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Licensed Unlicensed Requires Authentication Published by De Gruyter April 22, 2017

Low-grade inflammation and tryptophan-kynurenine pathway activation are associated with adverse cardiac remodeling in primary hyperparathyroidism: the EPATH trial

  • Nicolas Verheyen EMAIL logo , Andreas Meinitzer , Martin Robert Grübler , Klemens Ablasser , Ewald Kolesnik , Astrid Fahrleitner-Pammer , Evgeny Belyavskiy , Christian Trummer , Verena Schwetz , Elisabeth Pieske-Kraigher , Jakob Voelkl , Ioana Alesutan , Cristiana Catena , Leonardo Alberto Sechi , Helmut Brussee , Dirk von Lewinski , Winfried März , Burkert Pieske , Stefan Pilz and Andreas Tomaschitz

Abstract

Background:

Primary hyperparathyroidism (pHPT) is associated with low-grade inflammation, left ventricular hypertrophy and increased cardiovascular mortality, but the association between inflammatory markers and parameters of adverse cardiac remodeling is unknown. We investigated the relationship between C-reactive protein (CRP), the essential amino acid tryptophan and its pro-inflammatory derivatives kynurenine and quinolinic acid (QUIN) with echocardiographic parameters.

Methods:

Cross-sectional baseline data from the “Eplerenone in Primary Hyperparathyroidism” trial were analyzed. Patients with any acute illness were excluded. We assessed associations between CRP, serum levels of tryptophan, kynurenine and QUIN and left ventricular mass index (LVMI), left atrial volume index (LAVI) and E/e′.

Results:

Among 136 subjects with pHPT (79% females), 100 (73%) had arterial hypertension and the prevalence of left ventricular hypertrophy was 52%. Multivariate linear regression analyses with LVMI, LAVI and E/e′ as respective dependent variables, and C-reactive protein and tryptophan, kynurenine and QUIN as respective independent variables were performed. Analyses were adjusted for age, sex, blood pressure, parathyroid hormone, calcium and other cardiovascular risk factors. LVMI was independently associated with CRP (adjusted β-coefficient=0.193, p=0.030) and QUIN (β=0.270, p=0.007), but not kynurenine. LAVI was related with CRP (β=0.315, p<0.001), kynurenine (β=0.256, p=0.005) and QUIN (β=0.213, p=0.044). E/e′ was related with kynurenine (β=0.221, p=0.022) and QUIN (β=0.292, p=0.006). Tryptophan was not associated with any of the remodeling parameters.

[Correction added after online publication (22 April 2017: The sentence “Among 136 subjects with pHPT (79% females), 100 (73%) had left ventricular hypertrophy.” was corrected to “Among 136 subjects with pHPT (79% females), 100 (73%) had arterial hypertension and the prevalence of left ventricular hypertrophy was 52%.”]

Conclusions:

Cardiac remodeling is common in pHPT and is associated with low-grade inflammation and activation of the tryptophan-kynurenine pathway. The potential role of kynurenine and QUIN as cardiovascular risk factors may be further investigated in future studies.

Acknowledgments

We thank the Laboratory of the Division of Endocrinology and Metabolism for its work and support to the present research. Probes used for the present analyses were partly provided by the Biobank Graz.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: The study was funded by the Austrian National Bank (Jubilaeumsfond: project no. 14621) and by the Austrian Society for Bone and Mineral Research (Felix-Bronner Grant 2014, Project Prize 2014).

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organizations played no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Supplemental Material:

The online version of this article (DOI: https://doi.org/10.1515/cclm-2016-1159) offers supplementary material, available to authorized users.


Received: 2016-12-19
Accepted: 2017-3-24
Published Online: 2017-4-22
Published in Print: 2017-6-27

©2017 Walter de Gruyter GmbH, Berlin/Boston

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