Arsenic Exposure and Hypertension: A Systematic Review
Eleven studies, published between 1995 and 2011, were identified (Table 1). All studies meeting the inclusion criteria were cross-sectional and published in English. Combined, the studies covered arsenic exposure and hypertension outcomes for > 20,000 individuals. Eight studies were conducted at moderate to high levels of exposure (average levels in drinking water ≥ 50 μg/L or occupational studies) (Chen CJ et al. 1995; Chen Y 2007; Dastgiri et al. 2010; Guo et al. 2007; Jensen and Hansen 1998; Kwok et al. 2007; Rahman et al. 1999; Yildiz et al. 2008), and three studies were conducted at low levels of exposure (average levels in drinking water < 50 μg/L) (Jones et al. 2011; Wang SL et al. 2007; Zierold et al. 2004). Ten studies were conducted in general populations (two from Taiwan, two from Bangladesh, two from Inner Mongolia, two from the United States, one from Turkey, and one from Iran) (Chen CJ et al. 1995; Chen Y 2007; Dastgiri et al. 2010; Guo et al. 2007; Jones et al. 2011; Kwok et al. 2007; Rahman et al. 1999; Wang SL et al. 2007; Yildiz et al. 2008; Zierold et al. 2004). One study was conducted in an occupational setting in Denmark (Jensen and Hansen 1998). Five studies measured arsenic concentrations in drinking water (Chen CJ et al. 1995; Chen Y 2007; Kwok et al. 2007; Rahman et al. 1999; Zierold et al. 2004), three compared areas of high and low arsenic concentrations in drinking water (Dastgiri et al. 2010; Guo et al. 2007; Yildiz et al. 2008), two studies used biomarkers (hair, Wang SL et al. 2007; urine, Jones et al. 2011), and one study assigned arsenic exposure based on job title (Jensen and Hansen 1998). Eight studies assessed hypertension as the end point of interest (Chen CJ et al. 1995; Chen Y 2007; Guo et al. 2007; Jones et al. 2011; Rahman et al. 1999; Wang SL et al. 2007; Yildiz et al. 2008; Zierold et al. 2004), five studies reported differences in mean SBP (Chen Y et al. 2007; Dastgiri et al. 2010; Jensen and Hansen 1998; Jones et al. 2011; Kwok et al. 2007), and four studies reported differences in mean DBP (Chen Y et al. 2007; Dastgiri et al. 2010; Jones et al. 2011; Kwok et al. 2007).
Five studies measured arsenic in drinking water at the individual level (Chen Y et al. 2007; Jones et al. 2011; Kwok et al. 2007; Wang SL et al. 2007; Yildiz et al. 2008); three of these studies measured individual arsenic exposure based on measured well water concentrations (Chen Y et al. 2007; Kwok et al. 2007; Yildiz et al. 2008), and two studies used a biomarker of exposure (Table 2) (Jones et al. 2011; Wang SL et al. 2007). Five studies defined hypertension based on established cutoffs for SBP and DBP levels measured with a standardized protocol and self-reported physician diagnosis or antihypertensive treatment (Chen CJ et al. 1995; Chen Y 2007; Jones et al. 2011; Rahman et al. 1999; Wang SL et al. 2007). Five of the 11 studies did not adjust for potential confounders (Dastgiri et al. 2010; Guo et al. 2007; Jensen and Hansen 1998; Wang SL et al. 2007; Yildiz et al. 2008). Other studies adjusted at least for age, sex, and BMI.
For the association of hypertension with arsenic exposure, five of the eight studies found a positive association (Chen CJ et al. 1995; Guo et al. 2007; Rahman et al. 1999; Wang SL et al. 2007; Zierold et al. 2004). Among the studies that assessed hypertension at moderate to high levels of exposure, the OR estimates comparing highest with lowest arsenic exposure groups ranged from 0.71 (95% CI: 0.18, 2.63) in a small study in Turkey (Yildiz et al. 2008) to 16.5 (95% CI: 2.8, 668.5) in a study in Inner Mongolia (Figure 2) (Guo et al. 2007). The two studies from Bangladesh provided inconsistent results: an OR of 3.0 (95% CI: 1.5, 5.8) in the study by Rahman et al. (1999) and an OR of 1.02 (95% CI: 0.84, 1.23) in the study by Chen Y et al. (2007). Among the studies that assessed hypertension at low levels of exposure, the OR estimates comparing highest with lowest arsenic exposure groups ranged from 1.17 (95% CI: 0.75, 1.83) in a study in the general U.S. population (Jones et al. 2011) to 2.00 (95% CI: 1.21, 3.31) in a study in central Taiwan (Wang SL et al. 2007).
(Enlarge Image)
Figure 2.
ORs of hypertension by arsenic exposure levels. The area of each square is proportional to the inverse of the variance of the estimated log OR. Horizontal lines represent 95% CIs. In the Chen Y et al. (2007) study, arsenic concentrations in drinking water were estimated based on time-weighted arsenic concentrations (ΣCiTi/ΣTi, where "Ci and Ti denote the well arsenic concentration and drinking duration for the ith well").
The pooled OR of hypertension comparing the highest and lowest arsenic exposure categories in the eight studies with available information on hypertension was 1.27 (95% CI: 1.09, 1.47; p-value for heterogeneity = 0.001; I = 70.2%). The corresponding pooled OR in the five studies with moderate to high arsenic exposure was 1.15 (95% CI: 0.96, 1.37; p-value for heterogeneity = 0.002; I = 76.6%), with the study by Chen Y et al. (2007) being highly influential. Excluding that study, the pooled OR was 2.57 (95% CI: 1.56, 4.24; p-value for heterogeneity = 0.13; I = 46.6%). The pooled OR comparing the highest and lowest arsenic exposure categories in the three studies with low arsenic exposure was 1.56 (95% CI: 1.21, 2.01; p-value for heterogeneity = 0.27; I = 24.6%). We also restricted the overall pooled analysis to studies with multivariable adjusted ORs (pooled OR = 1.22; 95% CI: 1.04, 1.42) (Chen CJ et al. 1995; Chen Y 2007; Jones et al. 2011; Rahman et al. 1999; Zierold et al. 2004), studies with a standard hypertension definition (pooled OR = 1.21; 95% CI: 1.03, 1.42) (Chen CJ et al. 1995; Chen Y 2007; Jones et al. 2011; Rahman et al. 1999; Wang SL et al. 2007), and studies with individual assessment of arsenic exposure (pooled OR = 1.19; 95% CI: 1.02, 1.38) (Chen Y et al. 2007; Jones et al. 2011; Wang SL et al. 2007; Zierold et al. 2004). Funnel plots did not suggest the presence of publication or related biases (data not shown).
We evaluated the dose response for six studies with ORs reported for three or more categories (Figure 3) (Chen CJ et al. 1995; Chen Y 2007; Jones et al. 2011; Rahman et al. 1999; Wang SL et al. 2007; Zierold et al. 2004). Among them, the Chen Y et al. (2007) study in Bangladesh showed no dose–response relationship. Compared with the baseline category, the other study from Bangladesh (Rahman et al. 1999) and the study from Taiwan (Chen CJ et al. 1995) showed increased prevalence of hypertension for most of the arsenic exposure categories. Studies conducted at low levels of exposure in drinking water (Jones et al. 2011; Wang SL et al. 2007; Zierold et al. 2004) showed an increased prevalence of hypertension throughout the range of arsenic exposure levels, although the association was not statistically significant for the intermediate arsenic categories.
(Enlarge Image)
Figure 3.
Evaluation of dose response for arsenic exposure and hypertension. Blue symbols indicate studies conducted in populations with low arsenic levels in drinking water (average < 50 μg/L); black symbols indicate studies conducted in populations with moderate-to-high arsenic levels in drinking water (average > 50 μg/L). The size of each data point is inversely weighted based on the inverse of the variance of the estimated log OR. For the Wang SL et al. (2007) study, actual arsenic levels for each hair tertile were not provided, and values defining the arsenic exposure tertiles were approximated based on the geometric mean of hair arsenic.
For the association of arsenic exposure with BP levels, three of five studies found a positive association with SBP (Dastgiri et al. 2010; Jensen and Hansen 1998; Kwok et al. 2007), and two of four studies found a positive association with DBP (Figure 4) (Dastgiri et al. 2010; Kwok et al. 2007). The difference in BP levels comparing the highest and lowest arsenic exposure categories ranged from –0.79 to 30.0 mmHg for SBP and from –0.65 to 11.04 mmHg for DBP. Only two studies adjusted for hypertension risk factors (Jones et al. 2011; Kwok et al. 2007).
(Enlarge Image)
Figure 4.
Difference (95% CI) in mean SBP and DBP by arsenic exposure level. The area of each square is proportional to the inverse of the variance of the estimated. NA: not available [the study by Chen Y et al. (2007) did not include standard errors or data that would allow estimation of the standard errors for mean systolic and diastolic blood pressure SBP and DBP levels, and a 95% CI could not be calculated for this study]. Professions include taxidermists, garden fence makers, weekend cottage constructors, wood impregnators, electric pylon impregnators, and new house constructors (Jensen and Hansen 1998).
Results
Study Characteristics
Eleven studies, published between 1995 and 2011, were identified (Table 1). All studies meeting the inclusion criteria were cross-sectional and published in English. Combined, the studies covered arsenic exposure and hypertension outcomes for > 20,000 individuals. Eight studies were conducted at moderate to high levels of exposure (average levels in drinking water ≥ 50 μg/L or occupational studies) (Chen CJ et al. 1995; Chen Y 2007; Dastgiri et al. 2010; Guo et al. 2007; Jensen and Hansen 1998; Kwok et al. 2007; Rahman et al. 1999; Yildiz et al. 2008), and three studies were conducted at low levels of exposure (average levels in drinking water < 50 μg/L) (Jones et al. 2011; Wang SL et al. 2007; Zierold et al. 2004). Ten studies were conducted in general populations (two from Taiwan, two from Bangladesh, two from Inner Mongolia, two from the United States, one from Turkey, and one from Iran) (Chen CJ et al. 1995; Chen Y 2007; Dastgiri et al. 2010; Guo et al. 2007; Jones et al. 2011; Kwok et al. 2007; Rahman et al. 1999; Wang SL et al. 2007; Yildiz et al. 2008; Zierold et al. 2004). One study was conducted in an occupational setting in Denmark (Jensen and Hansen 1998). Five studies measured arsenic concentrations in drinking water (Chen CJ et al. 1995; Chen Y 2007; Kwok et al. 2007; Rahman et al. 1999; Zierold et al. 2004), three compared areas of high and low arsenic concentrations in drinking water (Dastgiri et al. 2010; Guo et al. 2007; Yildiz et al. 2008), two studies used biomarkers (hair, Wang SL et al. 2007; urine, Jones et al. 2011), and one study assigned arsenic exposure based on job title (Jensen and Hansen 1998). Eight studies assessed hypertension as the end point of interest (Chen CJ et al. 1995; Chen Y 2007; Guo et al. 2007; Jones et al. 2011; Rahman et al. 1999; Wang SL et al. 2007; Yildiz et al. 2008; Zierold et al. 2004), five studies reported differences in mean SBP (Chen Y et al. 2007; Dastgiri et al. 2010; Jensen and Hansen 1998; Jones et al. 2011; Kwok et al. 2007), and four studies reported differences in mean DBP (Chen Y et al. 2007; Dastgiri et al. 2010; Jones et al. 2011; Kwok et al. 2007).
Quality Assessment
Five studies measured arsenic in drinking water at the individual level (Chen Y et al. 2007; Jones et al. 2011; Kwok et al. 2007; Wang SL et al. 2007; Yildiz et al. 2008); three of these studies measured individual arsenic exposure based on measured well water concentrations (Chen Y et al. 2007; Kwok et al. 2007; Yildiz et al. 2008), and two studies used a biomarker of exposure (Table 2) (Jones et al. 2011; Wang SL et al. 2007). Five studies defined hypertension based on established cutoffs for SBP and DBP levels measured with a standardized protocol and self-reported physician diagnosis or antihypertensive treatment (Chen CJ et al. 1995; Chen Y 2007; Jones et al. 2011; Rahman et al. 1999; Wang SL et al. 2007). Five of the 11 studies did not adjust for potential confounders (Dastgiri et al. 2010; Guo et al. 2007; Jensen and Hansen 1998; Wang SL et al. 2007; Yildiz et al. 2008). Other studies adjusted at least for age, sex, and BMI.
ORs Estimates for Hypertension
For the association of hypertension with arsenic exposure, five of the eight studies found a positive association (Chen CJ et al. 1995; Guo et al. 2007; Rahman et al. 1999; Wang SL et al. 2007; Zierold et al. 2004). Among the studies that assessed hypertension at moderate to high levels of exposure, the OR estimates comparing highest with lowest arsenic exposure groups ranged from 0.71 (95% CI: 0.18, 2.63) in a small study in Turkey (Yildiz et al. 2008) to 16.5 (95% CI: 2.8, 668.5) in a study in Inner Mongolia (Figure 2) (Guo et al. 2007). The two studies from Bangladesh provided inconsistent results: an OR of 3.0 (95% CI: 1.5, 5.8) in the study by Rahman et al. (1999) and an OR of 1.02 (95% CI: 0.84, 1.23) in the study by Chen Y et al. (2007). Among the studies that assessed hypertension at low levels of exposure, the OR estimates comparing highest with lowest arsenic exposure groups ranged from 1.17 (95% CI: 0.75, 1.83) in a study in the general U.S. population (Jones et al. 2011) to 2.00 (95% CI: 1.21, 3.31) in a study in central Taiwan (Wang SL et al. 2007).
(Enlarge Image)
Figure 2.
ORs of hypertension by arsenic exposure levels. The area of each square is proportional to the inverse of the variance of the estimated log OR. Horizontal lines represent 95% CIs. In the Chen Y et al. (2007) study, arsenic concentrations in drinking water were estimated based on time-weighted arsenic concentrations (ΣCiTi/ΣTi, where "Ci and Ti denote the well arsenic concentration and drinking duration for the ith well").
The pooled OR of hypertension comparing the highest and lowest arsenic exposure categories in the eight studies with available information on hypertension was 1.27 (95% CI: 1.09, 1.47; p-value for heterogeneity = 0.001; I = 70.2%). The corresponding pooled OR in the five studies with moderate to high arsenic exposure was 1.15 (95% CI: 0.96, 1.37; p-value for heterogeneity = 0.002; I = 76.6%), with the study by Chen Y et al. (2007) being highly influential. Excluding that study, the pooled OR was 2.57 (95% CI: 1.56, 4.24; p-value for heterogeneity = 0.13; I = 46.6%). The pooled OR comparing the highest and lowest arsenic exposure categories in the three studies with low arsenic exposure was 1.56 (95% CI: 1.21, 2.01; p-value for heterogeneity = 0.27; I = 24.6%). We also restricted the overall pooled analysis to studies with multivariable adjusted ORs (pooled OR = 1.22; 95% CI: 1.04, 1.42) (Chen CJ et al. 1995; Chen Y 2007; Jones et al. 2011; Rahman et al. 1999; Zierold et al. 2004), studies with a standard hypertension definition (pooled OR = 1.21; 95% CI: 1.03, 1.42) (Chen CJ et al. 1995; Chen Y 2007; Jones et al. 2011; Rahman et al. 1999; Wang SL et al. 2007), and studies with individual assessment of arsenic exposure (pooled OR = 1.19; 95% CI: 1.02, 1.38) (Chen Y et al. 2007; Jones et al. 2011; Wang SL et al. 2007; Zierold et al. 2004). Funnel plots did not suggest the presence of publication or related biases (data not shown).
We evaluated the dose response for six studies with ORs reported for three or more categories (Figure 3) (Chen CJ et al. 1995; Chen Y 2007; Jones et al. 2011; Rahman et al. 1999; Wang SL et al. 2007; Zierold et al. 2004). Among them, the Chen Y et al. (2007) study in Bangladesh showed no dose–response relationship. Compared with the baseline category, the other study from Bangladesh (Rahman et al. 1999) and the study from Taiwan (Chen CJ et al. 1995) showed increased prevalence of hypertension for most of the arsenic exposure categories. Studies conducted at low levels of exposure in drinking water (Jones et al. 2011; Wang SL et al. 2007; Zierold et al. 2004) showed an increased prevalence of hypertension throughout the range of arsenic exposure levels, although the association was not statistically significant for the intermediate arsenic categories.
(Enlarge Image)
Figure 3.
Evaluation of dose response for arsenic exposure and hypertension. Blue symbols indicate studies conducted in populations with low arsenic levels in drinking water (average < 50 μg/L); black symbols indicate studies conducted in populations with moderate-to-high arsenic levels in drinking water (average > 50 μg/L). The size of each data point is inversely weighted based on the inverse of the variance of the estimated log OR. For the Wang SL et al. (2007) study, actual arsenic levels for each hair tertile were not provided, and values defining the arsenic exposure tertiles were approximated based on the geometric mean of hair arsenic.
Difference in BP Level Estimates
For the association of arsenic exposure with BP levels, three of five studies found a positive association with SBP (Dastgiri et al. 2010; Jensen and Hansen 1998; Kwok et al. 2007), and two of four studies found a positive association with DBP (Figure 4) (Dastgiri et al. 2010; Kwok et al. 2007). The difference in BP levels comparing the highest and lowest arsenic exposure categories ranged from –0.79 to 30.0 mmHg for SBP and from –0.65 to 11.04 mmHg for DBP. Only two studies adjusted for hypertension risk factors (Jones et al. 2011; Kwok et al. 2007).
(Enlarge Image)
Figure 4.
Difference (95% CI) in mean SBP and DBP by arsenic exposure level. The area of each square is proportional to the inverse of the variance of the estimated. NA: not available [the study by Chen Y et al. (2007) did not include standard errors or data that would allow estimation of the standard errors for mean systolic and diastolic blood pressure SBP and DBP levels, and a 95% CI could not be calculated for this study]. Professions include taxidermists, garden fence makers, weekend cottage constructors, wood impregnators, electric pylon impregnators, and new house constructors (Jensen and Hansen 1998).
Source...