Primary hyperparathyroidism (pHPT) afflicts our aging population with an incidence approaching 50 per 100 000 patient-years at a female:male ratio of ~3:1. Decisions surrounding surgical management are currently driven by age, hypercalcemia severity, presence of osteoporosis, renal insufficiency, or hypercalciuria with or without nephrolithiasis. Cardiovascular (CV) disease (CVD) is not systematically considered. This is notable since the parathyroid hormone (PTH) 1 receptor (PTH1R) is biologically active in the vasculature, and adjusted CV mortality risk is increased almost threefold in individuals with pHPT who do not meet contemporary recommendations for surgical cure. We provide an overview of epidemiology, pharmacology, and physiology that highlights the need to: (i) identify biomarkers that establish a healthy ‘set point’ for CV PTH1R signaling tone; (ii) better understand the pharmacokinetic–pharmacodynamic (PK-PD) relationships of PTH1R ligands in CV homeostasis; and (iii) incorporate CVD risk assessment into the management of hyperparathyroidism.

中文翻译：

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甲状旁腺激素 - PTH1R 信号在心血管疾病和体内平衡中的作用

原发性甲状旁腺功能亢进症 (pHPT) 困扰着我们的老龄化人口，其发病率接近每 10 万患者年 50 例，女性与男性的比例约为 3:1。目前，围绕手术治疗的决策取决于年龄、高钙血症严重程度、骨质疏松症、肾功能不全或高钙尿症（伴或不伴肾结石）。心血管（CV）疾病（CVD）没有得到系统的考虑。这是值得注意的，因为甲状旁腺激素 (PTH) 1 受体 (PTH1R) 在脉管系统中具有生物活性，并且在不符合当代手术治疗建议的 pHPT 患者中，调整后的 CV 死亡风险几乎增加了三倍。我们对流行病学、药理学和生理学进行了概述，强调需要：(i) 识别为 CV PTH1R 信号音建立健康“设定点”的生物标志物；(ii) 更好地了解 PTH1R 配体在 CV 稳态中的药代动力学 - 药效学 (PK-PD) 关系；(iii) 将 CVD 风险评估纳入甲状旁腺功能亢进症的治疗中。