Associations of Toenail Arsenic, Cadmium, Mercury, Manganese, and Lead with Blood Pressure in the Normative Aging Study

By Mordukhovick, Irina; Wright, Robert O. et al. | Environmental Health Perspectives, January 2012 | Go to article overview

Associations of Toenail Arsenic, Cadmium, Mercury, Manganese, and Lead with Blood Pressure in the Normative Aging Study


Mordukhovick, Irina, Wright, Robert O., Hu, Howard, Amarasiriwardena, Chitra, Baccarelli, Andrea, Litonjua, Augusto, Sparrow, David, Vokonas, Pantel, Schwartz, Joel, Environmental Health Perspectives


BACKGROUND: Arsenic, cadmium, mercury, and lead are associated with cardiovascular disease in epidemiologic research. These associations may be mediated by direct effects of the metals on blood pressure (BP) elevation. Manganese is associated with cardiovascular dysfunction and hypotension in occupational cohorts.

OBJECTIVES: We hypothesized that chronic arsenic, cadmium, mercury, and lead exposures elevate BP and that manganese lowers BP.

METHODS: We conducted a cross-sectional analysis of associations between toenail metals and BP among older men from the Normative Aging Study (n = 639), using linear regression and adjusting for potential confounders.

RESULTS: An interquartile range increase in toenail arsenic was associated with higher systolic BP [0.93 mmHg; 95% confidence interval (CI): 0.25, 1.62] and pulse pressure (0.76 mmHg; 95% CI: 0.22, 1.30). Positive associations between arsenic and BP and negative associations between manganese and BP were strengthened in models adjusted for other toenail metals.

CONCLUSIONS: Our findings suggest associations between BP and arsenic and manganese. This may be of public health importance because of prevalence of both metal exposure and cardiovascular disease. Results should be interpreted cautiously given potential limitations of toenails as biomarkers of metal exposure.

KEY WORDS: arsenic, blood pressure, cadmium, epidemiology, lead, manganese, mercury, metals. Environ Health Perspect 120:98-104 (2012). http://dx.doi.org/10.1289/ehp.1002805 [Online 30 August 2011]

Arsenic, cadmium, mercury, and lead are associated with cardiovascular disease in epidemiologic research (Engel et al. 1994; Houston 2007; Navas-Acien et al. 2007). These associations may be mediated by direct effects on blood pressure (BP) elevation. In animals, arsenic, cadmium, mercury, and lead induce hypertension (Navas-Acien et al. 2007; Satarug et al. 2006; Wakita 1987; Yang et al. 2007), and manganese causes hypotension (Jiang and Zheng 2005). All five metals are plausibly linked with BP, based on mechanistic and experimental data (Houston 2007; Jiang and Zheng 2005; Navas-Acien et al. 2007; Valkoet al. 2005).

Epidemiologic studies show consistent associations between high arsenic exposure and BP (Chen et al. 1995; Rahman et al. 1999). Few studies have assessed lower-level exposure. Research on cadmium and BP is inconsistent (Staessen et al. 2000; Tellez-Plaza et al. 2008). Lead is a known risk factor for BP elevation (Navas-Acien et al. 2007), but no studies have evaluated toenail lead. High manganese exposure is associated with cardiovascular dvsfunction and hypotension in occupational cohorts (Jiang and Zheng 2005). Research at lower exposures is inconsistent (Gonzalez-Munoz et al. 2010; Taneja and Mandal 2007). Studies examining mercury and BP report mixed results (Johansson et at, 2002; Pedersen et al. 2005; Valera et al. 2009). Data on low-level mercury are sparse.

We hypothesized that chronic arsenic, cadmium, mercury, and lead exposures elevate BP and that manganese lowers BP. We evaluated these hypotheses in a cohort of elderly men from the Greater Boston area.

Materials and Methods

Study population. Subjects are from the ongoing, longitudinal Veterans Administration Normative Aging Study (NAS) (Bell et al. 1972). Participants are males with no known chronic medical conditions at recruitment. They are evaluated at study visits every 3-5 years, ihis study has been approved by all relevant institutional review boards. All participants gave their written informed consent.

We asked NAS participants to bring toenail clippings to their study visit between January 1999 and January 2009 (n = 818 eligible NAS participants). For our analysis, we excluded NAS participants who did not bring toenail clippings (n = 165) or were missing information on BP (n = 3), race/ethnicity (n = 12), education (n = 22), alcohol intake (n =11), age (n = 1), body mass index (BMI; n = 1), smoking history (m = 1), pack-years (n = 1), or season of clinical visit (n = 1). …

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