Elsevier

American Heart Journal

Volume 167, Issue 2, February 2014, Pages 193-202.e1
American Heart Journal

Clinical Investigation
Heart Failure
The effects of exercise on cardiovascular biomarkers in patients with chronic heart failure

https://doi.org/10.1016/j.ahj.2013.10.018Get rights and content

Background

Exercise training is recommended for chronic heart failure (HF) patients to improve functional status and reduce risk of adverse outcomes. Elevated plasma levels of amino-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), and cardiac troponin T (cTnT) are associated with increased risk of adverse outcomes in this patient population. Whether exercise training leads to improvements in biomarkers and how such improvements relate to clinical outcomes are unclear.

Methods and Results

Amino-terminal pro-brain natriuretic peptide, hs-CRP, and cTnT levels were assessed at baseline and 3 months in a cohort of 928 subjects from the HF-ACTION study, a randomized clinical trial of exercise training versus usual care in chronic HF patients with reduced left ventricular ejection fraction (<35%). Linear and logistic regressions were used to assess 3-month biomarker levels as a function of baseline value, treatment assignment (exercise training vs usual care), and volume of exercise. Linear regression and Cox proportional hazard modeling were used to evaluate the relations between changes in biomarker levels and clinical outcomes of interest that included change in peak oxygen consumption (peak VO2), hospitalizations, and mortality. Exercise training was not associated with significant changes in levels of NT-proBNP (P = .10), hs-CRP (P = .80), or detectable cTnT levels (P = .83) at 3 months. Controlling for baseline biomarker levels or volume of exercise did not alter these findings. Decreases in plasma concentrations of NT-proBNP, but not hs-CRP or cTnT, were associated with increases in peak VO2 (P < .001) at 3 months and decreased risk of hospitalizations or mortality (P ≤ .04), even after adjustment for a comprehensive set of known predictors.

Conclusions

Exercise training did not lead to meaningful changes in biomarkers of myocardial stress, inflammation, or necrosis in patients with chronic HF. Only improvements in NT-proBNP translated to reductions in peak VO2 and reduced risk of clinical events.

Section snippets

Study population

Details of the design, rationale, and primary results of the HF-ACTION study have been published elsewhere.6., 7. Briefly, HF-ACTION (clinicaltrials.gov: NCT00047437) was a randomized clinical trial evaluating the effect of exercise training versus usual care on long-term morbidity and mortality in 2,331 patients with chronic HF due to left ventricular systolic dysfunction (New York Heart Association [NYHA] classes II-IV, left ventricular ejection fraction [LVEF] <35%).

Exercise testing

Patients were randomized

Baseline characteristics

Baseline and 3-month plasma levels of NT-proBNP, hs-CRP, and cTnT were available for 928 patients, who were broadly similar to the HF-ACTION cohort as a whole (n = 2,331, online Appendix Supplementary Table I). Patient characteristics of this cohort, as a whole and according to randomization group, are shown in Table I. Median age of the study cohort was 59 years; of these, 63% were white, and 71% were male. Most patients were NYHA class II (67%) or NYHA class III (32%) at study onset, and

Discussion

Findings from this study challenge the hypothesis that exercise training improves commonly evaluated cardiovascular biomarkers in patients with chronic HF. We found that plasma levels of NT-proBNP, hs-CRP, or cTnT did not significantly improve at 3 months despite a structured exercise training program, even after accounting for baseline biomarker levels. Although patients who tended to exercise more had lower levels of NT-proBNP and hs-CRP and decreased risk of adverse clinic outcomes, volume

Disclosures

Drs Felker, Fiuzat, and O'Connor have received research funding from BG Medicine, Critical Diagnostics, and Roche Diagnostics. Drs Felker and O'Connor have served as consultants for Roche Diagnostics. Dr Zannad has received research funding from BG Medicine and Roche Diagnostics and served as a consultant for BG Medicine. Dr Kitzman serves as a consultant for Relypsa, Inc. None of the other authors report any conflicts.

References (30)

Cited by (49)

  • Meta-Analysis of Physical Training on Natriuretic Peptides and Inflammation in Heart Failure

    2022, American Journal of Cardiology
    Citation Excerpt :

    The most prevalent co-morbidities were hypertension and diabetes mellitus. A total of 8 trials11,15,18,21,30,32,41,43 included patients receiving cardiac resynchronization therapy. Most studies reported data on clinical stability or optimal pharmacological therapy before enrollment in the protocols, which ranged from 4 weeks to more than 12 months.

  • The role of exercise training on cardiovascular peptides in patients with heart failure: A systematic review and meta-analysis

    2022, Current Research in Physiology
    Citation Excerpt :

    The characteristics of exercise training interventions and control group-related interventions are illustrated in Table 3. Types of exercise interventions including aerobic (Abolahrari-Shirazi et al., 2018; Ahmad et al., 2014; Aksoy et al., 2015; Conraads et al., 2007; Eleuteri et al., 2013; Fu et al., 2013; Giallauria et al., 2006-a; Giallauria et al., 2006-b; Giallauria et al., 2008; Kobayashi et al., 2003; Maria-Sarullo et al., 2006; Masterson-Creber et al., 2015; Melo et al., 2019; Nilsson et al., 2010; Passino et al., 2006; Radi et al., 2017; Sandri et al., 2012; Wisløff et al., 2007; Yeh et al., 2004; Yeh et al., 2011), resistance (Karavidas et al., 2008; Kawauchi et al., 2017), and concurrent (Abolahrari-Shirazi et al., 2018; Adamopoulos et al., 2014; Conraads et al., 2004; Delagardelle et al., 2008; Marco et al., 2013; Prescott et al., 2009; Van Berendoncks et al., 2010) were studies included in our meta-analysis. The intensity ranges for the aerobic exercise interventions were performed from 40% VO2peak (Abolahrari-Shirazi et al., 2018), 60% HRmax reserve (Ahmad et al., 2014; Masterson-Creber et al., 2015), increased heart rate up to 20 bpm above resting (Radi et al., 2017) and 15–18 on the Borg scale (Nilsson et al., 2010) to 70% HRmax reserve (Masterson-Creber et al., 2015), 80% VO2peak (Fu et al., 2013; Prescott et al., 2009), 90% of the ventilator threshold level (Conraads et al., 2004; Conraads et al., 2007; Eleuteri et al., 2013; Kobayashi et al., 2003; van Berendoncks et al., 2010) and as well as 90–95% HRmax (Melo et al., 2019; Wisløff et al., 2007), with the most common exercise intensity 60–75% VO2peak (Delagardelle et al., 2008; Fu et al., 2013; Giallauria et al., 2006a,b; Giallauria et al., 2008; Maria-Sarullo et al., 2006; Passino et al., 2006; Sandri et al., 2012) or 60–70% HRmax reserve (Ahmad et al., 2014; Masterson-Creber et al., 2015).

View all citing articles on Scopus

Clinical trial registration: ClinicalTrials.gov no. NCT00047437.

View full text