Environment-wide association study to identify factors associated with hematocrit: evidence from the Guangzhou Biobank Cohort Study

Purpose In randomized controlled trials reducing high hematocrit (Hct) in patients with polycythemia vera protects against cardiovascular disease (CVD) events, whereas increasing Hct in anemia patients causes CVD events. Hct is influenced by environmental and lifestyle factors. Given limited knowledge concerning the drivers of Hct, we took an agnostic approach to identify drivers of Hct. Methods We used an environment-wide association study to identify environmental and lifestyle factors associated with Hct in 20443 older Chinese adults (mean age = 62.7 years) from the Guangzhou Biobank Cohort Study. We evaluated the role of 25 nutrients, 40 environmental contaminants, two metals (only available for 10405 participants), and six lifestyle factors in relation to Hct, adjusted for sex, age, recruitment phase, and socioeconomic position. Results In a mutually adjusted model vitamin A, serum calcium, serum magnesium, and alcohol use were associated with higher Hct, whereas physical activity was associated with lower Hct. Conclusions Despite the difficulty of ascertaining causality, finding both expected (vitamin A and physical inactivity) and novel factors (serum calcium, serum magnesium and alcohol use) strongly associated with Hct illustrates the utility of environment-wide association study to generate hypotheses regarding the potential contribution of modifiable exposures to CVD.