Cumulative Community-Level Lead Exposure and Pulse Pressure: The Normative Aging Study

Todd Perlstein; Jennifer Weuve; Joel Schwartz; David Sparrow; Robert Wright; Augusto Litonjua; Huiling Nie; Howard Hu


Environ Health Perspect. 2007;115(12):1696-1700. 

In This Article

Abstract and Introduction


Background: Pulse pressure increases with age in industrialized societies as a manifestation of arterial stiffening. Lead accumulates in the vasculature and is associated with vascular oxidative stress, which can promote functional and structural vascular disease.
Objectives: We tested the hypothesis that cumulative community-level lead exposure, measured with K-X-ray fluorescence, is associated with pulse pressure in a cohort of adult men.
Methods and results: In a cross-sectional analysis of 593 men not treated with antihypertensive medication, tibia lead was positively associated with pulse pressure (p<0.001). Adjusting for age, race, diabetes, family history of hypertension, education, waist circumference, alcohol intake, smoking history, height, heart rate, fasting glucose, and total cholesterol-to-HDL ratio, increasing quintiles of tibia lead remained associated with increased pulse pressure (p trend= 0.02) . Men with tibia lead above the median (19.0 μg/g) had, on average, a 4.2-mmHg (95% confidence interval, 1.9-6.5) higher pulse pressure than men with tibia lead level below the median. In contrast, blood lead level was not associated with pulse pressure.
Conclusions: These data indicate that lead exposure may contribute to the observed increase in pulse pressure that occurs with aging in industrialized societies. Lead accumulation may contribute to arterial aging, perhaps providing mechanistic insight into the observed association of low-level lead exposure with cardiovascular mortality.


In industrialized societies, pulse pressure (systolic minus diastolic blood pressure) increases with age, a trend that accelerates in the sixth decade when the diastolic blood pressure begins to decrease (Franklin et al. 1997). The increase in pulse pressure reflects arterial aging and progressive vascular stiffening (Lakatta and Levy 2003), with the predominant contribution from increased aortic stiffness (Mitchell et al. 2004). Vascular oxidative stress contributes to arterial aging (Lakatta 2003). Accordingly, known contributors to vascular oxidative stress including obesity (Kwagyan et al. 2005), smoking (Mahmud and Feely 2003), hyperglycemia (van Dijk et al. 2002), and dyslipidemia (Miyagi et al. 2002) are associated with increased pulse pressure.

Lead exposure is also associated with vascular oxidative stress (Vaziri 2002). In vivo (Vaziri et al. 1999) and in vitro (Vaziri and Ding 2001) studies of lead demonstrate increased vascular reactive oxygen species generation. Lead accumulates in the vasculature of the lead-exposed rat and remains after the exposure has ended (Malvezzi et al. 2001). The lead-exposed rat develops hypertension ameliorable by antioxidant therapy (Vaziri et al. 1997). These findings suggest that accumulation of lead in the arterial tree may contribute to arterial stiffness by inducing oxidative stress.

In industrialized societies, accumulation of bone lead is many times greater than that observed in cultures that do not use lead (Drasch 1982). Therefore, bone lead may serve as a proxy marker of lead accumulated in the arterial tree. In fact, human autopsy studies demonstrate age- and dose-dependent aortic lead deposition and suggest that the aorta is the next most lead-avid tissue after bone (Barry and Mossman 1970; Schroeder and Tipton 1968). Although public health initiatives have been successful at lessening environmental lead exposures in the United States (Muntner et al. 2005), low-level lead exposure remains an important contributor to all-cause and cardiovascular mortality (Menke et al. 2006).

The effect of low-level environmental exposure to lead on blood pressure is an area of ongoing scientific debate. Some investigators have found the relationship between low-level lead exposure and blood pressure to be inconsistent and weak (Nawrot et al. 2002; Staessen et al. 1994), but several toxicologic studies by have found that lead elevates blood pressure (Khalil-Manesh et al. 1993; Vaziri et al. 1997; Victery et al. 1982). Other investigators have noted the consistency of the effect size of the blood lead-blood pressure association, and its significance in meta-analyses (Navas-Acien et al. 2007; Schwartz 1991, 1995). A limitation of this body of work is the use of lead in blood as a metric of exposure, where the median residence time of lead is measured in days. Yet autopsy studies indicate that around 95% of lead in the adult human body is deposited in the skeleton, and to the extent that the lead's effect on blood pressure can be attributed to chronic exposures, a longer averaging time for exposure would be more relevant for evaluating these effects. For example, using K-X-ray fluorescence (KXRF) to directly measure levels of lead retained in bone, we have found that bone lead, compared with blood lead, more accurately reflects cumulative lead exposure (Hu et al. 1996b). We have also found bone lead level to be more strongly associated than blood lead level with blood pressure and hypertension in adult men (Cheng et al. 2001; Hu et al. 1996a).

We examined the cross-sectional association of community-level lead exposure with pulse pressure in the Normative Aging Study, a longitudinal cohort of men. We analyzed this association using both bone and blood lead levels, anticipating that the former, a more accurate indicator of cumulative lead exposure, would be more strongly associated with pulse pressure.


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