Environment-wide association study of cardiovascular and all-cause mortality: analysis of the National Health and Nutrition Examination Survey, 1999-2018.

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Environmental toxicants are increasingly suspected to influence cardiovascular (CV) and all-cause mortality, but previous studies mostly focused on one or a few chemicals. We examined the associations of a wide array of environmental chemicals with CV and all-cause mortality using an exposome-wide approach and the potential mediating role of inflammation in these associations. Data from the National Health and Nutrition Examination Survey (1999-2018) were randomly 60:40 split into a training set and a test set. The mortality rates were determined by the National Center for Health Statistics through a process of correlation with the National Death Index records. Based on the 10th revision of (ICD-10) codes, deaths due to heart disease (ICD 100-I09, I11, I13, and I20-I51) or cerebrovascular disease (I60-I69) were defined as CV mortality. Using the NHANES data, with a median 9.42-year follow-up period, we found that higher concentrations of 2-hydroxynaphthalene (2-NAP) (HR: 1.32, 95%CI: 1.06, 1.64, P-value = 0.014) and 2-hydroxyfluorene (2-FLU) (HR: 1.4, 95%CI: 1.14, 1.73, P-value = 0.002) in the urine, heavy metal cadmium (Cd), and cotinine in the blood were associated with increased risks of both CV and all-cause mortality. We further found 16 chemicals, including polycyclic aromatic hydrocarbons (1-hydroxynaphthalene, 2-hydroxynaphthalene, 3-hydroxyfluorene, 2-hydroxyfluorene and 9-hydroxyfluorene), heavy metals in the urine Cd, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), cotinine and hydroxycotinine, heavy metals in the blood including lead and Cd), volatile organic compounds (benzene, ethylbenzene, styrene, toluene and 2,5-Dimethylfuran) were positively associated with all-cause mortality. Furthermore, we found that C-reactive protein levels partially mediate those associations. In summary, exposure to certain environmental chemicals was associated with CV and all-cause mortality, and C-reactive protein plays a mediation role in those associations. Our findings provided more evidence for preventing and controlling important environmental chemicals to improve people's health.