The association of arsenic metabolism and blood pressure: a cross-sectional analysis in the MesoAmerican Nephropathy Occupational Study (MANOS)

Growing evidence indicates that arsenic exposure is associated with cardiometabolic outcomes but few studies have investigated the association between arsenic metabolism and blood pressure. We evaluated cross-sectional associations between urinary arsenic metabolites and blood pressure outcomes—systolic and diastolic blood pressure, pulse pressure, and mean arterial pressure—among 393 male participants in the MesoAmerican Nephropathy Occupational Study (MANOS) in El Salvador and Nicaragua. We applied three modeling approaches: (1) conventional models assessing each urinary arsenic species [inorganic arsenic (InAs), monomethylated arsenic (MMA), and dimethylated arsenic (DMA)] individually as a percentage of the sum of inorganic and methylated arsenic; (2) leave-one-out models evaluating the relative effects of two species while holding the third constant; and (3) principal components analysis (PCA) representing methylation steps of arsenic metabolism. In conventional models adjusted for age, body mass index, worksite, pesticide use, smoking status, and water consumption, participants with higher DMA% showed increased systolic blood pressure (β = 0.17 mmHg per percentage point increase in DMA%; 95% CI: 0.019, 0.33) and pulse pressure (β = 0.14 mmHg per percentage point increase in DMA%; 95% CI: 0.01, 0.26), while participants with higher MMA% showed decreased systolic blood pressure (β = -0.37 mmHg per percentage point increase in MMA%; 95% CI: -0.67, -0.07) and pulse pressure (β = -0.31 mmHg per percentage point increase in MMA%; 95% CI: -0.55, -0.06). In leave-one-out models, higher DMA%, as a result of lower MMA%, was associated with increased systolic blood pressure (β = 0.33 mmHg per percentage point increase in DMA%; 95% CI: -0.007, 0.67) and pulse pressure (β = 0.29 mmHg per percentage point increase in DMA%; 95% CI: 0.01, 0.56). PCA results supported these findings. The second methylation step from MMA to DMA was associated with higher systolic blood pressure (β = 0.93 mmHg; 95% CI: 0.11, 1.75) and pulse pressure (β = 0.74 mmHg; 95% CI: 0.07, 1.40). Our findings suggest that biomarkers of efficient methylation of InAs to DMA are associated with higher blood pressure compared to partial methylation to MMA, highlighting the importance of arsenic metabolism profiles in cardiovascular risk assessment.