In patients with primary hyperparathyroidism (PHPT), parathyroidectomy significantly reduces the risk of major adverse cardiovascular events (MACE), a population-wide target trial emulation (TTE) study in Hong Kong has shown.
“To the best of our knowledge, this is the first TTE study comparing the risk of MACE in patients with PHPT managed with vs without surgery,” researchers from the University of Hong Kong wrote. [Ann Surg 2026;284:928-934]
“Previous studies on the effect of parathyroidectomy in MACE among PHPT patients showed conflicting results,” they noted. “To date, there have been no randomized controlled trials on the impact of parathyroidectomy for PHPT on MACE risk. In addition, Asian data on the topic is nonexistent.” [Brit Med J 2003;327:530-534; Ann Surg 2023;278:e302-e308; JAMA Netw Open 2022;5:e2215396; Bone 2024;185:117130]
In the current TTE study, 6,898 adults with classic PHPT (concomitantly elevated serum calcium [>2.60 mmol/L] and parathyroid hormone [PTH; >6.8 pmol/L] measured on the same day) diagnosed between January 2006 and December 2023 were identified from Hong Kong’s population-wide electronic health record database. The patients (mean age, 65.06 years; female, 71.33 percent) were followed for a median of 4.6 years for the primary composite outcome of MACE (MI, heart failure [HF], stroke, and cardiovascular [CV] mortality).
28 percent lower MACE risk
Among 1,959 patients who underwent parathyroidectomy, 168 experienced MACE. The incidence rate (IR) of MACE was 9.83 per 1,000 person-years (PY) over a median follow-up of 8.27 years.
In the 4,939 patients who received nonsurgical management, 597 experienced MACE. The IR of MACE was 26.87 per 1,000 PY over a median follow-up of 3.22 years.
“Parathyroidectomy led to a 28 percent reduction in risk of MACE in PHPT patients [hazard ratio (HR), 0.72; 95 percent confidence interval (CI), 0.57–0.90; p=0.005],” the researchers reported. “The 10-year cumulative incidence of MACE was lower in the surgery vs nonsurgery group [p<0.001].”
Sensitivity analyses showed consistent reductions in MACE risk with parathyroidectomy.
Significant reductions in risk of MI (HR, 0.58; 95 percent CI, 0.34–0.99; p=0.047), stroke (HR, 0.73; 95 percent CI, 0.55–0.97; p=0.032), and CV mortality (HR, 0.51; 95 percent CI, 0.30–0.88; p=0.016) were also observed in patients treated with parathyroidectomy. However, the association between parathyroidectomy and HF did not reach statistical significance.
Greater benefit in more severe hypercalcaemia
Subgroup analysis showed a more profound reduction in MACE risk among parathyroidectomy-treated patients with higher baseline calcium levels. Risk reduction was 36 percent (HR, 0.64; 95 percent CI, 0.44–0.93) in patients with baseline calcium levels >2.8 mmol/L, and 28 percent (HR, 0.72; 95 percent CI, 0.53–0.98) in those with baseline calcium levels ≤2.8 mmol/L (pinteraction=0.047).
“Therefore, patients with more severe hypercalcaemia should be prioritized for early assessment and definitive surgery,” the researchers suggested.
Practice implications
“Reduction of MACE risk could represent a novel indication for surgery in PHPT, and may inform future practice guidelines,” the researchers noted.
“Worldwide adoption of electronic healthcare systems represents an opportunity, where the same validated algorithm from the current study may be applied to identify potential or untreated PHPT efficiently in massive populations,” they continued. “In cases of incidental hypercalcaemia, prioritized PTH testing and surgical referral, especially for patients with more severe hypercalcaemia [eg, >2.8 mmol/L], may identify and treat a hidden PHPT population that could benefit the most from early surgery.”