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 multi-marker analysis may help identify distinct subgroups of patients who respond to exercise. The primary study objective was to identify common and distinct patterns of change in hsCRP and NT-proBNP and 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 sub-study 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 NTproBNP and hsCRP were identified. Two patterns were combined and compared to 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, had hypertension or ischemic etiology were about two 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, CI: 0.32–0.98, p=0.04). 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.

Effect of exercise therapy on established and emerging circulating biomarkers in patients with heart failure: a systematic review and meta-analysis

“…Biomarkers are used in HF clinical trials for a number of reasons,10 including establishment of inclusion criteria, outcome measures, explaining therapeutic efficacy and as a target for therapy 93. Biomarkers and biomarker panels may aid in identifying subgroups of patients with HF who may have a more favourable response to exercise therapy, distinguishing responders and non-responders21 23 in terms of specified outcomes including functional and long-term outcomes. Different biomarkers may provide further insight into the downstream molecular mechanisms associated with improvements from exercise training 21.…”

“…In addition to their diagnostic and prognostic utility, biomarker profiles may prove beneficial in guiding HF therapy and improving treatment strategies,10 including the identification of patients with HF that may respond to exercise training 21–23. A 2010 meta-analysis24 suggested that exercise training had a favourable effect on both BNP and NT-proBNP.…”

Inflammatory biomarkers and effect of exercise on functional capacity in patients with heart failure: Insights from a randomized clinical trial

“…Another sub-analysis from the HF-ACTION study showed an association of elevated or worsening high-sensitivity C-reactive protein and N-terminal pro-B-type natriuretic peptide blood levels with lower peak _ VO 2 over time. 28 We clarify for the first time that the response to exercise is associated with blood levels of other biomarkers associated with proinflammatory processes, IL-6 and TNF-alpha.…”

“…[26][27][28] In the HF-ACTION study, patients with heart failure were classified through cluster analysis in four different phenotypes that differed from each other regarding their overall prognosis and the effect of exercise on cardiovascular mortality and heart failure hospitalization. 27 The patients in the phenotype that displayed the largest peak _ VO 2 improvement with three-month exercise were the youngest, mainly had heart failure from non-ischemic causes and apparently less advanced heart failure, as reflected by low _ VE-_ VCO 2 slope in the CPET and low blood levels of galectin-3, in concordance with our findings.…”

Exercise and heart failure: Improve your functional status and your biomarker profile

“…2 On the other hand, evidence in favour of (cardiovascular) exercise is mounting, and has already been incorporated into a World Health Organization statement and in the International Society and Federation of Cardiology position paper of 1994. 3 However, despite striking effects on exercise performance, on slowing disease progression, 4 on improving symptoms, 5 quality of life and outcomes 6 of chronic heart failure (CHF) patients, 7 the effects on biomarker levels are less clear.…”