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: Emi E Okamoto, Jacqueline E Sherbuk, Eva H Clark, Morgan A Marks, Omar Gandarilla, Gerson Galdos-Cardenas, Angel Vasquez-Villar, Jeong Choi, Thomas C Crawford, Rose Q Do, Rose Q, Antonio B Fernandez, Rony Colanzi, Jorge Luis Flores-Franco, Robert H Gilman, Caryn Bern, Chagas Disease Working Group in Bolivia and Peru
• Journal: PLoS neglected tropical diseases (PLoS Negl Trop Dis) Vol. 8 Issue 10 Pg. e3227 (Oct 2014) ISSN: 1935-2735 [Electronic] United States
• PMID: 25275382 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Peptide Fragments
• TIMP1 protein, human
• TIMP2 protein, human
• Tissue Inhibitor of Metalloproteinase-1
• pro-brain natriuretic peptide (1-76)
• Natriuretic Peptide, Brain
• Tissue Inhibitor of Metalloproteinase-2
• Matrix Metalloproteinase 9

Topics

• Adult
• Aged
• Biomarkers (blood)
• Bolivia
• Cardiomyopathies (blood, diagnosis)
• Chagas Cardiomyopathy (blood, diagnosis)
• Electrocardiography
• Female
• Humans
• Male
• Matrix Metalloproteinase 9 (blood)
• Middle Aged
• Natriuretic Peptide, Brain (blood)
• Peptide Fragments (blood)
• ROC Curve
• Tissue Inhibitor of Metalloproteinase-1 (blood)
• Tissue Inhibitor of Metalloproteinase-2 (blood)