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

Background: Primary hyperparathyroidism (pHPT) is associated with low-grade inflammation, left ventricular hypertrophy and increased cardiovascular mortality, but the association between inflammatory markers and para- meters 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 tryp- tophan, 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 respec- tive dependent variables, and C-reactive protein and tryp- tophan, 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 indepen- dently associated with CRP (adjusted β-coefficient = 0.193, p = 0.030) and QUIN (β = 0.270, p = 0.007), but not kynure- nine. 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.