Urinary Metal Mixtures and Incident Metabolic Syndrome in Midlife Women: the Study of Women’s Health Across the Nation (SWAN)

Abstract

BACKGROUND AND AIM: Exposure to metals may contribute to the development of metabolic syndrome (MetS); however, evidence from midlife women who are at greater risk of cardiometabolic disease is limited. We prospectively examined the associations of 15 urinary metal concentrations with incident MetS in the Study of Women’s Health Across the Nation Multi-Pollutant Study. METHODS: The sample included 947 White, Black, Chinese and Japanese women from 5 study sites in the United States, aged 45-56 years and free of MetS at baseline (1999-2000), followed through 2017. Urinary concentrations of 15 metals, including arsenic, barium, cadmium, cobalt, cesium, copper, mercury, manganese, molybdenum, nickel, lead, antimony, tin, thallium, and zinc, were quantified at baseline. Incident MetS was identified annually as the presence of at least 3 of the following 5 components: high blood pressure, impaired fasting glucose, abdominal obesity, high triglycerides, and low high-density lipoprotein cholesterol. RESULTS:After adjustment for potential confounders, the hazard ratios (HR) (95% confidence interval (CI)) for MetS associated with each doubling of urinary metal concentration was 1.14 (1.08, 1.23) for arsenic, 1.14 (1.01, 1.29) for cobalt, and 1.20 (1.06, 1.37) for zinc, in Cox proportional hazards models. Positive associations of urinary arsenic with high blood pressure and impaired fasting glucose, positive associations of urinary cobalt with high blood pressure and abdominal obesity, and positive associations of urinary zinc with high blood pressure, impaired fasting glucose, abdominal obesity, and high triglyceride were observed. In the quantile-based g-computation assessing the joint effect of metal mixtures, increasing urinary arsenic, cobalt, and zinc concentrations by one quartile was associated with a higher incidence of MetS (HR=1.73, 95% CI: 1.21, 2.48). CONCLUSIONS:Higher urinary arsenic, cobalt, and zinc concentrations were associated with an elevated incidence of MetS in midlife women. Future studies should confirm these findings and further investigate the underlying mechanisms. KEYWORDS: Metals, mixtures, metabolic syndrome, women, cohort study.