagen type I (OR=2.6; 95% CI=1.2 to 5.7) and amino-terminal peptide of procollagen type III (OR=3.3; 95% CI=1.6 to 5.8), when adjusting for covariates. Associations of diastolic HF were significant for carboxyl-terminal telopeptide of collagen type I (OR=3.9; 95% CI=1.9 to 8.3) and amino-terminal peptide of procollagen type III (OR=2.7; 95% CI=1.4 to 5.4). HF was not associated with elevated carboxyl-terminal peptide of procollagen type I (P>0.10), and fibrosis markers did not significantly differ between HF with diastolic versus those with systolic dysfunction (P>0.10) whereas NT-proBNP mean values were higher in systolic heart failure than in diastolic heart failure (P<0.0001).
Conclusions— Fibrosis markers are significantly elevated in elderly individuals with diastolic or systolic HF. These associations remained significant when adjusting for covariates relevant to the aging process.
Key Words: heart failure • collagen • population
CLINICAL PERSPECTIVE
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