Parathyroidectomy Reduced the Risk of Incident Major Adverse Cardiovascular Events Among Patients With Primary Hyperparathyroidism—Results From a Population-Wide Target Trial Emulation Study

OBJECTIVE: Using target trial emulation to compare the risk of major adverse cardiovascular events (MACE) in patients with primary hyperparathyroidism (PHPT) treated with versus without surgery. BACKGROUND: PHPT was associated with increased cardiovascular morbidity and mortality. However, the impact of parathyroidectomy on cardiovascular outcomes in PHPT remained uncertain. METHODS: The electronic health database encompassing the entire public health system in Hong Kong from 2006 to 2023 was used to emulate a randomized controlled trial. PHPT was defined by concomitantly raised serum calcium and parathyroid hormone. MACE was defined by myocardial infarction, stroke, heart failure, or cardiovascular mortality. Patients with MACE before PHPT diagnosis were excluded. Marginal structural model with inverse probability of treatment weighting, modelling surgery as a time-varying exposure was applied. MACE risk between surgery versus nonsurgery management was compared with the Cox proportional hazards model. Sensitivity analyses censored patients developing MACE <1 year, and excluded patients with follow-up <1 year. RESULTS: Among 6898 PHPT patients identified, 1959 (28.4%) underwent parathyroidectomy. Five hundred ninety-seven MACE occurred in the nonsurgery group (median follow-up 3.22 y, incidence rate: 26.87/1000 person-years), versus 168 in the surgery group (median follow-up 8.27 y, incidence rate: 9.83/1000 person-years). Surgery reduced the risk of MACE significantly (HR: 0.72; 95% CI: 0.57-0.90, P=0.005). Patients with higher calcium levels (>2.8 mmol/L) had more profound MACE risk reduction (HR: 0.64 [95% CI: 0.44-0.93] vs. 0.72 [95% CI: 0.53-0.98]; interaction P=0.047). Sensitivity analyses showed consistent findings. CONCLUSION: Parathyroidectomy reduced the risk of MACE in patients with PHPT.