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Endothelin-1 Predicts Hemodynamically Assessed Pulmonary Arterial Hypertension in HIV Infection

BACKGROUND: HIV infection is an independent risk factor for PAH, but the underlying pathogenesis remains unclear. ET-1 is a robust vasoconstrictor and key mediator of pulmonary vascular homeostasis. Higher levels of ET-1 predict disease severity and mortality in other forms of PAH, and endothelin re...

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Autores principales: Parikh, Rushi V., Ma, Yifei, Scherzer, Rebecca, Heringer, Amanda S., Macgregor, John S., Martin, Jeffrey N., Deeks, Steven G., Ganz, Peter, Hsue, Priscilla Y.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4709102/
https://www.ncbi.nlm.nih.gov/pubmed/26752193
http://dx.doi.org/10.1371/journal.pone.0146355
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author Parikh, Rushi V.
Ma, Yifei
Scherzer, Rebecca
Heringer, Amanda S.
Macgregor, John S.
Martin, Jeffrey N.
Deeks, Steven G.
Ganz, Peter
Hsue, Priscilla Y.
author_facet Parikh, Rushi V.
Ma, Yifei
Scherzer, Rebecca
Heringer, Amanda S.
Macgregor, John S.
Martin, Jeffrey N.
Deeks, Steven G.
Ganz, Peter
Hsue, Priscilla Y.
author_sort Parikh, Rushi V.
collection PubMed
description BACKGROUND: HIV infection is an independent risk factor for PAH, but the underlying pathogenesis remains unclear. ET-1 is a robust vasoconstrictor and key mediator of pulmonary vascular homeostasis. Higher levels of ET-1 predict disease severity and mortality in other forms of PAH, and endothelin receptor antagonists are central to treatment, including in HIV-associated PAH. The direct relationship between ET-1 and PAH in HIV-infected individuals is not well described. METHODS: We measured ET-1 and estimated pulmonary artery systolic pressure (PASP) with transthoracic echocardiography (TTE) in 106 HIV-infected individuals. Participants with a PASP ≥ 30 mmHg (n = 65) underwent right heart catheterization (RHC) to definitively diagnose PAH. We conducted multivariable analysis to identify factors associated with PAH. RESULTS: Among 106 HIV-infected participants, 80% were male, the median age was 52 years and 77% were on antiretroviral therapy. ET-1 was significantly associated with higher values of PASP [14% per 0.1 pg/mL increase in ET-1, p = 0.05] and PASP ≥ 30 mmHg [PR (prevalence ratio) = 1.24, p = 0.012] on TTE after multivariable adjustment for PAH risk factors. Similarly, among the 65 individuals who underwent RHC, ET-1 was significantly associated with higher values of mean pulmonary artery pressure and PAH (34%, p = 0.003 and PR = 2.43, p = 0.032, respectively) in the multivariable analyses. CONCLUSIONS: Higher levels of ET-1 are independently associated with HIV-associated PAH as hemodynamically assessed by RHC. Our findings suggest that excessive ET-1 production in the setting of HIV infection impairs pulmonary endothelial function and contributes to the development of PAH.
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spelling pubmed-47091022016-01-15 Endothelin-1 Predicts Hemodynamically Assessed Pulmonary Arterial Hypertension in HIV Infection Parikh, Rushi V. Ma, Yifei Scherzer, Rebecca Heringer, Amanda S. Macgregor, John S. Martin, Jeffrey N. Deeks, Steven G. Ganz, Peter Hsue, Priscilla Y. PLoS One Research Article BACKGROUND: HIV infection is an independent risk factor for PAH, but the underlying pathogenesis remains unclear. ET-1 is a robust vasoconstrictor and key mediator of pulmonary vascular homeostasis. Higher levels of ET-1 predict disease severity and mortality in other forms of PAH, and endothelin receptor antagonists are central to treatment, including in HIV-associated PAH. The direct relationship between ET-1 and PAH in HIV-infected individuals is not well described. METHODS: We measured ET-1 and estimated pulmonary artery systolic pressure (PASP) with transthoracic echocardiography (TTE) in 106 HIV-infected individuals. Participants with a PASP ≥ 30 mmHg (n = 65) underwent right heart catheterization (RHC) to definitively diagnose PAH. We conducted multivariable analysis to identify factors associated with PAH. RESULTS: Among 106 HIV-infected participants, 80% were male, the median age was 52 years and 77% were on antiretroviral therapy. ET-1 was significantly associated with higher values of PASP [14% per 0.1 pg/mL increase in ET-1, p = 0.05] and PASP ≥ 30 mmHg [PR (prevalence ratio) = 1.24, p = 0.012] on TTE after multivariable adjustment for PAH risk factors. Similarly, among the 65 individuals who underwent RHC, ET-1 was significantly associated with higher values of mean pulmonary artery pressure and PAH (34%, p = 0.003 and PR = 2.43, p = 0.032, respectively) in the multivariable analyses. CONCLUSIONS: Higher levels of ET-1 are independently associated with HIV-associated PAH as hemodynamically assessed by RHC. Our findings suggest that excessive ET-1 production in the setting of HIV infection impairs pulmonary endothelial function and contributes to the development of PAH. Public Library of Science 2016-01-11 /pmc/articles/PMC4709102/ /pubmed/26752193 http://dx.doi.org/10.1371/journal.pone.0146355 Text en © 2016 Parikh et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Parikh, Rushi V.
Ma, Yifei
Scherzer, Rebecca
Heringer, Amanda S.
Macgregor, John S.
Martin, Jeffrey N.
Deeks, Steven G.
Ganz, Peter
Hsue, Priscilla Y.
Endothelin-1 Predicts Hemodynamically Assessed Pulmonary Arterial Hypertension in HIV Infection
title Endothelin-1 Predicts Hemodynamically Assessed Pulmonary Arterial Hypertension in HIV Infection
title_full Endothelin-1 Predicts Hemodynamically Assessed Pulmonary Arterial Hypertension in HIV Infection
title_fullStr Endothelin-1 Predicts Hemodynamically Assessed Pulmonary Arterial Hypertension in HIV Infection
title_full_unstemmed Endothelin-1 Predicts Hemodynamically Assessed Pulmonary Arterial Hypertension in HIV Infection
title_short Endothelin-1 Predicts Hemodynamically Assessed Pulmonary Arterial Hypertension in HIV Infection
title_sort endothelin-1 predicts hemodynamically assessed pulmonary arterial hypertension in hiv infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4709102/
https://www.ncbi.nlm.nih.gov/pubmed/26752193
http://dx.doi.org/10.1371/journal.pone.0146355
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