Re-thinking the link between exposure to mercury and blood pressure.

Hypertension or high blood pressure (BP) is a prevalent and manageable chronic condition which is a significant contributor to the total global disease burden. Environmental chemicals, including mercury (Hg), may contribute to hypertension onset and development. Hg is a global health concern, listed by the World Health Organization (WHO) as a top ten chemical of public health concern. Most people are exposed to some level of Hg, with vulnerable groups, including Indigenous peoples and small-scale gold miners, at a higher risk for exposure. We published a systematic review and meta-analysis in 2018 showing a dose-response relationship between Hg exposure and hypertension. This critical review summarizes the biological effects of Hg (both organic and inorganic form) on the underlying mechanisms that may facilitate the onset and development of hypertension and related health outcomes and updates the association between Hg exposure (total Hg concentrations in hair) and BP outcomes. We also evaluated the weight of evidence using the Bradford Hill criteria. There is a strong dose-response relationship between Hg (both organic and inorganic) exposure and BP in animal studies and convincing evidence that Hg contributes to hypertension by causing structural and functional changes, vascular reactivity, vasoconstriction, atherosclerosis, dyslipidemia, and thrombosis. The underlying mechanisms are vast and include impairments in antioxidant defense mechanisms, increased ROS production, endothelial dysfunction, and alteration of the renin-angiotensin system. We found additional 16 recent epidemiological studies that have reported the relationship between Hg exposure and hypertension in the last 5 years. Strong evidence from epidemiological studies shows a positive association between Hg exposure and the risk of hypertension and elevated BP. The association is mixed at lower exposure levels but suggests that Hg can affect BP even at low doses when co-exposed with other metals. Further research is needed to develop robust conversion factors among different biomarkers and standardized measures of Hg exposure. Regulatory agencies should consider adopting a 2 µg/g hair Hg level as a cut-off for public health regulation, especially for adults older than child-bearing age.