Cardiovascular Health in Patients With Primary Hyperparathyroidism: Effect of Parathyroidectomy on Cardiovascular Health: A Randomized Controlled Trial

Background:

The cardiovascular manifestation of primary hyperparathyroidism (PHPT) has been debated in many years. PHPT was once a highly symptomatic disease with severe symptoms. Today, the clinical presentation of the disease is often asymptomatic or with few symptoms at diagnose. This may be the reason why the literature regarding this area is conflicting. Studies have observed an increased mortality cause by cardiovascular diseases (CVD) in moderate to severe disease, whereas other studies with focus on mild disease observed no increased risk of mortality. A shift in the clinical presentation of the disorder to a more asymptomatic appearance makes it pivotal to investigate CVD risk in patients with PHPT before and after surgery. Large-arterial stiffness is known to be a predictor of cardiovascular events and all-cause mortality. Measurement of carotid-femoral pulse wave velocity (PWV) is considered as the gold standard for non-invasive measurement of arterial stiffness. To date, only few studies have investigated the relationship between PWV and PHPT. In three prospective studies the authors reported a significant increase in PWV preoperative in PHPT patients compared to controls. 6-month after parathyroidectomy two of the studies observed a significant decrease in PWV, where one study observed a non-significant decrease. Another study by Ring et al observed only a slightly, but significant increased PWV in PHPT patients compared to controls and no changes after surgery at 1-year follow-up. However, a study by Tordjman et al observed no differences in PWV among PHPT patients compared to controls. In addition, other studies have explored the relationships between arterial stiffness and PHPT using either augmentation index (AIx) or carotid intima-media thickness (IMT) as predictors for arterial stiffness. Three studies with focus on AIx reported an increased AIx in PHPT patients, whereas two other studies observed no increased AIx in PHPT patients compared to controls. Using the IMT methods, two studies reported a significant increased IMT in PHPT patient preoperative compared to controls and a significant decrease after parathyroidectomy. Furthermore, a study by Walker et al observed an increased IMT in PHPT patients compared to controls but in a subsequent follow-up study there was no changes in IMT after surgery. In contrast, one study reported no differences in IMT in PTHP patients before and after surgery. Most research so far has focussed on different methods for measurements of arterial stiffness which makes a comparison among studies difficult. More research with focus on one of the methods is necessary.

Another clinical aspect of PHPT is the increased prevalence of hypertension compared to the general population. Previous research findings into parathyroidectomy's effect on hypertension have been inconsistent and contradictory. Four studies reported no effect of parathyroidectomy on preoperative hypertensive patients and in two studies they observed an increased incidence in hypertension after surgery. However, in four other studies they observed a significant postoperative reduction in systolic and diastolic BP among known hypertensive patients at follow-up.

Nevertheless, much uncertainty still exists and more research investigating the relationship between BP and arterial stiffness pre- and postoperative is required. PWV is considered the gold standard for non-invasive measurements of arterial stiffness and a predictor for cardiovascular events and all-cause mortality. It is therefore the best approach to assess the association of PHPT and cardiovascular risk in combination with BP. In addition, until now study design has been prospective with small population sizes. Therefore, we need to perform a randomized controlled trial (RCT) comparing arterial stiffness and blood pressure (BP) in patients with mild PHPT pre- and post-operative. This study will be the first performed randomized controlled trial (RCT) investigating arterial stiffness and BP in patients with PHPT. Hopefully, this study will be able to establish the cardiovascular risk in patients with mild PHPT and have an influence on future international guidelines for management of PHPT.

Aim: