Peripheral Arterial Disease and Its Association With Arsenic Exposure and Metabolism in the Strong Heart Study

Am J Epidemiol. 2016 Dec 1;184(11):806-817. doi: 10.1093/aje/kww002. Epub 2016 Nov 3.

Abstract

At high levels, inorganic arsenic exposure is linked to peripheral arterial disease (PAD) and cardiovascular disease. To our knowledge, no prior study has evaluated the association between low-to-moderate arsenic exposure and incident PAD by ankle brachial index (ABI). We evaluated this relationship in the Strong Heart Study, a large population-based cohort study of American Indian communities. A total of 2,977 and 2,966 PAD-free participants who were aged 45-74 years in 1989-1991 were reexamined in 1993-1995 and 1997-1999, respectively, for incident PAD defined as either ABI <0.9 or ABI >1.4. A total of 286 and 206 incident PAD cases were identified for ABI <0.9 and ABI >1.4, respectively. The sum of inorganic and methylated urinary arsenic species (∑As) at baseline was used as a biomarker of long-term exposure. Comparing the highest tertile of ∑As with the lowest, the adjusted hazard ratios were 0.57 (95% confidence interval (CI): 0.32, 1.01) for ABI <0.9 and 2.24 (95% CI: 1.01, 4.32) for ABI >1.4. Increased arsenic methylation (as percent dimethylarsinate) was associated with a 2-fold increased risk of ABI >1.4 (hazard ratio = 2.04, 95% CI: 1.02, 3.41). Long-term low-to-moderate ∑As and increased arsenic methylation were associated with ABI >1.4 but not with ABI <0.9. Further studies are needed to clarify whether diabetes and enhanced arsenic metabolism increase susceptibility to the vasculotoxic effects of arsenic exposure.

Keywords: arsenic; metabolism; peripheral vascular disease.

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Ankle Brachial Index
  • Antihypertensive Agents / administration & dosage
  • Arizona / epidemiology
  • Arsenic / urine*
  • Biomarkers
  • Blood Pressure
  • Cholesterol, LDL / blood
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / ethnology*
  • Environmental Exposure / adverse effects
  • Female
  • Glomerular Filtration Rate
  • Glycated Hemoglobin A / analysis
  • Humans
  • Hypertension / epidemiology
  • Hypoglycemic Agents / administration & dosage
  • Incidence
  • Indians, North American / statistics & numerical data*
  • Male
  • Menopause
  • Middle Aged
  • Midwestern United States / epidemiology
  • Peripheral Arterial Disease / ethnology*
  • Prospective Studies
  • Risk Factors
  • Sex Factors
  • Smoking / ethnology
  • Socioeconomic Factors

Substances

  • Antihypertensive Agents
  • Biomarkers
  • Cholesterol, LDL
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Arsenic