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      Lead Exposure and Cardiovascular Disease—A Systematic Review


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          This systematic review evaluates the evidence on the association between lead exposure and cardiovascular end points in human populations.


          We reviewed all observational studies from database searches and citations regarding lead and cardiovascular end points.


          A positive association of lead exposure with blood pressure has been identified in numerous studies in different settings, including prospective studies and in relatively homogeneous socioeconomic status groups. Several studies have identified a dose–response relationship. Although the magnitude of this association is modest, it may be underestimated by measurement error. The hypertensive effects of lead have been confirmed in experimental models. Beyond hypertension, studies in general populations have identified a positive association of lead exposure with clinical cardiovascular outcomes (cardiovascular, coronary heart disease, and stroke mortality; and peripheral arterial disease), but the number of studies is small. In some studies these associations were observed at blood lead levels < 5 μg/dL.


          We conclude that the evidence is sufficient to infer a causal relationship of lead exposure with hypertension. We conclude that the evidence is suggestive but not sufficient to infer a causal relationship of lead exposure with clinical cardiovascular outcomes. There is also suggestive but insufficient evidence to infer a causal relationship of lead exposure with heart rate variability.

          Public Health Implications

          These findings have immediate public health implications. Current occupational safety standards for blood lead must be lowered and a criterion for screening elevated lead exposure needs to be established in adults. Risk assessment and economic analyses of lead exposure impact must include the cardiovascular effects of lead. Finally, regulatory and public health interventions must be developed and implemented to further prevent and reduce lead exposure.

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          Most cited references109

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          Impact of Reduced Heart Rate Variability on Risk for Cardiac Events: The Framingham Heart Study

          Although heart rate variability (HRV) is altered in a variety of pathological conditions, the association of reduced HRV with risk for new cardiac events has not been studied in a large community-based population. The first 2 hours of ambulatory ECG recordings obtained on subjects of the Framingham Heart Study who were free of clinically apparent coronary heart disease or congestive heart failure were reprocessed to assess HRV. Five frequency-domain measures and three time-domain measures were obtained. The associations between HRV measures and the incidence of new cardiac events (angina pectroris, myocardial infarction, coronary heart disease death, or congestive heart failure) were assessed with proportional hazards regression analyses. There were 2501 eligible subjects with a mean age of 53 years. During a mean follow-up of 3.5 years, cardiac events occurred in 58 subjects. After adjustment for age, sex, cigarette smoking, diabetes, left ventricular hypertrophy, and other relevant risk factors, all HRV measures except the ratio of low-frequency to high-frequency power were significantly associated with risk for a cardiac event (P = .0016 to .0496). A one-standard deviation decrement in the standard deviation of total normal RR intervals (natural log transformed) was associated with a hazard ratio of 1.47 for new cardiac events (95% confidence interval of 1.16 to 1.86). The estimation of HRV by ambulatory monitoring offers prognostic information beyond that provided by the evaluation of traditional cardiovascular disease risk factors.
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            Blood lead below 0.48 micromol/L (10 microg/dL) and mortality among US adults.

            Blood lead levels above 0.48 micromol/L (10 microg/dL) in adults have been associated with increased risk of cardiovascular, cancer, and all-cause mortality. The objective of the present study was to determine the association between blood lead levels below 0.48 micromol/L and mortality in the general US population. Blood lead levels were measured in a nationally representative sample of 13,946 adult participants of the Third National Health and Nutrition Examination Survey recruited in 1988 to 1994 and followed up for up to 12 years for all-cause and cause-specific mortality. The geometric mean blood lead level in study participants was 0.12 micromol/L (2.58 microg/dL). After multivariate adjustment, the hazard ratios (95% CI) for comparisons of participants in the highest tertile of blood lead (> or = 0.17 micromol/L [> or = 3.62 microg/dL]) with those in the lowest tertile ( 0.10 micromol/L (> or = 2 microg/dL). There was no association between blood lead and cancer mortality in this range of exposure. The association between blood lead levels and increased all-cause and cardiovascular mortality was observed at substantially lower blood lead levels than previously reported. Despite the marked decrease in blood lead levels over the past 3 decades, environmental lead exposures remain a significant determinant of cardiovascular mortality in the general population, constituting a major public health problem.
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              Lead, cadmium, smoking, and increased risk of peripheral arterial disease.

              Lead and cadmium exposure may promote atherosclerosis, although the cardiovascular effects of chronic low-dose exposure are largely unknown. The objective of the present study was to evaluate the association between blood levels of lead and cadmium and peripheral arterial disease. We analyzed data from 2125 participants who were > or =40 years of age in the 1999 to 2000 National Health and Nutrition Examination Survey (NHANES). Peripheral arterial disease was defined as an ankle brachial index <0.9 in at least 1 leg. Lead and cadmium levels were measured by atomic absorption spectrometry. After adjustment for demographic and cardiovascular risk factors, the ORs of peripheral arterial disease comparing quartiles 2 to 4 of lead with the lowest quartile were 1.63 (95% CI, 0.51 to 5.15), 1.92 (95% CI, 0.62 to 9.47), and 2.88 (95% CI, 0.87 to 9.47), respectively (P for trend=0.02). The corresponding ORs for cadmium were 1.07 (95% CI, 0.44 to 2.60), 1.30 (95% CI, 0.69 to 2.44), and 2.82 (95% CI, 1.36 to 5.85), respectively (P for trend=0.01). The OR of peripheral arterial disease for current smokers compared with never smokers was 4.13. Adjustment for lead reduced this OR to 3.38, and adjustment for cadmium reduced it to 1.84. Blood lead and cadmium, at levels well below current safety standards, were associated with an increased prevalence of peripheral arterial disease in the general US population. Cadmium may partially mediate the effect of smoking on peripheral arterial disease.

                Author and article information

                Environ Health Perspect
                Environmental Health Perspectives
                National Institute of Environmental Health Sciences
                March 2007
                22 December 2006
                : 115
                : 3
                : 472-482
                [1 ] Department of Environmental Health Sciences and
                [2 ] Departments of Epidemiology and Medicine, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
                [3 ] Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, Maryland, USA
                [4 ] Centro de Investigación y de Estudios Avanzados – Instituto Politécnico Nacional (CINVESTAV-IPN), Mérida, Yucatán, México
                [5 ] Instituto Nacional de Salud Pública, Cuernavaca, Morelos, México
                Author notes
                Address correspondence to S. Rothenberg, Departamento, Ecología Humana, Centro de Investigación y de Estudios Avanzados—Instituto Politécnico Nacional (CINVESTAV-IPN), Carretera Antigua a Progreso km 6, 97310 Mérida, Yucatán, México. Telephone: 52 999 124 2109. Fax: 52 739 395 0662. E-mail: srothenberg@ 123456mda.cinvestav.mx

                The authors declare they have no competing financial interests.

                A.N-A. was supported by grant P30 ES 03819 from the National Institute of Environmental Health Sciences Center in Urban Environmental Health.

                This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI
                : 3 October 2006
                : 20 December 2006

                Public health
                systematic review,heart rate variability,hypertension,cardiovascular disease,lead,blood pressure,atherosclerosis


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