High normal parathyroid hormone and cardiovascular and total mortality: sex and age disparities in the ELSA-Brasil study

BACKGROUND: Elevated parathyroid hormone (PTH) levels have been linked to higher cardiovascular (CV) and all-cause mortality in individuals with hyperparathyroidism or high-risk conditions. However, it remains uncertain whether sex- and age-related differences influence these associations among normocalcemic and middle-aged adults from the general population. METHODS: We analyzed 4,736 participants from the ELSA-Brasil study (mean age, 51.7 years; 55% females), followed for a median of 11.2 years. Baseline serum PTH was measured by electrochemiluminescence immunoassay. Associations of PTH with outcomes were assessed using Cox regression for all-cause mortality, reporting hazard ratios (HRs), and Fine-Gray models for CV mortality, accounting for competing risks and reporting subdistribution hazard ratios (sHRs), adjusted for total calcium and other relevant covariates. RESULTS: A baseline PTH concentration >56 pg/mL was independently associated with higher CV mortality (sHR 1.92; 95% CI 1.22-3.01) and all-cause mortality (HR 1.61; 95% CI 1.25-2.07). Sex- and age-stratified analyses showed that females with elevated PTH had a 179% increased CV mortality risk (sHR 2.79; 95% CI 1.37-5.70), whereas no significant association was seen in males. Elevated PTH was also associated with increased CV mortality in adults ≤64 years (sHR 1.80; 95% CI 1.05-3.09), but not in older individuals. For all-cause mortality, PTH >56 pg/mL conferred higher risk in both females (HR 1.75; 95% CI 1.15-2.66) and males (HR 1.59; 95% CI 1.16-2.19), with consistent associations across both age groups (≤64 and >64 years). CONCLUSIONS: In this large, community-based cohort, PTH levels at the upper end of the reference range were associated with greater CV and all-cause mortality. The excess CV risk was restricted to females and younger adults, suggesting that PTH may serve as an early, sex-sensitive biomarker of cardiometabolic risk.