Association of mercury exposure with blood pressure among adults near artisanal and small scale gold mining in Madre de Dios, Peru.
There have been few studies investigating the association between mercury exposure and blood pressure, with inconsistent results. In this study, the association between hair mercury concentration with mean arterial pressure (MAP) and hypertension were evaluated using data collected in a 2015 cohort study, which sampled 23 communities in Madre de Dios, Peru. This area has recently experienced a rapid increase in artisanal and small scale mining, which is the main anthropogenic source of mercury emissions. Generalized estimating equations were used to account for correlation within communities. Analyses for MAP and hypertension were performed using linear and logistic models, respectively, and confounding variables were included in both models. Due to the significant (p value 0.05) interaction between sex and mercury in both models, the analysis was stratified by sex. In women, there was an inverse association between hair mercury concentration with hypertension (OR: 0.84; 95% CI: 0.50 1.41) and MAP (gMR: 0.99; 95% CI: 0.98 1.008) but these associations were not significant at a 5% significance level. In men, the associations between hair mercury concentration with hypertension (OR: 3.07; 95% CI: 1.36 6.92) and MAP (gMR: 1.024; 95% CI: 1.01 1.04) were positive and significant at a 5% significance level. Differences observed between sex could be attributable to differences in exposure, men eating greater amounts of mercury contaminated fish, or sex hormones, which regulate the distribution and excretion of mercury in the body. Executive Summary Background Few studies have investigated the association between mercury exposure and blood pressure, and even then, results are inconsistent. We evaluated the association of hair mercury concentration with mean arterial pressure (MAP) and hypertension using data from the Amarakaeri Reserve Cohort Study conducted in 2015 among residents of 23 communities in Madre de Dios, Peru. This area has recently experienced a rapid increase in artisanal and small scale mining (ASGM) ASGM is the number one source of anthropogenic mercury emissions globally, releasing toxic mercury into soil and waterways during gold extraction or emitting mercury into the air when the gold amalgam is burned. In aquatic environments, mercury undergoes methylation and biomagnifies up the food chain as methylmercury (MeHg) accumulating in predatory fish in concentrations up to 100 million times greater than that of the water (Chen et al. 2012) Methods The greatest source of human mercury exposure in our study area is the consumption of mercury contaminated fish and wildlife. The majority (80% of mercury in hair is MeHg which is stable over time, making hair the best long term measure of mercury exposure (Berglund et al. 2005) Three tufts of hair ~0.5 cm in diameter) were cut from the root, stored at ambient conditions, and analyzed using a Milestone DMA 80 in Dr. Helen Hsu Kim's laboratory at Duke University (Durham, NC) Blood pressure was measured using an Omron blood pressure monitor (10 Series, BP785) Body mass index (BMI) was calculated using height and weight measurements. Height and weight were measured using a portable height measuring device and Omron HBF 514 scale, respectively. Smoking status and physical activity were self reported on the distributed survey. Serum was collected and analyzed for fatty acids, cholesterol and triglycerides at MedLab Peru, a laboratory in Lima, Peru. Dietary covariates assessed in our analysis, such as extent of western diet and dietary energy and nutrient intake, were estimated using the food frequency questionnaire distributed to the sample population and the 2018 Norwegian Food Composition Table (NFSA 2018) MAP and hypertension were the outcomes of interest: MAP is a continuous measure calculated using diastolic and systolic blood pressure measurements; Hypertension is a binary outcome defined using the 2017 American Heart Association guidelines (average systolic blood pressure greater than or equal to 130 mmHg and/or diastolic blood pressure 80 mmHg) To account for correlated data within community, generalized estimating equations were used to assess the association between hair mercury concentration and the two blood pressure measures. Analysis of hypertension was performed using logistic regression and expressed as odds ratios (ORs) MAP was natural log transformed and analyzed using linear regression, generating geometric mean ratios (gMRs) All measures of association were accompanied by 95% confidence intervals (CI) and p values and adjusted for sex, age, BMI, and whether or not the community was native. In addition, the MAP model controlled for smoking status, serum dihomo g linolenic acid concentration (mol% and serum triglycerides (mg/dL) The hypertension model, on the other hand, controlled for dietary protein intake and serum stearic acid concentration (mol% All models were examined for collinearity and the interaction between mercury and sex. Results In total, our dataset included complete information for 1,432 participants. The majority of our sample population was female (71% Compared to the most recent census (2017) the distribution across age group in our sample population reflects that of Madre de Dios, with 50% of our sample population being between the ages of 18 and 34, and 41% being between 34 and 50 years old. Average hair mercury concentrations were higher in men (3.0 mg/g) compared to women (2.4 mg/g) The average hair mercury concentration was significantly higher in natives versus non natives (4.56 mg/g versus 1.98 mg/g, respectively, p value<0.0001) The average hair mercury concentration increased with age, peaking in native women aged 65 and up (7.7 mg/g) According to our analysis, 14% of our sample population is hypertensive. Of the hypertensive participants 53% were female and 47% were male. There were 337 (24% natives in our sample population and 22% of them were hypertensive, which was double the prevalence of hypertension among non natives (11% The average MAP for the entire sample population was within normal range (84 10 mmHg) When stratified by both sex and native status, the average MAP was still within normal range. MAP was lower among females (82 9 mmHg) compared to males (89 10 mmHg) with the highest MAP occurring among the native male population (91 11 mmHg) In both models, there was a significant interaction between mercury levels and sex. After stratifying by sex, no variables were associated with hypertension at a 5% significance level among women. The association between mercury levels and hypertension in women, although non significant, was inverse (OR: 0.84; 95% CI: 0.50 1.41; p value=0.512) Among men, the association was positive with the odds of hypertension increasing 3 fold (OR: 3.07; 95% CI: 1.36 6.92; p value=0.007) with each 2.7 fold increase in hair mercury concentration. No other variables were significant at a 5% significance level. In the MAP model, mercury levels were also inversely associated with MAP in women (gMR: 0.99; 95% CI: 0.98 1.008; pvalue=0.311) but positively associated in men (gMR: 1.024; 95% CI: 1.01 1.04; pvalue=0.012) The only other variable that was significant at a 5% significance level in men was BMI. With a BMI 30 kg/m, MAP is expected to increase 8.9% (gMR: 1.089; 95% CI: 1.02 1.16; p value=0.010) Among women, age (gMR:1.002; 95% CI:1.00 1.003; p value=0.045) and being a resident of a native community (gMR: 1.04; 95% CI: 1.00 1.089; p value=0.050) were significantly associated with MAP. Conclusion In this study, the association between hair mercury concentration with hypertension and MAP differed by sex, being positive in men and inverse in women. The associations between hair mercury concentration with hypertension and MAP were significant at a 5% significance level among men, but not women. If confirmed, these findings may be attributable to differences in diet, men eating more mercury contaminated fish and wildlife, as well as, the effect of sex hormones, which regulate distribution and excretion of mercury in humans. Hypertension prevalence as well as mercury and MAP levels were higher in native communities compared to non native communities, which may also be attributable to increased consumption of mercurycontaminated fish and wild life. Average mercury and MAP levels were highest among native women aged 65 and up. Further investigation of the differences between native and non native communities, including diet and specifically fish consumption, is warranted. Differences in mercury level between the age groups in these communities should also be further investigated. Additionally, the only interaction evaluated in this analysis was between mercury and sex. The study of other effect modifications with mercury is warranted, including age, serum stearic acid, and dietary protein intake. Introduction In 2010, 1.39 billion (31.1% adults worldwide aged 20 and up were estimated to have hypertension, which was a 5.2% increase in global prevalence from 2000 (Mills et al. 2016) The cut points for hypertension have changed over the years. Most recently, the American Heart Association (AHA) and collaborators published guidelines in 2017 distinguishing hypertension as systolic blood pressure (SBP) greater than or equal to 130 millimeter of mercury (mmHg) and/or diastolic blood pressure (DBP) 80 mmHg (Whelton et al. 2017) Before these guidelines, the cut points for hypertension were 140 and 90 mmHg for SBP and DBP, respectively (Whelton et al. 2017) SBP is the pressure in your blood vessels when your heart beats, and DBP is the pressure in your blood vessels when your heart rests between beats (CDC 2017a) Hypertension is described as the "strongest or one of the strongest risk factors for almost all different cardiovascular diseases" as well as for premature cardiovascular disease (Kjeldsen 2018) Lim et al. (2012) assessed 43 r