Hung Yi Chiou

Dose-Response Relationship Between Ischemic Heart Disease Mortality and Long-term Arsenic Exposure

The cardiovascular effects of inorganic arsenic have been documented, but the dose-response relationship between ischemic heart disease (ISHD) and long-term arsenic exposure remains to be elucidated. Mortality rates from ISHD among residents in 60 villages of the area in Taiwan with endemic arseniasis from 1973 through 1986 were analyzed to examine their association with arsenic concentration in drinking water. Based on 1 355 915 person-years and 217 ISHD deaths, the cumulative ISHD mortalities from birth to age 79 years were 3.4%, 3.5%, 4.7%, and 6.6%, respectively, for residents who lived in villages in which the median arsenic concentrations in drinking water were <0.1, 0.1 to 0.34, 0.35 to 0.59, and > or = 0.6 mg/L. A cohort of 263 patients affected with blackfoot disease (BFD), a unique arsenic-related peripheral vascular disease, and 2293 non-BFD residents in the endemic area of arseniasis were recruited and followed up for an average period of 5.0 years. There was a monotonous biological gradient relationship between cumulative arsenic exposure through drinking artesian well water and ISHD mortality. The relative risks were 2.5, 4.0 and 6.5, respectively, for those who had a cumulative arsenic exposure of 0.1 to 9.9, 10.0 to 19.9, and > or = 20.0 mg/L-years compared with those without the arsenic exposure after adjustment for age, sex, cigarette smoking, body mass index, serum cholesterol and triglyceride levels, and disease status for hypertension and diabetes through proportional-hazards regression analysis. BFD patients were found to have a significantly higher ISHD mortality that non-BFD residents, showing a multivariate-adjusted relative risk of 2.5 (95% CI, 1.1 to 5.4).

Dose-Response Relationship Between Prevalence of Cerebrovascular Disease and Ingested Inorganic Arsenic

BACKGROUND AND PURPOSE Circulatory diseases such as ischemic heart disease and peripheral vascular disease induced by long-term arsenic exposure have been well documented in previous studies, but the dose-response relationship between cerebrovascular disease and ingested inorganic arsenic remains to be elucidated. The prevalence of cerebrovascular disease among residents of the Lanyang Basin on the northeast coast of Taiwan was surveyed to examine its association with exposure to arsenic in well water. METHODS A total of 8102 men and women from 3901 households were recruited in this study. The status of cerebrovascular disease of study subjects was identified through home-visit personal interviews and ascertained by review of hospital medical records according to the World Health Organization criteria. Information on consumption of well water, sociodemographic characteristics, cigarette smoking, and alcohol consumption habits, as well as personal and family history of diseases, was also obtained. Arsenic concentration in the well water of each household was determined by hydride generation and atomic absorption spectrometry. Logistic regression analysis was used to estimate multivariate-adjusted odds ratios and 95% confidence intervals for various risk factors of cerebrovascular disease. RESULTS A significant dose-response relationship was observed between arsenic concentration in well water and prevalence of cerebrovascular disease after adjustment for age, sex, hypertension, diabetes mellitus, cigarette smoking, and alcohol consumption. The biological gradient was even more prominent for cerebral infarction, showing multivariate-adjusted odds ratios of 1.0, 3.4, 4.5, and 6.9, respectively, for those who consumed well water with an arsenic content of 0, 0.1 to 50.0, 50.1 to 299.9, and > 300 micrograms/L. CONCLUSIONS Long-term exposure to inorganic arsenic from well water was associated with an increased prevalence of cerebrovascular disease, especially cerebral infarction.

Biological Gradient Between Long-Term Arsenic Exposure and Carotid Atherosclerosis

Background—Long-term exposure to ingested arsenic has been documented to induce peripheral vascular disease, ischemic heart disease, and cerebral infarction in a dose-response relationship. This study further examined the biological gradient between ingested inorganic arsenic and carotid atherosclerosis. Methods and Results—We studied 199 male and 264 female adult residents from the southwestern area of endemic arseniasis in Taiwan. The extent of carotid atherosclerosis was assessed by duplex ultrasonography. Diabetes mellitus was determined by oral glucose tolerance test, hypertension by mercury sphygmomanometers, and serum lipid profiles by autoanalyzers. Information regarding the consumption of high-arsenic artesian well water, cigarette smoking, and alcohol consumption was obtained through standardized questionnaire interviews. Logistic regression analysis was used to estimate the odds ratio and its 95% CI of carotid atherosclerosis for various risk factors. Three indices of long-term exposure to ingested arsenic, including the duration of consuming artesian well water, the average arsenic concentration in consumed artesian well water, and cumulative arsenic exposure, were all significantly associated with prevalence of carotid atherosclerosis in a dose-response relationship. The biological gradient remained significant after adjustment for age, sex, hypertension, diabetes mellitus, cigarette smoking, alcohol consumption, waist-to-hip ratio, and serum levels of total cholesterol and LDL cholesterol. The multivariate-adjusted odds ratio was 3.1 (95% CI 1.3 to 7.4) for those who had a cumulative arsenic exposure of ≥20 mg/L-years compared with those without exposure to arsenic from drinking artesian well water. Conclusions—Carotid atherosclerosis is associated with ingested inorganic arsenic, showing a significant biological gradient.

Long-term arsenic exposure and ischemic heart disease in arseniasis-hyperendemic villages in Taiwan.

The association between long-term arsenic exposure and peripheral vascular disease has been well documented in our previous epidemiologic studies. The purpose of this study was to evaluate whether long-term arsenic exposure could be associated with ischemic heart disease (IHD). A total of 462 subjects living in the blackfoot disease-hyperendemic villages along the southwestern coast of Taiwan and characterized by long-term arsenic exposure from drinking artesian well water was studied. The subjects were recruited from an epidemiologic cohort who participated in a health examination. IHD was diagnosed by coding the resting electrocardiograms with the Minnesota code. History of arsenic exposure was estimated through information obtained from a personal interview according to a structured questionnaire and the arsenic content in artesian well water of the villages. Cumulative arsenic exposure (CAE) was calculated as the sum of the products multiplying the arsenic concentration in artesian well water (mg/l) by the duration of drinking the water (years) in consecutive periods of living in the different villages. Among the subjects, 78 cases (16.9%) were diagnosed as having IHD. The prevalence rates of IHD for the age groups of 30-39, 40-49, 50-59, and >/=60 years were 4.9, 7.5, 16.8, and 30.7%, respectively (P<0.001). For those with CAE of 0, 0.1-14.9 and >/=15 mg/l-years, the prevalence rates of IHD were 5.2, 10.9 and 24.1%, respectively (P<0.001). The odds ratios (95% confidence intervals) for IHD were 1.60 (0.48, 5.34), and 3.60 (1.11, 11.65), respectively, for those with CAE of 0.1-14.9 and >/=15.0 mg/l-years, when compared with those lacking drinking water exposure to arsenic after multivariate adjustment. It is concluded that IHD in the arseniasis-hyperendemic villages in Taiwan was associated with long-term arsenic exposure.

Get With The Guidelines-Stroke Performance Indicators: Surveillance of Stroke Care in the Taiwan Stroke Registry: Get With The Guidelines-Stroke in Taiwan

Background— Stroke is a leading cause of death around the world. Improving the quality of stroke care is a global priority, despite the diverse healthcare economies across nations. The American Heart Association/American Stroke Association Get With the Guidelines-Stroke program (GWTG-Stroke) has improved the quality of stroke care in 790 US academic and community hospitals, with broad implications for the rest of the country. The generalizability of GWTG-Stroke across national and economic boundaries remains to be tested. The Taiwan Stroke Registry, with 30 599 stroke admissions between 2006 and 2008, was used to assess the applicability of GWTG-Stroke in Taiwan, which spends ≈1/10 of what the United States does in medical costs per new or recurrent stroke. Methods and Results— Taiwan Stroke Registry, sponsored by the Taiwan Department of Health, engages 39 academic and community hospitals and covers the entire country with 4 steps of quality control to ensure the reliability of entered data. Five GWTG-Stroke performance measures and 1 safety indicator are applicable to assess Taiwan Stroke Registry quality of stroke care. Demographic and outcome figures are comparable between GWTG-Stroke and Taiwan Stroke Registry. Two indicators (early and discharge antithrombotics) are close to GWTG-Stroke standards, while 3 other indicators (intravenous tissue plasminogen activator, anticoagulation for atrial fibrillation, lipid-lowering medication) and 1 safety indicator fall behind. Preliminary analysis shows that compliance with selected GWTG-Stroke guidelines is associated with better outcomes. Conclusions— Results suggest that GWTG-Stroke performance measures, with modification for ethnic factors, can become global standards across national and economic boundaries for assessing and improving quality of stroke care and outcomes. GWTG-Stroke can be incorporated into ongoing stroke registries across nations.

Epidemiologic evidence of diabetogenic effect of arsenic

It is well documented that arsenic can lead to skin lesions, atherosclerotic diseases and cancers. The association between arsenic exposure and diabetes mellitus is a relatively new finding. Up to now, there are six epidemiologic reports linking diabetes mellitus with arsenic exposure from environmental and occupational sources. Two reports in Taiwan carried out in the blackfoot disease-hyperendemic villages, one cross-sectional and one prospective follow-up of the same cohort, indicate that arsenic exposure from drinking artesian well water is associated with prevalence and incidence of diabetes mellitus in a dose-responsive pattern. The observation of the relation between arsenic exposure and diabetes mellitus is further supported by studies carried out in Sweden and Bangladesh. In Sweden, case-control analyses of death records of copper smelters and glass workers revealed a trend of increasing diabetes mellitus with increasing arsenic exposure from inhalation. In Bangladesh, prevalence of diabetes mellitus among arsenic-exposed subjects with keratosis was about five times higher than unexposed subjects. Increasing trends of diabetes mellitus with indices of arsenic exposure in drinking water seems to be independent of the presence of skin lesions associated with arsenic exposure. Although these studies consistently show an association between arsenic exposure and diabetes mellitus, the weak study designs of cross-sectional or case-control, the use of glucosuria or diabetes death as diagnostic criteria and the lack of adjustment for possible confounders in some studies, are major limitations that may reduce the strength of the evidence.

Low serum carotene level and increased risk of ischemic heart disease related to long-term arsenic exposure

To elucidate the association between arsenic-related ischemic heart disease (ISHD) and serum antioxidant micronutrient level, residents aged 30 or older living in arseniasis-hyperendemic villages in Taiwan were recruited in a community-based health survey. A structured questionnaire was used to obtain a history of long-term exposure to arsenic through consuming artesian well water and fasting serum samples were also collected at the recruitment. A total of 74 patients affected with ISHD, who were diagnosed through both electrocardiography and Rose questionnaire interview, and 193 age-sex-matched healthy controls were selected for the examination of serum levels of micronutrients by high performance liquid chromatography (HPLC). There was a significant biological gradient between the risk of ISHD and the duration of consuming high-arsenic artesian well water. A significant reverse dose-response relationship with arsenic-related ISHD was observed for serum level of alpha- and beta-carotene, but not for serum levels of retinol, lycopene and alpha-tocopherol. Multivariate analysis showed a synergistic interaction on arsenic-related ISHD between duration of consuming artesian well water and low serum carotene level. An increased risk of arsenic-related ISHD was also associated with hypertension and elevated body mass index, but not with serum lipid profile, cigarette smoking and alcohol drinking. The findings seem to suggest that arsenic-related ISHD has a pathogenic mechanism which is at least partially different from that of ISHD unrelated to long-term exposure to arsenic.

Association between genetic variant on chromosome 12p13 and stroke survival and recurrence: a one year prospective study in Taiwan

BackgroundThe association between ischemic stroke and 2 single nucleotide polymorphisms (SNPs) on chromosome 12p13, rs12425791 and rs11833579 appears inconsistent across different samples. These SNPs are close to the ninjurin2 gene which may alter the risk of stroke by affecting brain response to ischemic injury. The purpose of this study was to investigate the association between these two SNPs and ischemic stroke risk, as well as prognostic outcomes in a Taiwanese sample.MethodsWe examined the relations of these two SNPs to the odds of new-onset ischemic stroke, ischemic stroke subtypes, and to the one year risk of stroke-related death or recurrent stroke following initial stroke in a case-control study. A total of 765 consecutive patients who had first-ever ischemic stroke were compared to 977 stroke-free, age-matched controls. SNPs were genotyped by Taqman fluorescent allelic discrimination assay. The association between ischemic stroke and SNPs were analyzed by multivariate logistic regression. Cox proportional hazard model was used to assess the effect of individual SNPs on stroke-related mortality or recurrent stroke.ResultsThere was no significant association between SNP rs12425791 and rs11833579 and ischemic stroke after multiple testing corrections. However, the marginal significant association was observed between SNP rs12425791 and large artery atherosclerosis under recessive model (OR, 2.30; 95%CI, 1.22-4.34; q-value = 0.062). Among the 765 ischemic stroke patients, 59 died or developed a recurrent stroke. After adjustment for age, sex, vascular risk factors and baseline stroke severity, Cox proportional hazard analysis indicated that the hazard ratios were 2.76 (95%CI, 1.34-5.68; q-value, 0.02) and 2.15 (95%CI, 1.15-4.02; q-value, 0.03) for individuals with homozygous variant allele of rs12425791 and rs11833579, respectively.ConclusionsThis is a precedent study that found genetic variants of rs12425791 and rs11833579 on chromosome 12p13 are independent predictors of stroke-related mortality or stroke recurrence in patients with incident ischemic stroke in Taiwan. Further study is needed to explore the details of the physiological function and the molecular mechanisms underlying the association of this genetic locus with ischemic stroke.

Arsenic in Drinking Water and Risk of Urinary Tract Cancer: A Follow-up Study from Northeastern Taiwan

The evidence linking arsenic in drinking water with increased urinary cancer risk comes from populations in relatively high exposure areas (>100 μg/L), whereas studies from lower exposure areas (<100 μg/L) reported inconsistent results. A previous study conducted in northeastern Taiwan, where residents were exposed to relatively lower concentrations, reported increased risk of urinary cancer in a dose-response way. Using the same cohort with longer follow-up, we conducted analysis to elucidate the relationship between ingested arsenic and urinary cancer in lower exposure groups and assessed the influence of duration, recency, and latency of drinking arsenic-containing well water. A total of 8,086 residents from northeastern Taiwan were followed for 12 years. Incident urinary cancer was ascertained through linkage with the national cancer registry. All analysis was done by Cox proportional hazards regression models. There were 45 incidences of urinary cancer and a monotonic increased risk of urinary cancer was found with increasing arsenic concentration (P < 0.001). For the highly exposed (>100 μg/L), the relative risks (RR) were >5-fold, whereas the risk was elevated but not significant for low exposure (<100 μg/L). Relative to the arsenic concentration <10 μg/L, those who drank well water with higher concentration from birth [RR, 3.69; 95% confidence interval (95% CI), 1.31-10.4], still drank at enrollment (RR, 3.50; 95% CI, 1.33-9.22), and drank for >50 years (RR, 4.12; 95% CI, 1.48-11.5) had a significantly increased risk of urinary cancer. When restricted to urothelial carcinoma, all risk estimates including concentration and characteristics of well water consumption were higher. Cancer Epidemiol Biomarkers Prev; 19(1); 101–10

Determinants of inorganic arsenic methylation capability among residents of the Lanyang Basin, Taiwan: arsenic and selenium exposure and alcohol consumption

The objective of this study was to assess individual variation in inorganic arsenic methylation capability and the association between selenium levels in urine and blood, and inorganic arsenic methylation capability among residents of the Lanyang Basin who drank groundwater and were exposed to high concentrations of inorganic arsenic. According to the arsenic concentration of their drinking water, they were equally and randomly classified into four groups of 252 persons. It turned out that the higher the concentration of arsenic in well water was and thus the cumulative arsenic exposure, the higher the total inorganic arsenic metabolites in urine (total As(i)) and the overall inorganic and organic arsenic in urine (overall As(i+o)) were. The percentage of inorganic arsenic significantly decreased and the DMA percentage significantly increased as the concentration of urinary selenium and serum alpha-tocopherol increased. It appeared that urinary selenium levels increased the metabolism by methylation of arsenic, a finding that requires further investigation.