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

Low-grade inflammation and tryptophan-kynurenine pathway activation are associated with adverse cardiac remodeling in primary hyperparathyroidism: the EPATH trial.
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Verheyen N, Meinitzer A, Grübler MR, Ablasser K, Kolesnik E, Fahrleitner-Pammer A, Belyavskiy E, Trummer C, Schwetz V, Pieske-Kraigher E, Voelkl J, Alesutan I, Catena C, Sechi LA, Brussee H, Lewinski DV, März W, Pieske B, Pilz S, Tomaschitz A,


Verheyen N, Meinitzer A, Grübler MR, Ablasser K, Kolesnik E, Fahrleitner-Pammer A, Belyavskiy E, Trummer C, Schwetz V, Pieske-Kraigher E, Voelkl J, Alesutan I, Catena C, Sechi LA, Brussee H, Lewinski DV, März W, Pieske B, Pilz S, Tomaschitz A, (click to view)

Verheyen N, Meinitzer A, Grübler MR, Ablasser K, Kolesnik E, Fahrleitner-Pammer A, Belyavskiy E, Trummer C, Schwetz V, Pieske-Kraigher E, Voelkl J, Alesutan I, Catena C, Sechi LA, Brussee H, Lewinski DV, März W, Pieske B, Pilz S, Tomaschitz A,

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Clinical chemistry and laboratory medicine 2017 04 22() doi 10.1515/cclm-2016-1159
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 left ventricular hypertrophy. 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. 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.

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