Abstract
BACKGROUND
Lead contamination can affect many body organs including the heart. This study assessed a number of echocardiographic indices to clarify the effects of lead on cardiac function among battery factory workers who are in constant exposure to lead.
METHODS
In a cross-sectional study, 142 male battery factory workers who had been exposed to lead for at least 1 year were evaluated. The subjects aged 25-55 years old and were excluded if they had hypertension, diabetes, or cardiovascular diseases. Demographic characteristics, professional profile, lead exposure, history of respiratory diseases, drugs intake, and lifestyle information of the participants were collected. Height, weight and blood pressure measurements were then performed. Blood tests were also ordered to determine blood lead levels. The subjects finally underwent M-mode and Doppler echocardiography. Linear regression analysis was used to establish the effects of lead on the target indices. All statistical analyses were conducted in SPSS18.
RESULTS
The mean age and mean duration of lead exposure of the subjects were 41.78 ± 13.58 and 23.54 ± 14.44 years, respectively. The mean blood lead level was 7.59 ± 2.75 µg/dl. Left ventricular hypertrophy was detected in 12% of the participants. Blood lead levels were not significantly related with echocardiographic indices in the crude model or after adjustments for age alone or for age and other risk factors.
CONCLUSION
Blood lead levels of our participants were below standard values. In addition, no significant relation was found between left ventricular function indices and blood lead levels. The absence of such relations could have been caused by the exclusion of individuals with hypertension or cardiovascular diseases. Structural modifications in battery factories following legislations in Iran might have been responsible for low blood lead levels among the subjects.
Keywords: Occupational Exposure, Lead, Left Ventricular Echocardiography
Introduction
Lead contamination involves a wide variety of body organs.1 Long exposure to lead may result in memory impairment, increased reaction time, and inability to perceive information. It may also cause physical complications such as hypertension, renal complications, cognitive and psychiatric disorders, hemoglobin disorders and anemia, peripheral vascular disease,2 and cancers including lung and stomach cancers and glioma.3
Among the numerous lead-containing products, leaded gasoline and batteries are the most important.4 The extent of complications depends on exposure dose and duration, age, occupation, general health, and lifestyle.5 However, even small occupational exposure doses would cause impaired cardiac function.6 In addition, even little increases in blood lead level are associated with peripheral vascular disease7 and hypertension.8 Various blood levels of lead have been suggested as the risk factor for cardiovascular diseases and mortality in different societies. While cohort studies on individuals at occupational exposure to lead have reported a level above 40 µg/dl to be a risk factor for the mentioned problems, community-level studies found lead blood levels of higher than 10 µg/dl to be correlated with atherosclerosis, cardiovascular diseases, and increased mortality.9-11
Despite the absence of a well-established mechanism through which lead affects the heart, two main mechanisms have been suggested. Some researchers have identified lead to increase blood pressure and hence negatively affect the heart and coronary arteries. Others however, have considered increased atherosclerosis caused by lead to be responsible.12 Lead has also been indicated as an independent risk factor for the incidence of cardiovascular diseases.13
Left ventricular function is among the most important indices in determining the prognosis of heart diseases. Various methods are available to qualitatively and quantitatively assess left ventricular function. Echocardiography is a non-invasive method which not only evaluates left ventricular function, but also determines the reason for the impaired ventricular function.14 The present research tried to assess echocardiographic indices among battery factory workers to clarify the effects of lead on cardiac function.
Materials and Methods
In a cross-sectional study during 2011, 142 male battery factory workers in Isfahan (Iran) were selected using convenience sampling. The subjects aged 25-55 years old and had been chronically exposed to lead for at least one year. Individuals with a history of diabetes, hypertension, heart or kidney diseases, and cancers, as well as those using drugs affecting blood pressure were excluded.
After explaining the objectives of the study, informed consents were obtained. A questionnaire covering demographics (age, gender, education level, and marital status), job-related information, history of lead exposure (job, working experience, previous jobs, and how they were exposed), respiratory disease history, medicine intake, and lifestyle (smoking, leisure time physical activity, and diet) was then completed for all subjects.
The next step was to measure height (using a Seca measuring band) and weight (using a Seca scale) and to calculate body mass index (BMI) as weight divided by height squared. In addition, 3 measurements of sitting blood pressure with 5-minute intervals were performed after 20 minutes of rest. The 3 values were averaged and recorded as each person's blood pressure.
Venous blood samples were taken from all subjects in the early morning and kept in lead-free heparinized tubes at 4°C. Blood lead levels were then evaluated by a flameless atomic absorption spectrophotometer.8
After completing the questionnaires and performing the necessary examinations and tests, M-mode and Doppler echocardiography were performed on all subjects by a cardiologist and according to the guidelines of American Society of Echocardiography.15 Left ventricular end-diastolic dimension (LVEDd), interventricular septum (IVS), posterior wall thickness (PWT), left atrium diameter (LAD), aortic diameter (AoD), left ventricular ejection fraction (LVEF), left ventricular mass (LVM), left ventricular mass index (LVMI), and early to late diastolic filling (E/A) were measured in the echocardiogram. All measurements were made by a Vivid-3 Cardiology Ultrasound Machine and an adult probe. In M-mode echocardiography, parasternal long axis view and parasternal short axis view at the level of papillary muscle were used to determine left ventricular dimensions. In the absence of any regional wall motion abnormalities, measurements were made at mid-ventricular level. PWT and IVS were also measured on the same section. The obtained data was used to calculate LVM and LVMI.16 According to Penn's formula, an LVM level higher than 177 g was identified as left ventricular hypertrophy.17
Maximum and minimum ventricular sizes at mitral valve level were considered as end-systolic and end-diastolic dimensions, respectively.15 LVEF was determined based on Simpson method. Doppler echocardiography was employed to determine E/A. Mitral blood flow velocity was measured in the apical view at end-expiration and maximum flow.18
The collected data was analyzed in SPSS18 (SPSS Inc., Chicago, IL, USA). The relations between blood lead levels and cardiac function indices were assessed by correlations. Using a linear regression model, first the crude effects of lead on the mentioned indices were determined. The model was then adjusted for smoking, daily physical activity, systolic blood pressure, BMI, and age to reevaluate the effects.
Results
A total number of 142 male battery factory workers with a mean age of 41.78 ± 13.58 years (range: 21.00-72.00 years) were evaluated. Demographic characteristics of the subjects are summarized in table 1. More than 50% of the participants were illiterate or had completed elementary school. They had been working in battery making profession for 23.54 ± 14.44 years. Moreover, their daily working hours were 9.77 ± 2.26 (range: 5.00-16.00 hours) and 62% of the subjects worked more than 8 hours a day. Most workers (79.7%) were exposed to lead through both inhalation and skin. The mean blood lead level among the participants was 7.59 ± 2.75 µg/dl (range: 2.60-16.10 µg/dl).
Table 1.
Variables | Value |
---|---|
Age (years) | 41.78 ± 13.58 |
Educational level | |
Illiterate | 3 (2.1%) |
Junior high school | 69 (48.3%) |
High school | 50 (35.0%) |
University degree | 20 (14.0%) |
Marital Status(married) | 118 (82.5%) |
Average monthly payment(Toman) | |
Less than 300,000 | 36 (25.2%) |
300,000-500,000 | 105 (73.4%) |
500,000-800,000 | 1 (0.7%) |
Values are expressed as mean ± SD or number (%).
Table 2 presents the history of diseases and lifestyle-related factors. Echocardiography findings among the studied population are shown in table 3. LVM ranged from 62.67 to 248.48 g and 12% of the subjects had left ventricular hypertrophy. The mean blood lead levels were not significantly different between individuals with LVM higher than 177 g and others (8.05 ± 2.84 vs. 7.55 ± 2.75 µg/dL; P = 0.501).
Table 2.
Variables | Values |
---|---|
History of dyslipidemia | 16 (11.2%) |
History of respiratory diseases | 18 (12.6%) |
Regular physical activity * | 57 (39.9%) |
days/ week | 3.50 ± 2.57 |
minute/day | 16.48 ± 27.07 |
Smoking | |
Non-smoker | 97 (67.8%) |
Ex-smoker | 19 (13.3%) |
Smoker | 26 (18.2%) |
Bodymass index (kg/m 2 ) | 25.70 ± 3.72 |
Systolic blood pressure (mmHg) | 111.52 ±13.60 |
Diastolic blood pressure (mmHg) | 70.06 ± 8.95 |
Values are expressed as mean ± SD or number (%).
Table 3.
Variable | Mean ± SD |
---|---|
Left ventricular end-diastolicdimension (mm) | 47.6 ± 5.3 |
Interventricular septal (mm) | 8.50 ± 3.20 |
Posterior wall thickness (mm) | 8.30 ± 1.20 |
Left atrium diameter(mm) | 35.60 ± 3.80 |
Aortic diameter (mm) | 28.80 ± 5.30 |
Left ventricular ejection fraction (%) | 62.49 ± 4.51 |
Left ventricular mass (g) | 133.91 ± 34.18 |
Left ventricular mass index | 76.29 ± 58.71 |
Early to late diastolic filling | 1.83 ± 2.45 |
Table 4 reports the effects of lead on echocardiographic indices in the crude model and two models adjusted for age, and for age, disease history, physical activity, smoking, and BMI. As it is seen, blood lead levels had no significant effects on any of the echocardiographic indices in either the crude model, or the adjusted models.
Table 4.
Beta | P | 95% confidence interval | |
---|---|---|---|
Crude model: | |||
Leftventricular end-diastolicdimension | -0.029 | 0.733 | (-0.039-0.027) |
Interventricular septal | -0.045 | 0.600 | (-0.025-0.015) |
Posterior wallthickness | 0.057 | 0.505 | (-0.005-0.010) |
Left atriumdiameter | -0.010 | 0.905 | (-0.025-0.022) |
Aortic diameter | -0.013 | 0.879 | (-0.031-0.036) |
Leftventricular ejection fraction | 0.013 | 0.877 | (-0.257-0.301) |
Leftventricular mass | 0.003 | 0.975 | (-2.067-2.132) |
Leftventricular mass index | -0.119 | 0.167 | (-6.218-1.0684) |
Early to late diastolic filling | -0.019 | 0.825 | (-0.170-136) |
Second model:* | |||
Leftventricular end-diastolicdimension | -0.031 | 0.721 | -0.039-0.027 |
Interventricular septal | -0.048 | 0.575 | -0.026-0.014 |
Posterior wallthickness | 0.050 | 0.552 | -0.005-0.010 |
Left atriumdiameter | -0.015 | 0.862 | -0.026-0.022 |
Aortic diameter | 0.012 | 0.890 | -0.031-0.036 |
Leftventricular ejection fraction | 0.016 | 0.857 | -0.254-0.303 |
Leftventricular mass | -0.004 | 0.961 | -2.123-2.021 |
Leftventricular mass index | -0.118 | 0.170 | -6.232-1.114 |
Early to late diastolic filling | -0.015 | 0.857 | -0.167-0.139 |
Third model:** | |||
Leftventricular end-diastolicdimension | -0.005 | 0.954 | -0.035-0.033 |
Interventricular septal | -0.040 | 0.656 | -0.026-0.016 |
Posterior wallthickness | 0.081 | 0.334 | -0.004-0.011 |
Left atriumdiameter | 0.020 | 0.815 | -0.021-0.027 |
Aortic diameter | 0.001 | 0.992 | -0.035-0.35 |
Leftventricular ejection fraction | 0.041 | 0.651 | -0.222-0.354 |
Leftventricular mass | 0.042 | 0.611 | -1.437-2.435 |
leftventricular mass index | 0.029 | 0.746 | -1.074-1.495 |
Early to late diastolic filling | -0.018 | 0.840 | -0.179-0.146 |
Adjusted for age
Adjusted for age, body mass index, smoking, physical activity, and systolic and diastolic blood pressure
Discussion
The present study revealed mean blood lead levels of 142 male battery factory workers to be below the standard level. In addition, lead levels were not found to be associated with any of left ventricular function indices.
A number of other studies have also evaluated the effects of lead on left ventricular function indices. Tepper et al. assessed the relation between lead levels and measured blood pressure in 108 battery factory workers. They reported blood lead levels to be significantly associated with diastolic blood pressure, but non-significantly related with systolic blood pressure and LVM.19 Similarly, we found lead to non-significantly and slightly affect left ventricular function indices.
Zou et al. suggested E/A to be significantly lower in lead-exposed subjects compared to unexposed individuals.20 Schwartz studied 9932 American adults whose information was collected by the Second National Health and Nutrition Examination Survey. Finally, blood lead level was reported to significantly, but not strongly, affect left ventricular hypertrophy
(P = 0.0087; B = 0.028).21 We however, could not establish a significant relation between blood lead levels and LVM. The difference between the two studies might have been resulted by the greater number of evaluated persons by Schwartz.
In another study, Kasperczyk et al. compared a group of lead-exposed individuals with a control group working in lead factories in Southern Poland.
IVS, LVDd, PW, LVEF, LAD, AoD, and right ventricular diastolic dimension were evaluated through echocardiography. While LVEF was 3% less in lead-exposed individuals compared to the control group, LVDd and LVM were respectively 6% and 11% higher. Blood lead level was found to have significant positive relations with LVDd and LVM.22 Since blood pressure has an independent effect on left ventricular hypertrophy and function,23-25 we excluded hypertensive or cardiovascular patients. However, Kasperczyk et al. did not eliminate the confounding factor of blood pressure.22
A review article suggested that despite the observed cardiovascular effects of lead, adequate evidence to confirm the relationship has not yet been provided.26 Another review article evaluated studies on the effects of chronic lead exposure on cardiovascular function and diseases. It suggested that although animal, tissue, and cell cultivation models had found lead to be effective on blood pressure, endothelial injury and dysfunction, atherosclerosis, and cardiovascular diseases, evidence is still insufficient to validate such a mechanism at clinical and epidemiological levels.27
As mentioned, previous studies could not establish the definite effects of lead on left ventricular function and echocardiographic indices. However, some research has revealed lead to affect cardiovascular diseases and their associated mortality.2,28 Stimulation of the oxidative stress system, inflammation, alteration of nitric oxide signaling pathways, endothelial injury, vascular smooth muscle cells proliferation, and inhibition of fibrinolysis have been suggested as the probable mechanisms through which lead impacts on cardiac function.29
Conclusion
The present study could not indicate a significant relation between blood lead levels and echocardiographic indices of left ventricular function. Eliminating hypertensive and cardiovascular patients, as the high risk population, might have been responsible for the lack of relation. On the other hand, the low blood lead levels may suggest structural improvements in battery factories after introducing new legislations in Iran. Evaluating other factors such as bone lead level, which is a better indicator of chronic lead-exposure, may result in different findings. Moreover, longitudinal studies on the incidence and mortality of cardiovascular diseases among lead-exposed individuals can provide more useful information.
Footnotes
Conflicts of Interest
Authors have no conflict of interests.
REFERENCES
- 1.Jarup L. Hazards of heavy metal contamination. Br Med Bull. 2003;68:167–82. doi: 10.1093/bmb/ldg032. [DOI] [PubMed] [Google Scholar]
- 2.Schober SE, Mirel LB, Graubard BI, Brody DJ, Flegal KM. Blood lead levels and death from all causes, cardiovascular disease, and cancer: results from the NHANES III mortality study. Environ Health Perspect. 2006;114(10):1538–41. doi: 10.1289/ehp.9123. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Steenland K, Boffetta P. Lead and cancer in humans: where are we now? Am J Ind Med. 2000;38(3):295–9. doi: 10.1002/1097-0274(200009)38:3<295::aid-ajim8>3.0.co;2-l. [DOI] [PubMed] [Google Scholar]
- 4.Agency for Toxic Substances and Disease Registry. 2007. Available from: http://www.atsdr.cdc.gov/toxprofiles/tp.asp?id=96&tid=22/
- 5.Sanders T, Liu Y, Buchner V, Tchounwou PB. Neurotoxic effects and biomarkers of lead exposure: a review. Rev Environ Health. 2009;24(1):15–45. doi: 10.1515/reveh.2009.24.1.15. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Glenn BS, Stewart WF, Links JM, Todd AC, Schwartz BS. The longitudinal association of lead with blood pressure. Epidemiology. 2003;14(1):30–6. doi: 10.1097/00001648-200301000-00011. [DOI] [PubMed] [Google Scholar]
- 7.Aiba Y, Ohshiba S, Horiguchi S, Morioka I, Miyashita K, Kiyota I, et al. Peripheral hemodynamics evaluated by acceleration plethysmography in workers exposed to lead. Ind Health. 1999;37(1):3–8. doi: 10.2486/indhealth.37.3. [DOI] [PubMed] [Google Scholar]
- 8.Fenga C, Cacciola A, Martino LB, Calderaro SR, Di NC, Verzera A, et al. Relationship of blood lead levels to blood pressure in exhaust battery storage workers. Ind Health. 2006;44(2):304–9. doi: 10.2486/indhealth.44.304. [DOI] [PubMed] [Google Scholar]
- 9.Menke A, Muntner P, Batuman V, Silbergeld EK, Guallar E. Blood lead below 0.48 micromol/L (10 microg/dL) and mortality among US adults. Circulation. 2006;114(13):1388–94. doi: 10.1161/CIRCULATIONAHA.106.628321. [DOI] [PubMed] [Google Scholar]
- 10.Navas-Acien A, Selvin E, Sharrett AR, Calderon-Aranda E, Silbergeld E, Guallar E. Lead, cadmium, smoking, and increased risk of peripheral arterial disease. Circulation. 2004;109(25):3196–201. doi: 10.1161/01.CIR.0000130848.18636.B2. [DOI] [PubMed] [Google Scholar]
- 11.Lustberg M, Silbergeld E. Blood lead levels and mortality. Arch Intern Med. 2002;162(21):2443–9. doi: 10.1001/archinte.162.21.2443. [DOI] [PubMed] [Google Scholar]
- 12.Jain NB, Potula V, Schwartz J, Vokonas PS, Sparrow D, Wright RO, et al. Lead levels and ischemic heart disease in a prospective study of middle-aged and elderly men: the VA Normative Aging Study. Environ Health Perspect. 2007;115(6):871–5. doi: 10.1289/ehp.9629. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Kaewboonchoo O, Morioka I, Saleekul S, Miyai N, Chaikittiporn C, Kawai T. Blood lead level and cardiovascular risk factors among bus drivers in Bangkok, Thailand. Ind Health. 2010;48(1):61–5. doi: 10.2486/indhealth.48.61. [DOI] [PubMed] [Google Scholar]
- 14.Pinto FJ. Echocardiography in left ventricular dysfunction. Ital Heart J. 2004;5 (Suppl 6):41S. [PubMed] [Google Scholar]
- 15.Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr. 2005;18(12):1440–63. doi: 10.1016/j.echo.2005.10.005. [DOI] [PubMed] [Google Scholar]
- 16.Levy D, Savage DD, Garrison RJ, Anderson KM, Kannel WB, Castelli WP. Echocardiographic criteria for left ventricular hypertrophy: the Framingham Heart Study. Am J Cardiol. 1987;59(9):956–60. doi: 10.1016/0002-9149(87)91133-7. [DOI] [PubMed] [Google Scholar]
- 17.Foppa M, Duncan BB, Rohde LE. Echocardiography-based left ventricular mass estimation. How should we define hypertrophy? Cardiovasc Ultrasound. 2005;3:17. doi: 10.1186/1476-7120-3-17. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.Poerner TC, Goebel B, Kralev S, Kaden JJ, Suselbeck T, Haase KK, et al. Impact of mitral E/A ratio on the accuracy of different echocardiographic indices to estimate left ventricular end-diastolic pressure. Ultrasound Med Biol. 2007;33(5):699–707. doi: 10.1016/j.ultrasmedbio.2006.11.014. [DOI] [PubMed] [Google Scholar]
- 19.Tepper A, Mueller C, Singal M, Sagar K. Blood pressure, left ventricular mass, and lead exposure in battery manufacturing workers. Am J Ind Med. 2001;40(1):63–72. doi: 10.1002/ajim.1072. [DOI] [PubMed] [Google Scholar]
- 20.Zou HJ, Ding Y, Huang KL, Xu ML, Tang GF, Wu MH, et al. Effects of lead on systolic and diastolic cardiac functions. Biomed Environ Sci. 1995;8(4):281–8. [PubMed] [Google Scholar]
- 21.Schwartz J. Lead, blood pressure, and cardiovascular disease in men and women. Environ Health Perspect. 1991;91:71–5. doi: 10.1289/ehp.919171. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Kasperczyk S, Przywara-Chowaniec B, Kasperczyk A, Rykaczewska-Czerwinska M, Wodniecki J, Birkner E, et al. Function of heart muscle in people chronically exposed to lead. Ann Agric Environ Med. 2005;12(2):207–10. [PubMed] [Google Scholar]
- 23.Katholi RE, Couri DM. Left ventricular hypertrophy: major risk factor in patients with hypertension: update and practical clinical applications. Int J Hypertens. 2011;2011:495349. doi: 10.4061/2011/495349. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Schafer S, Kelm M, Mingers S, Strauer BE. Left ventricular remodeling impairs coronary flow reserve in hypertensive patients. J Hypertens. 2002;20(7):1431–7. doi: 10.1097/00004872-200207000-00031. [DOI] [PubMed] [Google Scholar]
- 25.Cuspidi C, Negri F, Sala C, Mancia G. Masked hypertension and echocardiographic left ventricular hypertrophy: an updated overview. Blood Press Monit. 2012;17(1):8–13. doi: 10.1097/MBP.0b013e32834f713a. [DOI] [PubMed] [Google Scholar]
- 26.Navas-Acien A, Guallar E, Silbergeld EK, Rothenberg SJ. Lead exposure and cardiovascular disease-a systematic review. Environ Health Perspect. 2007;115(3):472–82. doi: 10.1289/ehp.9785. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Vaziri ND. Mechanisms of lead-induced hypertension and cardiovascular disease. Am J Physiol Heart Circ Physiol. 2008;295(2):H454–H465. doi: 10.1152/ajpheart.00158.2008. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Peters JL, Kubzansky LD, Ikeda A, Fang SC, Sparrow D, Weisskopf MG, et al. Lead concentrations in relation to multiple biomarkers of cardiovascular disease: the Normative Aging Study. Environ Health Perspect. 2012;120(3):361–6. doi: 10.1289/ehp.1103467. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Vaziri ND, Gonick HC. Cardiovascular effects of lead exposure. Indian J Med Res. 2008;128(4):426–35. [PubMed] [Google Scholar]