The association of urinary heavy metal exposure with frailty susceptibility and mortality in middle-aged and older adults: a population-based study

Heavy metals’ presence as environmental pollutants has a close link to adverse health effects. Frailty, a clinical syndrome hallmarked by elevated vulnerability to stressors, presents a substantial challenge in healthcare. However, the association between exposure to heavy metals and frailty largely remains unexplored. Utilizing data from the National Health and Nutrition Examination Survey (NHANES) spanning 2003–2018 and correlated with the U.S. National Death Index (NDI) from 2019, we investigated mortality outcomes. Logistic regression, Cox regression, Kaplan-Meier survival curves, weighted quantile-sum (WQS) regression, and Bayesian kernel machine regression (BKMR) were employed to assess the association between heavy metal exposure and frailty incidence and mortality in the frail population. Eight metals were measured in urine using inductively coupled plasma mass spectrometry with values adjusted for urinary creatinine, which was used to reflect heavy metal exposure. The cohort incorporated 5370 female participants aged 45 and above, with 1518 diagnosed with frailty. The findings indicated a substantial correlation between exposure to specific heavy metals, namely tungsten (odds ratio [OR]: 1.94, 95% confidence interval [CI]: 1.31–2.89), cobalt (OR: 1.64, 95% CI: 1.40–1.93), cadmium (OR: 1.93, 95% CI: 1.52–2.43), and uranium (OR: 7.36, 95% CI: 1.53–35.28), and an elevated risk of frailty. WQS and BKMR regression models identified cadmium, cobalt, and tungsten as main contributors to frailty. Cox regression analysis, after adjustment for covariates, suggested that the higher the exposure levels to cadmium and lead, the higher the risk of death in frail patients, with associated hazard ratios (HR) of 95% CI: 1.96 (1.53, 2.52) and 1.30 (1.13, 1.49), respectively. Our study revealed a significant positive correlation between exposure to heavy metal mixtures and frailty onset in middle-aged and older adults, along with increased mortality in frail patients. Cobalt, cadmium, and tungsten emerged as prominent contributors to frailty, with cobalt and cadmium directly impacting the long-term life expectancy of frail patients.