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

Abstract

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 "Eplerenone in Primary Hyperparathyroidism" (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 pro-brain B-type natriuretic peptide. Independent relationships were observed between P1NP and LVEF (adjusted β-coefficient = 0.201, P = 0.035) and e' (β = 0.188, P = 0.042), respectively. OC (β = 0.192, P = 0.039) and BALP (β = 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.