Use of biomarkers of metals to improve prediction performance of cardiovascular disease mortality

Abstract Background Whether including additional environmental risk factors improves cardiovascular disease (CVD) prediction is unclear. We attempted to improve CVD mortality prediction performance beyond traditional CVD risk factors by additionally using metals measured in the urine and blood and with statistical machine learning methods. Methods Our sample included 7,085 U.S. adults aged 40 years or older from the National Health and Nutrition Examination Survey 2003–2004 through 2015–2016, linked with the National Death Index through December 31, 2019. Data were randomly split into a 50/50 training dataset used to construct CVD mortality prediction models (n = 3542) and testing dataset used as validation to assess prediction performance (n = 3543). Relative to the traditional risk factors (age, sex, race/ethnicity, smoking status, systolic blood pressure, total and high-density lipoprotein cholesterol, hypertension, and diabetes), we compared models with an additional 17 blood and urinary metal concentrations. To build the prediction models, we used Cox proportional hazards, elastic-net (ENET) penalized Cox, and random survival forest methods. Results 420 participants died from CVD with 8.8 mean years of follow-up. Blood lead, cadmium, and mercury were associated (p