Relationship between bone turnover and left ventricular function in primary hyperparathyroidism: The EPATH trial

Observational studies suggested a link between bone disease and left ventricular (LV) dysfunction that may be pronounced in hyperparathyroid conditions. We therefore aimed to test the hypothesis that circulating markers of bone turnover correlate with LV function in a cohort of patients with primary hyperparathyroidism (pHPT). Cross-sectional data of 155 subjects with pHPT were analyzed who participated in the \uaaEplerenone in Primary Hyperparathyroidism \uba (EPATH) Trial. Multivariate linear regression analyses with LV ejection fraction (LVEF, systolic function) or peak early transmitral filling velocity (e', diastolic function) as dependent variables and N-terminal propeptide of procollagen type 1 (P1NP), osteocalcin (OC), bone-specific alkaline phosphatase (BALP), or beta-crosslaps (CTX) as the respective independent variable were performed. Analyses were additionally adjusted for plasma parathyroid hormone, plasma calcium, age, sex, HbA1c, body mass index, mean 24-hours systolic blood pressure, smoking status, estimated glomerular filtration rate, antihypertensive treatment, osteoporosis treatment, 25-hydroxy vitamin D and N-terminal probrain B-type natriuretic peptide. Independent relationships were observed between P1NP and LVEF (adjusted \u3b2-coefficient = 0.201, P = 0.035) and e' (\u3b2 = 0.188, P = 0.042), respectively. OC (\u3b2 = 0.192, P = 0.039) and BALP (\u3b2 = 0.198, P = 0.030) were each independently related with e'. CTX showed no correlations with LVEF or e'. In conclusion, high bone formation markers were independently and paradoxically related with better LV diastolic and, partly, better systolic function, in the setting of pHPT. Potentially cardio-protective properties of stimulated bone formation in the context of hyperparathyroidism should be explored in future studies

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 \u201cEplerenone in Primary Hyperparathyroidism\u201d 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\u2032. 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\u2032 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 \u3b2-coefficient = 0.193, p = 0.030) and QUIN (\u3b2 = 0.270, p = 0.007), but not kynure- nine. LAVI was related with CRP (\u3b2 = 0.315, p < 0.001), kynurenine (\u3b2 = 0.256, p = 0.005) and QUIN (\u3b2 = 0.213, p = 0.044). E/e\u2032 was related with kynurenine (\u3b2 = 0.221, p = 0.022) and QUIN (\u3b2 = 0.292, p = 0.006). Tryptophan was not associated with any of the remodeling parameters