Identifying biomarker patterns and predictors of inflammation and myocardial stress

Abstract

Background: Regular exercise is recommended to improve outcomes in patients with heart failure. Exercise is known to decrease inflammation and thought to decrease myocardial stress; however, studies of exercise in heart failure have had mixed results on levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hsCRP). A multimarker analysis may help to identify distinct subgroups of patients who respond to exercise. Our primary study objective was to identify common and distinct patterns of change in hsCRP and NT-proBNP and to quantify the influence of exercise therapy on the observed patterns of change.

Methods and results: NT-proBNP and hsCRP were assessed in a random sample of 320 participants from the biomarker substudy of HF-ACTION, a randomized clinical trial of exercise training versus usual care in patients with stable and chronic heart failure. Growth mixture modeling was used to identify unique biomarker patterns over 12 months. Three statistically independent and clinically meaningful biomarker patterns of NT-proBNP and hsCRP were identified. Two patterns were combined and compared with the "low/stable" pattern, which was characterized by the lowest levels of NT-proBNP and hsCRP over time. Participants who were taking a loop diuretic and had hypertension or ischemic etiology were ∼2 times as likely to be in the "elevated/worsening" biomarker pattern. Participants randomized to the exercise intervention were less likely to be in the elevated/worsening pattern of NT-proBNP and hsCRP (relative risk ratio 0.56, 95% confidence interval 0.32-0.98; P = .04).

Conclusions: Exercise therapy was protective for reducing the frequency of membership in the elevated/worsening biomarker pattern, indicating that exercise may be helpful in delaying the progression of heart failure.

Keywords: Heart failure; biological markers; exercise therapy; inflammation.

Copyright © 2015 Elsevier Inc. All rights reserved.

Figures

Figure 1

This figure reports no statistically significant change in mean ln(NT-proBNP) and ln(hsCRP) between baseline and 12-months with 95% confidence intervals over time between the usual care and exercise training groups. P-values reported are from ANCOVA models adjusted for baseline biomarker values and treatment allocation.

Figure 2

Three statistically independent and clinically meaningful biomarker patterns of ln(NTproBNP) and ln(hsCRP) are presented. Patterns 1 and 3 were combined and labeled “elevated/worsening” and compared to Pattern 2, labeled “low/stable.” For economy of presentation, error bars were not included in this figure.

Figure 3

Differences in changes in peak oxygen consumption are presented comparing elevated/worsening (dotted line) and low/stable (solid line) patterns. Differences in the intercept (i) indicate that baseline values of peak oxygen consumption were higher in the low/stable pattern at baseline relative to the elevated/worsening pattern. Differences in the slope (s) indicate that the change over time was statistically significant (p=0.020) comparing the elevated/worsening and low/stable patterns over one-year.