Association between elevated fibrosis markers and heart failure in the elderly: the cardiovascular health study

Abstract

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 > or =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.

Figure 1

The Median Values and Interquartile Range of PIP. No differences have been found between the 4 groups.

Figure 2

The Median Values and Interquartile Range of CITP. Significant differences have been found between: a) healthy control group and diastolic HF, systolic HF and control group (p<0.0001, p<0.0001, and p=0.0006, respectively); b) control group and diastolic HF and systolic HF (p<0.0001 for both).

Figure 3

The Median Values and Interquartile Range of PIIINP. Significant differences have been found between: a) healthy control group and diastolic HF, systolic HF and control (p<0.0001 for all three); b) control group and diastolic HF and systolic HF ( p=0.0008 and p<0.0001, respectively). In the Box-and-whisker plot, the central box represents the values from the lower to upper quartile (25 to 75 percentile). The middle line represents the median. The horizontal line extends from the minimum to the maximum value, excluding outside and far out values which are displayed as separate points.