Published Online
on May 14, 2009

A more recent version of this article appeared on July 1, 2009

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Original Article

The Association Between Elevated Fibrosis Markers and Heart Failure in the Elderly: The Cardiovascular Health Study

Eddy Barasch^1,6; John S. Gottdiener²; Gerard Aurigemma³; Dalane W. Kitzman⁴; Jing Han¹; Willem J. Kop² and Russell P. Tracy⁵

¹ St. Francis Hospital/SUNY at Stony Brook, Roslyn, NY;
² The University of Maryland Medical Systems, Baltimore, MD;
³ The University of Massachusetts, Worcester, MA;
⁴ The Wake Forest University, Winston-Salem, NC;
⁵ The University of Vermont, Burlington, VT

⁶ E-mail: eddy.barasch{at}chsli.org

Background—Myocardial fibrosis reflects excess collagen deposition in the extracellular left ventricular (LV) 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 yrs, 48% female). Participants with systolic HF (n=179, LV ejection fraction < 55%) and those with diastolic HF (n=131, LV ejection fraction 55%) were compared to 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 (PIP), carboxyl-terminal telopeptide of collagen type I (CITP), and amino-terminal peptide of procollagen type III (PIIINP). Echocardiography was used to document systolic and diastolic function parameters. Analysis of variance and logistic regression (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 ACE inhibitor, spironolactone or any diuretic, NT-proBNP and total bone mineral density were performed.

Systolic HF was associated with significantly elevated CITP (OR = 2.6; 95%CI = 1.2-5.7) and PIIINP (OR = 3.3; 95% CI = 1.6 -5.8), when adjusting for covariates. Associations of diastolic HF were significant for CITP (OR = 3.9, 95% CI = 1.9-8.3) and PIIINP (OR = 2.7; 95% CI = 1.4-5.4). HF was not associated with elevated PIP (p > 0.10), and fibrosis markers did not significantly differ between HF with diastolic versus those with systolic dysfunction (p values > 0.10) whereas NT- proBNP mean values were higher in SHF than in DHF (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: collagen • heart failure • population

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