Table 1
Studies of arsenic exposure and clinical cardiovascular disease outcomes (18 new studies available after 2005 systematic review)
| Study, year | Design | Population | Men (%) | Age Range (yrs) | Arsenic Assessment | Exposed vs. Reference | Endpoint Ascertainment | Outcome (s) | No. of cases/non-cases | Relative Risk | 95 % Confidence Interval | Adjustment Factors |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Taiwan | ||||||||||||
| Liao 2012 [27] | CO (Int) | HAA (3 villages in SW Taiwan) | 43.3 | 35–85 | CEI from village well water levels | >14.7 vs. <17.4 ppm-y | Death Registry | CVD mortality | 10 deaths | 1.89 | 0.50–7.10 | Age, sex, cigarette smoking, hypertension, diabetes, abnormal LDH elevation, Framingham CVD risk score, AST |
| Cheng 2010a [34] | CO (Ext) | HAA (SW & NE Taiwan) | 56 | >35 | Village well water levels | HAA vs. general population | Death registry | Stroke mortality | 8,867 deaths | 1.11 | 1.07–1.14 | Age, sex |
| Wu 2010 [33] | CO (Int) | HAA (NE Taiwan) | 47 | ≥40 | Household well water levels | 50–300 vs. ≤50 μg/L | Death registry | CVD mortality | 22 deaths | 2.07 | 0.74–5.80 | Age, sex, triglyceride, hypertension history, diabetes history, HO-1 genotype, and competing risk of death from malignant neoplasm or other specified causes |
| Tseng 2005b [24] | CS | HAA (3 villages in SW Taiwan) | 45 | ≥30 | Urine total arsenic & CEI from village well water | >64.33 μg/L urine vs. 0 mg/L-y CEI | ABI | PAD prevalence | 54/425 | 3.84 | 0.86–17.25 | Age, sex, BMI, alcohol drinking, cholesterol |
| Horng & Lin 1997a [35] | CC | HAA | 53 | NR | Urine total arsenic | >75th vs. <25th p (15.3 μg/L vs. 5.1 μg/L) | Blackfoot disease patients | BFD prevalence | 32/32 | 1.85 | 1.43–2.40 | — |
| Other high exposure areas (Bangladesh, Chile, Inner Mongolia, and Pakistan) | ||||||||||||
| Chen 2011 [28••] | CO (Int) | Araihazar, Bangladesh | NR | 18–75 | Baseline individual well water levels | >80th vs. <20th p (mean 266 μg/L vs. mean 3.7 μg/L) | Verbal autopsy, medical records | CVD mortality | 106 deaths | 1.46 | 0.96–2.20 | Age, sex, education, BMI, smoking status |
| CHD mortality | 40 deaths | 1.94 | 0.99–3.84 | |||||||||
| Stroke mortality | 41 deaths | 1.07 | 0.54–2.12 | |||||||||
| Baseline urine total arsenic levels (μg/g creatinine) | >80th vs. <20th p (mean 642 μg/g vs. mean 69 μg/g) | CVD mortality | 90 deaths | 1.55 | 1.01–2.37 | |||||||
| CHD mortality | 34 deaths | 1.90 | 0.91–3.98 | |||||||||
| Stroke mortality | 35 deaths | 1.03 | 0.53–2.03 | |||||||||
| Khan 2010a [36] | CS | 1 village in Bangladesh | 50 | ≥30 | Village drinking water levels | >50 μg/L w/arsenicosis vs. <50 μg/L w/out arsenicosis | ABI | PAD prevalence | 19/221 | 5.8 | 1.26–26.85 | Age, sex, smoking, BMI, diabetes, blood pressure status |
| Sohel 2009 [29•] | CO (Int) | Matlab, Bangladesh | 50 | ≥15 | Household well levels | >300 vs. <10 μg/L | Verbal autopsy | CVD mortality | 281 deaths | 1.37 | 1.07–1.77 | Age, sex, education, asset score (SES) |
| Yuan 2007a [37] | CO (Ext) | Regions of Chile in 1958–1970 (peak arsenic exposure in Region II) | NR | ≥20 | Approximate population- weighted drinking water levels | Region II vs. Region V | Death certificate | CVD mortality | 6,164 deaths | 1.01 | 0.88–1.17 | Age, sex |
| CHD mortality | 2,196 deaths | 1.23 | 1.00–1.45 | |||||||||
| Stroke mortality | 1,624 deaths | 0.89 | 0.78–1.00 | |||||||||
| PAD mortality | 790 deaths | 1.03 | 0.84–1.21 | |||||||||
| Wade 2009c [30] | CO (Int) | Inner Mongolia (1 village) | 50 | 0–>80 | Household, shared, or community well levels | >300 vs. <5 μg/L | Verbal autopsy & medical record review | CVD mortality | 152 deaths | 2.47 | 0.50–12.18 | Age, sex, education, smoking, drinking, and farm work |
| Stroke mortality | 54 deaths | 1.02 | 0.16–6.71 | |||||||||
| Xia 2009a [38] | CS | Inner Mongolia (1 village) | 50 | 0 – >80 | Household well levels | >300 vs. <5 μg/L | Self-report | CVD prevalence | 269/3,038 | 1.72 | 0.81–3.67 | Age, sex, education, smoking, household income, water source type, alcohol consumption |
| Per 50 μg/L increase | Stroke prevalence | 127/12,207 | 1.03 | 0.93–1.15 | ||||||||
| Afridi 2010, 2011a,d [39,40] | CC | Hyderabad, Pakistan | 57 | 45–60 | Scalp hair total arsenic levels | 75th vs. 25th p (1.28 μg/g vs. 1.14 μg/g)e | Coronary angiogram and at least one positive test of MI (stress text or echocardiography) | MI incidence | 58/61 | 3.41 | 1.67–6.99 | Age, SES |
| Urine total arsenic levels | 75th vs. 25th p (6.06 μg/L vs. 3.66 μg/L)f | 58/61 | 6.62 | 2.05–21.33 | ||||||||
| Low to moderate exposure areas (U.S., Spain, Slovakia, Japan) | ||||||||||||
| Gong & O’Bryant 2012a [41] | CS | 3 rural counties (Texas, U.S.) | 31 | 40–96 | Estimated residential drinking water levels | 75th vs. 25th p (8.1 μg/L vs. 4.1 μg/L) | Self-reported physician diagnosis | CHD prevalence | 69/430 | 1.46 | 1.39–1.53 | AS3MT genotype, ethnicity, age, gender, education, smoking, use of antihypertensive meds, alcoholism |
| Lisabeth 2010f [31•] | CO (Int) | 27 zip codes in Genesee county (Michigan, U.S.) | 50 | ≥ 45 | Population-weighted average zip code drinking water levels | 80th vs. 20th p (19–22.3 μg/L vs. 0.3–<4.5 μg/L) | Hospital inpatient database | Ischemic stroke hospitalizations | 14,033 admissions | 2.74 | 1.66–4.53 | Age, sex, income, race |
| Medrano 2010 [32•] | CO (Ext) | 651 municipalities in Spain | NR | >20 | Municipal drinking water levels | >10 vs. < 1 μg/L | Death certificate | CVD mortality | 158,419 deaths | 1.03 | 0.98–1.08 | Sex, age and the following provincial level variables: income, hospital beds, CV risk factors, dietary factors, and water characteristics |
| CHD mortality | 50,244 deaths | 1.05 | 0.95–1.08 | |||||||||
| Stroke mortality | 42,164 deaths | 1.07 | 0.95–1.09 | |||||||||
| Rapant 2009a [42] | CO (Ext) | 1 region in Slovakiag | NR | NR | Mean groundwater levels | Exposed region vs. general population | Death certificate | CVD mortality | NR | 1.08 | NR | — |
| Yoshikaw a 2008a [43] | CO (Ext) | 264 municipalities in Japan | 47 | NR | 5-year average municipal environmental air levels | >90th vs. ≤10th p (≥2.70 ng/m3 vs. <0.77 ng/m3) | National health maps | CVD mortality | 14,247 deaths | 1.03 | 0.99–1.06 | Age, sex |
| Stroke mortality | 13,596 deaths | 1.02 | 0.98–1.05 | |||||||||
| Meliker 2007a [44] | CO (Ext) | 6 counties (Michigan, U.S.) | NR | ≥35 | Population-weighted county drinking water levels | 6 counties vs. general population | Death certificate | CVD mortality | 52,606 deaths | 1.13 | 1.11–1.15 | Age, sex, race |
| CHD mortality | 26,646 deaths | 1.01 | 0.99–1.03 | |||||||||
| Stroke mortality | 8,503 deaths | 1.19 | 1.16–1.23 | |||||||||
| PAD mortality | 2,549 deaths | 1.03 | 0.97–1.08 | |||||||||
ABI: ankle-brachial blood pressure index; AST: aspartate aminotransferase; BMI: body mass index; CABG: coronary artery bypass graft surgery; CBVD: cerebrovascular disease; CC: case-control; CEI: cumulative exposure index = Σ arsenic levels in drinking water × time of exposure (i: specific village); CI: confidence interval; CO: cohort; CS: cross-sectional; CV: cardiovascular; DAAC: diseases of the arteries, arterioles, and capillaries; ECG: electrocardiogram; Ext.: external comparisons; HAA: High arsenic area; Int.: internal comparisons; LDH: lactate dehydrogenase; MI: myocardial infarction; NR: not reported; PAD: peripheral arterial disease; PCI: percutaneous coronary intervention; p: percentile; RR: relative risk; SES: socioeconomic status.
aRR and/or 95 % CI derived using the results reported in the original study.
bTseng et al. 2005 [24] presented results from the same subjects as Tseng et al. 1996 [25], which was included in the previous systematic review by Navas–Acien et al. (2005) [6]. However, Tseng et al. 2005 presents a new analysis of PAD prevalence associated with urine total arsenic.
cSubset of residents exposed since 1990.
dOnly including subjects with their first MI.
eWeighted average of 75th and 25th percentiles, by number of cases.
fThe Genesee zip code analysis was selected over results from the entire state of Michigan; Genesee county has the highest levels of exposure and the results were presented in quintiles of exposure.
gSpišsko–Gemerské rudohorie Mountains (mean arsenic levels in drinking water: 13 μg/L)