Identifying biomarker patterns and predictors of inflammation and myocardial stress.
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.


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.
School of Nursing and Department of Biomedical Informatics, Columbia University, New York, New York. Electronic address: rm3284@cumc.columbia.edu.
Ruth M
RM
Masterson Creber
School of Nursing, Oregon Health and Science University, Portland, Oregon.
Christopher S
CS
Lee
School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Kenneth
K
Margulies
School of Nursing, University of Pennsylvania, Philadelphia, Pennsylvania.
Barbara
B
Riegel
D015415:Biomarkers / Q000032:analysis / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis*; D005080:Exercise Test / Q000379:methods; D005081:Exercise Therapy / Q000379:methods*; D005260:Female; D006333:Heart Failure / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011237:Predictive Value of Tests; D011379:Prognosis; D012720:Severity of Illness Index; D016896:Treatment Outcome
D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D002097:C-Reactive Protein
Heart failure; biological markers; exercise therapy; inflammation