Low-level lead exposure, metabolic syndrome, and heart rate variability: the VA Normative Aging Study.

Exposure to lead is known to affect the cardiovascular system, even at low, general environmental levels. Many epidemiologic studies have shown an association between chronic low-level lead exposure and hypertension (Hu et al. 1996; Korrick et al. 1999; Nash et al. 2003) and cardiovascular disease (Cheng et al. 1998; Lustberg and Silbergeld 2002; Schwartz 1991). One possible mechanism for this association is interference in autonomic nerve control of the heart. Experimental studies have shown that lead can generate reactive oxygen species (ROS) by depletion of glutathione and protein-bound sulfhydryl groups, leading to oxidative stress (Gurer and Ercal 2000). Oxidative stress plays an important role in the production of proinflammatory mediators, lipid peroxidation, the suppression of nitric oxide, and alteration of calcium homeostasis, which may increase central sympathetic nerve activity and reduce baroreflex sensitivity and vagal parasympathetic tone (Ding et al. 2000; Dursun et al. 2005; Vaziri 2002). Heart rate variability (HRV) is a non-invasive and quantitative marker of cardiac autonomic function that reflects the regulation of the sinoatrial node by the sympathetic and parasympathetic branches of the autonomic nervous system [Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology (Task Force) 1996]. Decreased HRV is an independent predictor of mortality in middle-aged and elderly subjects, in patients with diabetes, and in survivors of myocardial infarction and other coronary heart diseases (Gerritsen et al. 2001; Tapanainen et al. 2002; Tsuji et al. 1996). Several studies of workers occupationally exposed to lead support the contention that lead acts upon the heart via the autonomic nervous system (Bockelmann et al. 2002; Murata and Araki 1991; Murata et al. 1993; Teruya et al. 1991). A recent study from Korea on subjects nonoccupationally exposed to lead showed significant univariate associations between blood lead and HRV measures, but failed to find the associations after adjustment for confounding variables, such as age, alcohol consumption, and other blood metal concentrations (Jhun et al. 2005). In a community-based study of the relationship between bone lead and cardiac conduction among elderly men environmentally exposed to lead, our group previously found that higher bone lead levels were associated with electrocardiographic (ECG) features such as longer QT and QRS intervals and intra-ventricular and atrioventricular conduction defects, suggesting depressed cardiac conduction (Cheng et al. 1998). This could be evidence that even low-level exposure to lead may alter autonomic activity, because cardiac conduction is mediated, in part, through a branch of the autonomic nervous system (Ahnve and Vallin 1982). Another issue in the study of lead toxicity is the identification of susceptible population groups, such as those with preexisting cardiovascular conditions. For example, people with metabolic syndrome (MetS), a cluster of health risks including obesity, diabetes, hypertension, and dyslipidemia (Moller and Kaufman 2005), are at greater risk of cardiovascular disease because they are likely to have stronger levels of oxidative-stress–induced inflammatory responses. As a result, they may be less able to homeostatically control responses to additional oxidative stressors such as lead exposure and therefore show more pronounced responses. Recently, Tsaih et al. (2004) observed that lead had a more pronounced effect on renal function in people with diabetes and hypertension. However, to our knowledge, no previous study has examined modifications of the association between lead exposure and HRV by clinical conditions, such as MetS, diabetes, and hypertension. In this study we examined the association of low-level lead exposure (measured in bone) with alterations in HRV among community residents with no previously known heavy lead exposure. We also assessed effect modifications by MetS and its individual components.