Parathyroid hormone-PTH1R signaling in cardiovascular disease and homeostasis

Area of Science:

• Endocrinology
• Cardiovascular Medicine
• Geriatrics

Background:

• Primary hyperparathyroidism (pHPT) is prevalent in aging populations, with a higher incidence in females.
• Current surgical management decisions for pHPT primarily focus on bone, kidney, and calcium levels, often overlooking cardiovascular implications.
• Individuals with pHPT face a significantly increased risk of cardiovascular mortality, especially if not meeting criteria for surgical intervention.

Purpose of the Study:

• To highlight the underestimation of cardiovascular disease (CVD) risk in primary hyperparathyroidism (pHPT) management.
• To emphasize the role of the parathyroid hormone (PTH) 1 receptor (PTH1R) in vascular biology and its implications for CVD.
• To advocate for the integration of CVD risk assessment into the clinical management of pHPT.

Main Methods:

• Review of epidemiological data on pHPT incidence and demographics.
• Analysis of the physiological role of PTH1R in cardiovascular systems.
• Examination of existing clinical guidelines for pHPT surgical management.
• Discussion of pharmacokinetic-pharmacodynamic (PK-PD) relationships of PTH1R ligands.

Main Results:

• Adjusted cardiovascular mortality risk is nearly threefold higher in pHPT patients not meeting surgical cure recommendations.
• The parathyroid hormone (PTH) 1 receptor (PTH1R) is biologically active in the vasculature, linking pHPT to cardiovascular risk.
• Current management strategies for pHPT do not systematically incorporate cardiovascular risk assessment.

Conclusions:

• There is a critical need to identify biomarkers for assessing cardiovascular PTH1R signaling.
• Further research into the PK-PD of PTH1R ligands is required for understanding cardiovascular homeostasis.
• Integrating CVD risk assessment into pHPT management is essential for improving patient outcomes and reducing mortality.