Verheyen Nicolas, Fahrleitner-Pammer Astrid, Belyavskiy Evgeny, Gruebler Martin R, Dimai Hans Peter, Amrein Karin, Ablasser Klemens, Martensen Johann, Catena Cristiana, Pieske-Kraigher Elisabeth, Colantonio Caterina, Voelkl Jakob, Lang Florian, Alesutan Ioana, Meinitzer Andreas, März Winfried, Brussee Helmut, Pieske Burkert, Pilz Stefan, Tomaschitz Andreas
Department of Cardiology, Medical University of Graz, Graz, Austria.
Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Graz, Austria.
PLoS One. 2017 Apr 13;12(4):e0173799. doi: 10.1371/journal.pone.0173799. eCollection 2017.
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.
观察性研究表明,骨病与左心室(LV)功能障碍之间存在联系,这种联系在甲状旁腺功能亢进的情况下可能更为明显。因此,我们旨在验证这一假设:在原发性甲状旁腺功能亢进(pHPT)患者队列中,骨转换的循环标志物与左心室功能相关。分析了参与“依普利酮治疗原发性甲状旁腺功能亢进”(EPATH)试验的155例pHPT患者的横断面数据。以左心室射血分数(LVEF, 收缩功能)或二尖瓣早期充盈峰值速度(e',舒张功能)为因变量,并分别以1型前胶原N端前肽(P1NP)、骨钙素(OC)、骨特异性碱性磷酸酶(BALP)或β-交联C末端肽(CTX)为各自的自变量进行多变量线性回归分析。分析还针对血浆甲状旁腺激素、血钙、年龄、性别、糖化血红蛋白、体重指数、24小时平均收缩压、吸烟状况、估算肾小球滤过率、抗高血压治疗、骨质疏松治疗、25-羟基维生素D和N端脑钠肽前体进行了校正。分别观察到P1NP与LVEF(校正β系数 = 0.201,P = 0.035)和e'(β = 0.188,P = 0.042)之间存在独立关系。OC(β = 0.192,P = 0.039)和BALP(β = 0.198,P = 0.030)均与e'独立相关。CTX与LVEF或e'均无相关性。总之,在pHPT情况下,高骨形成标志物与更好的左心室舒张功能以及部分更好的收缩功能独立且反常地相关。未来研究应探索甲状旁腺功能亢进背景下受刺激的骨形成的潜在心脏保护特性。