title: Biomarkers in Trypanosoma cruzi-infected and uninfected individuals with varying severity of cardiomyopathy in Santa Cruz, Bolivia.
abstract: BACKGROUND
  Twenty to thirty percent of persons with Trypanosoma cruzi infection eventually develop cardiomyopathy. If an early indicator were to be identified and validated in longitudinal studies, this could enable treatment to be prioritized for those at highest risk. We evaluated cardiac and extracellular matrix remodeling markers across cardiac stages in T. cruzi infected (Tc+) and uninfected (Tc-) individuals.
  
  
  METHODS
  Participants were recruited in a public hospital in Santa Cruz, Bolivia and assigned cardiac severity stages by electrocardiogram and echocardiogram. BNP, NTproBNP, CKMB, troponin I, MMP-2, MMP-9, TIMP-1, TIMP-2, TGFb1, and TGFb2 were measured in specimens from 265 individuals using multiplex bead systems. Biomarker levels were compared between Tc+ and Tc- groups, and across cardiac stages. Receivers operating characteristic (ROC) curves were created; for markers with area under curve>0.60, logistic regression was performed.
  
  
  RESULTS
  Analyses stratified by cardiac stage showed no significant differences in biomarker levels by Tc infection status. Among Tc+ individuals, those with cardiac insufficiency had higher levels of BNP, NTproBNP, troponin I, MMP-2, TIMP-1, and TIMP-2 than those with normal ejection fraction and left ventricular diameter. No individual marker distinguished between the two earliest Tc+ stages, but in ROC-based analyses, MMP-2/MMP-9 ratio was significantly higher in those with than those without ECG abnormalities.
  
  
  CONCLUSIONS
  BNP, NTproBNP, troponin I, MMP-2, TIMP-1, and TIMP-2 levels rose with increasing severity stage but did not distinguish between Chagas cardiomyopathy and other cardiomyopathies. Among Tc+ individuals without cardiac insufficiency, only the MMP-2/MMP-9 ratio differed between those with and without ECG changes.
authors.affiliation: New York University School of Medicine, New York, New York, United States of America.
authors.forename: Emi E
authors.initials: EE
authors.lastname: Okamoto
authors.affiliation: New York University School of Medicine, New York, New York, United States of America.
authors.forename: Jacqueline E
authors.initials: JE
authors.lastname: Sherbuk
authors.affiliation: Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Eva H
authors.initials: EH
authors.lastname: Clark
authors.affiliation: Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
authors.forename: Morgan A
authors.initials: MA
authors.lastname: Marks
authors.affiliation: Beth Israel Deaconess, Boston, Massachusetts, United States of America.
authors.forename: Omar
authors.initials: O
authors.lastname: Gandarilla
authors.affiliation: Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
authors.forename: Gerson
authors.initials: G
authors.lastname: Galdos-Cardenas
authors.affiliation: Hospital Nacional Guillermo Almenara Ingoyen, EsSalud, Lima, Peru.
authors.forename: Angel
authors.initials: A
authors.lastname: Vasquez-Villar
authors.affiliation: Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
authors.forename: Jeong
authors.initials: J
authors.lastname: Choi
authors.affiliation: University of Michigan School of Medicine, Ann Arbor, Michigan, United States of America.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Crawford
authors.forename: Rose Q
authors.initials: RQ
authors.lastname: Do
authors.affiliation: VA Medical Center and University of Colorado School of Medicine, Denver, Colorado, United States of America.
authors.forename: Rose
authors.initials: R
authors.lastname: Q
authors.affiliation: Hartford Hospital, Hartford, Connecticut, United States of America.
authors.forename: Antonio B
authors.initials: AB
authors.lastname: Fernandez
authors.affiliation: Universidad Catolica Boliviana, Santa Cruz, Plurinational State of Bolivia.
authors.forename: Rony
authors.initials: R
authors.lastname: Colanzi
authors.affiliation: Universidad Catolica Boliviana, Santa Cruz, Plurinational State of Bolivia.
authors.forename: Jorge Luis
authors.initials: JL
authors.lastname: Flores-Franco
authors.affiliation: Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Gilman
authors.affiliation: University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Caryn
authors.initials: C
authors.lastname: Bern
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001838:Bolivia; D009202:Cardiomyopathies / Q000097:blood / Q000175:diagnosis*; D002598:Chagas Cardiomyopathy / Q000097:blood / Q000175:diagnosis*; D004562:Electrocardiography; D005260:Female; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D012372:ROC Curve; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D019716:Tissue Inhibitor of Metalloproteinase-2; D020780:Matrix Metalloproteinase 9