Chronic arsenic exposure and risk of carotid artery disease: The Strong Heart Study

Abstract

Background Inorganic arsenic exposure from naturally contaminated groundwater is related to vascular disease. No prospective studies have evaluated the association between arsenic and carotid atherosclerosis at low-moderate levels. We examined the association of long-term, low-to-moderate inorganic arsenic exposure with carotid arterial disease. Methods American Indians, 45 to 74 years old, in Arizona, Oklahoma, and North and South Dakota had arsenic concentrations (sum of inorganic and methylated species, μg/g urine creatinine) measured from baseline urine samples (1989-1991). Carotid artery ultrasound was performed in 1998-1999. Vascular disease was assessed by the carotid intima media thickness (CIMT), the presence of atherosclerotic plaque in the carotid, and by the number of segments containing plaque (plaque score). Results 2402 participants (mean age 55.3 years, 63.1% female, mean body mass index 31.0kg/m2, diabetes 45.7%, hypertension 34.2%) had a median (interquintile range) urine arsenic concentration of 9.2 (5.00, 17.06) μg/g creatinine. The mean CIMT was 0.75 mm. 64.7% had carotid artery plaque (3% with >50% stenosis). In fully adjusted models comparing participants in the 80th vs. 20th percentile in arsenic concentrations, the mean difference in CIMT was 0.01 (95% confidence interval (95%CI): 0.00, 0.02) mm, the relative risk of plaque presence was 1.04 (95%CI: 0.99, 1.09), and the geometric mean ratio of plaque score was 1.05 (95%CI: 1.01, 1.09). Conclusions Urine arsenic was positively associated with CIMT and increased plaque score later in life although the association was small. The relationship between urinary arsenic and the presence of plaque was not statistically significant when adjusted for other risk factors. Arsenic exposure may play a role in increasing the severity of carotid vascular disease.

Positive Association of Cardiovascular Disease (CVD) with Chronic Exposure to Drinking Water Arsenic (As) at Concentrations below the WHO Provisional Guideline Value: A Systematic Review and Meta-analysis

“…We found the linear model better using AIC as the selection criteria depicting the associations of low-level As concentration and CVD outcomes. Such a conclusion has already been confirmed by several epidemiological and biological studies [36,53,61]. However, it has been illustrated that several mechanisms of As toxicity, ranging from the generation of oxidative stress, inhibition of DNA repair to modulation of signal transduction pathways and perturbation of DNA methylation patterns, are likely to give rise to nonlinear dose-response relationships, especially at low concentrations [98,99].…”

“…Furthermore, as it is difficult to convert plasma As to water As, we excluded two studies which could only provide plasma As concentration to lower the bias of exposure assessment [50,51]. In addition, as there was only one study analysing each of soluble E-selectin, myeloperoxidase, plasminogen activator inhibitor-1 (PAI-1), soluble Intercellular Adhesion Molecule 1 (ICAM-1) and soluble Vascular cell adhesion protein 1 (VCAM-1) [18], carotid atherosclerosis indices (CAIs) [52], common carotid intima media thickness, plaque score and the presence of plaque in the common carotid [53], peripheral vascular disease [54,55] as well as some other CVD subtypes and clinic markers [21,27,[56][57][58][59][60][61], respectively, these variables have not been included in our dose-response meta-analysis. Moreover, due to the fact that significant differences could be found regarding concentrations of matrix-metalloproteases (MMPs) using plasma vs. serum [62], we further excluded two studies which analysed the plasma MMPs and serum MMPs respectively to avoid bias in outcome ascertainment [18,21] ( Figure S1).…”

Heavy Metal-Induced Cerebral Small Vessel Disease: Insights into Molecular Mechanisms and Possible Reversal Strategies

“…A high level of monomethylarsonic acid has been reported with a significantly high occurrence of ischemic stroke incidence [146]. The Strong Heart Study, and other cohort studies, have demonstrated that low-to-moderate exposure to inorganic arsenic is positively associated with high occurrence of plaques and an increase in the thickness of carotid intima-media [147,148]. In these studies, higher levels of arsenic metabolite monomethylarsonic acid have been observed with increased carotid intima-media thickness.…”

Arsenic and the immune system

“…Chronic inflammation and secretion of growth factors, such as IL-8, can also establish microenvironments supportive of tumor development [54]. Epidemiological studies carried out in various countries demonstrate that arsenic significantly increases the risk of atherosclerosis [55,56]. Several mechanisms may contribute to the development of atherosclerosis, including general pro-inflammatory cytokine secretion [10], increased ROS production [8], enhanced monocyte adhesion to vascular endothelium [57] and reduced cholesterol efflux from macrophages [7].…”