Metal Mixtures Mediate the Socioeconomic Gradient in Blood Pressure: A Four-Way Decomposition in a Prospective Rural Bangladeshi Cohort

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Background: The causal mechanisms by which socioeconomic status (SES) affects blood pressure (BP) in low- and middle-income countries (LMICs) remain poorly understood. We examined the effects of SES on BP, and the extent to which disparities in metal mixture exposures mediate these effects among rural Bangladeshi adults. Methods: This study included 5923 participants from the Bangladesh Vitamin E and Selenium Trial (BEST), a prospective cohort followed for six years with repeated BP assessments at baseline and three biennial follow-ups. Baseline exposures included SES indicators: education and agricultural land ownership (socioeconomic position, SEP), and metal mixtures: blood arsenic, lead, selenium, and urinary arsenic. We applied the parametric and mediational g-formula, along with generalized weighted quantile sum regression, to estimate total, direct, and indirect effects of SES on BP outcomes and conduct causal mediation analysis with four-way decomposition. Results: Higher education increased BP, whereas SEP decreased the elevation of BP. Both higher education and SEP lowered metal exposures. Metal mixtures mediated the effects of SES on BP. For example, higher education increased systolic blood pressure (SBP) by 3.53 mmHg (95% CI: 2.23, 4.82), while the pure natural indirect effect showed a protective pathway of -0.44 mmHg (95% CI: -0.62, -0.27) through reduced metals. For SEP, nearly 42% of its protective effect on SBP was mediated by lower metal exposures. Conclusions: Socioeconomic differentials in BP outcomes in rural Bangladesh are partly explained by inequalities in metal mixture exposures. Reducing metal exposures may mitigate SES-related disparities in BP measures in LMICS.

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