Lead Exposure Is Related to Impairment of Aortic Elasticity Parameters

Abstract

Arterial hypertension is one of the physical complications of chronic lead exposure. Hypertension has effects on aortic elastic properties. The aim of this study was to evaluate the aortic elastic properties in workers occupationally exposed to lead. Forty‐one workers who were exposed to lead and 39 healthy controls were included in the study. All patients underwent transthoracic echocardiography for detecting aortic elastic parameters. There were no differences in baseline characteristics between the lead‐exposure group and controls. Aortic strain (9.4%±4.5% vs 12.4%±4.2%, P=.004) and aortic distensibility (0.45±0.21 cm²/dyn vs 0.55±0.20 cm²/dyn, P=.046) were decreased in patients with lead exposure compared with controls. There was a negative significant weak correlation between aortic strain and (r=−0.294, P=.008) lead levels. There was no significant correlation between aortic distensibility and any other echocardiographic parameters. This study suggests that chronic exposure to lead is related to impairment of aortic elasticity parameters.

Lead contamination (such as that emitted from house paint, gasoline, batteries, and other sources) may cause a wide variety of body organ complications.1 Despite the still manifested divergences of opinion, it seems that chronic exposure to lead represents a risk for arterial hypertension development. Functional changes within the arterial wall both in smooth muscles and the endothelium might result in arterial hypertension caused by chronic exposure to lead compounds.2

Blood pressure (BP) was found to be increased in workers with blood lead concentrations of 7 μg/L on average.3 According to the World Health Organization (2000), the level of 400 μg/L is accepted as safe to avoid possible adverse health effects, but American Conference Governmental and Industrial Hygienists suggest an even lower value of <300 μg/L.

Hypertension has effects on the aorta (decreased aortic distensibility and increased aortic stiffness). Aortic strain is a simple and useful parameter of transthoracic echocardiography. Some studies have suggested that aortic elastic parameters can be used as an independent predictor of all‐cause and cardiovascular mortality in hypertensive patients.4, 5

In previous studies, the relationship between lead exposure and arterial hypertension has been demonstrated, and findings suggest that arterial hypertension and organ complications of arterial hypertension are more frequent in workers with lead exposure. Until now, there have been no data on the effects of lead exposure on aortic stiffness. The aim of this study was to evaluate the effects of lead on aortic elasticity parameters.

Methods

Patients

We examined 41 consecutive industrial male employees occupationally exposed to lead who were admitted to the Occupational Disease Hospital for high lead concentrations and 39 normotensive healthy controls. All patients were normotensive. Healthy controls were individuals with no known overt disease and normal systolic and diastolic BP. All patients underwent transthoracic echocardiography after a complete medical history and laboratory examination. Patients' height, weight, and BP on the day of echocardiography were recorded.

Patients with hypertension, diabetes mellitus, coronary heart disease, systolic heart failure, and acute or chronic renal failure were excluded. The study protocol was in accordance with the Declaration of Helsinki and was approved by the local ethics committee. All patients provided informed consent before enrollment.

BP Measurement

The BP of each patient was measured from the left arm twice by one of the clinicians of the research team following approximately 5 minutes of seated rest. Participants were advised to avoid alcohol, cigarettes, coffee/tea, and exercise for at least 30 minutes before BP measurement. Standardized mercury sphygmomanometers were used, and one of two cuff sizes was chosen on the basis of the circumference of the participant's arm. Korotkoff phase I (appearance) and phase V (disappearance) sounds were recorded for systolic BP (SBP) and diastolic BP (DBP), respectively. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) criteria were used for defining hypertension.6

Transthoracic Echocardiography

All echocardiographic examinations were performed with the ESAOTE cardiac ultrasound scanner (Indianapolis, IN) and 2.5‐MHz to 3.5‐MHz transducers. All patients were examined in the left lateral position by precordial M‐mode, 2‐dimensional, and Doppler echocardiography.

Left ventricular (LV) end‐diastolic and end‐systolic diameters, ejection fraction, end‐systolic left atrial diameters, and aortic root diameters were measured from M mode in the parasternal long‐axis views.

Doppler Echocardiography

Flow velocity indexes were obtained using pulsed and continuous wave Doppler from apical projections, and measurements were made using the software of the ultrasound equipment. Mitral diastolic flow was obtained after the pulsed Doppler sample volume was positioned perpendicular to the tips of the mitral valve leaflets. The following indexes were measured from the mitral valve diastolic wave form: peak early (E) and atrial (A) flow velocities (m/s), E/A ratio, deceleration time (DT) (ms), and isovolumetric relexation time (IVRT) of the LV diastolic filling.

Calculation of Aortic Root Strain and Distensibility

Aortic systolic diameter (AoS) was measured at the time of full opening of the aortic valve and diastolic diameter (AoD) at the R wave of the superimposed electrocardiogram by 2‐dimensional–guided M‐mode echocardiography 3 cm above the aortic valve in parasternal long‐axis view. BP was measured by arm sphygmomanometry. Two indices of aortic root elastic properties were calculated blindly: (1) aortic strain (%) = (AoS−AoD) × 100/AoD, (2) distensibility (D) = (2 × aortic strain)/pulse pressure.2, 7

Blood Samples and Analysis

Venous blood samples were collected from lead‐exposed workers and from the control group after a 12‐hour fasting period into tubes containing clot activator (to obtain serum). Collected samples were sent to determine blood lead concentration by the Inductively Coupled Plasma Mass Spectrometry (ICP‐MS 7700 Series; Agilent Technologies, Danbury, CT).

Serum total cholesterol, triglycerides, and high‐density lipoprotein cholesterol concentrations were measured enzymatically by an autoanalyzer (Konelab 60i; Thermo Scientific, Vantaa, Finland) using commercial kits (Konelab, Thermo Scientific). Low‐density lipoprotein cholesterol was calculated with the Friedewald formula.

Statistical Analysis

Data are demonstrated as mean±standard deviation for normally distributed continuous variables, median (range) for skew‐distributed continuous variables, and frequencies for categorical variables. Pearson chi‐square test was performed for the comparison of categorical variables. Means of normally distributed continuous variables were compared by independent sample t test. Correlation was tested with Spearman's rank order or Pearson correlation coefficient where appropriate. Linear regression analysis was performed for determining the factors affecting aortic strain and distensibility. Skewed variables were log transformed before performing regression analysis. Data for age, SBP, duration of exposure to lead, lead levels, renal function, body mass index, cigarette smoking, and lipid levels were put into equation. SPSS for Windows version 15.0 (SPSS Inc, Chicago, IL) was used for analysis and a two‐sided P value <.05 was considered significant.

Results

Demographic features of the study patients and controls are presented in Table 1. There was no significant difference in demographic features between the groups with lead exposure and those without. There was no significant difference in left atrial diameter, LV diameter, LV ejection fraction, mitral inflow velocities, DT, and IVRT between the lead‐exposure group and controls. Transthoracic echocardiography parameters of patients are presented in Table 2.

Table 1.

Baseline Characteristics of Patients

	Lead Exposure (n=41)	Control (n=39)	P
Age, y	37.5±8.9	35.1±6.2	NS
Weight, kg	75.5±11.8	81.8±10.4	.021
Height, cm	170.6±5.4	169.6±6.8	NS
SBP, mm Hg	117.5±10.5	122±2.4	.018
DBP, mm Hg	75.4±8.7	76.5±2.3	NS
Pulse pressure, mm Hg	42.07±5.5	45.5±4.2	.005
Lead, µg/dL	45.4±26.3	1.2±1.1	<.001
Hemoglobin, g/dL	15.2±1.4	14.8±1.2	NS
Total cholesterol, mg/dL	168.4±38.3	180±9.7	NS
LDL cholesterol, mg/dL	93.9±30.9	103.5±13.01	NS
HDL cholesterol, mg/dL	43.1±7.3	50.5±8.1	<.001
Triglycerides, mg/dL	181.7±51.5	129.6±28.6	.040

Abbreviations: DBP, diastolic blood pressure; HDL, high‐density lipoprotein; LDL, low‐density lipoprotein; SBP, systolic blood pressure. NS, not significant. Bold values indicate significance.

Table 2.

Comparison of Echocardiographic Parameters of Lead Exposure and Control Group

	Lead Exposure (n=41)	Control (n=39)	P Value
LVEDD, cm	4.7±0.5	4.4±0.6	<.001
LVESD, cm	2.9±0.5	2.8±0.4	<.001
Ejection fraction, %	69.3±6.8	67.1±3.4	NS
E, m/s	0.84±0.15	0.83±0.10	NS
A, m/s	0.61±0.12	0.64±0.11	NS
E/A ratio	1.21±0.31	1.20±0.25	NS
DT, ms	195.8±29.2	196.3±19.3	NS
IVRT, ms	96.2±17.1	94.3±13.3	NS
Aorta diastolic diameter, cm	2.82±0.31	2.63±0.41	.028
Aorta systolic diameter, cm	3.08±0.37	2.94±0.39	NS
Aortic strain, %	9.4±4.5	12.4±4.2	.004
Aortic distensibility, cm2/dyn	0.45±0.21	0.55±0.20	.046

Abbreviations: DT, deceleration time; IVRT, isovolumetric relaxation time; LVEDD, left ventricular end‐diastolic diameter; LVESD, left ventricular end‐systolic diameter; NS, not significant. Bold values indicate significance.

High‐density lipoprotein (HDL) cholesterol level was significantly lower in the lead‐exposure group than in controls (43.1±7.3 vs 50.5±8.1, P<.001). Triglyceride level was significantly higher in the lead‐exposure group than in controls (181.7±51.5 vs 129.6±28.6, P=.040). There was no significant difference in low‐density lipoprotein cholesterol and total cholesterol levels. There was no significant correlation between any aortic elasticity parameters and lipid parameters.

The lead level was significantly higher in the lead‐exposure group than in controls (45.4 vs 1.2 µg/dL, P<.001). The median duration of lead exposure was two (1–25) years. Aortic strain and aortic distensibility were used for evaluating aortic elastic parameters. Aortic strain (9.4%±4.5% vs 12.4%±4.2%, P=.004) and aortic distensibility (0.45±0.21 cm²/dyn vs 0.55±0.20 cm²/dyn, P=.046) were decreased in the lead‐exposure patients than in controls. Distribution of aortic strain between lead‐exposure patients and controls are shown in the Figure.

Figure 1.

Distribution of aortic strain in patients with lead exposure compared with controls.

There was a negative significant weak correlation between aortic strain and (r=−0.294, P=.008) lead levels. There was no significant correlation between aortic distensibility and any other echocardiographic parameters.

The factors affecting aortic strain were put into an equation for multivariate linear regression analysis and determined. Results revealed that only lead and HDL levels were independent factors of aortic strain.

Discussion

The relationship between lead exposure and arterial hypertension has been studied since the 1920s. It is commonly accepted that chronic exposure to lead may cause arterial hypertension.8

Similar molecular mechanisms are involved in the development of essential hypertension and hypertension caused by chronic lead exposure.9 The relationship between exposure to lead, development of arterial hypertension, and organ complications is poorly recognized. Poreba and colleagues found significant linear correlations between blood lead concentration and end‐organ complications in patients with arterial hypertension and chronic lead exposure. Cardiovascular complications such as LV hypertrophy, LV diastolic dysfunction, increased intimal‐media thickness, abnormal variability of BP, and increased local arterial stiffness were more frequently seen in patients with arterial hypertension occupationally exposed to lead than in hypertensive patients with no lead exposure.10

Hypertension can cause structural and functional changes in the aorta. Although the mechanism of increased aortic stiffness in hypertension is unclear, structural changes of the arterial walls, such as hypertrophy of the arterial media by increasing extracellular matrix and hypertrophy of tunica media that impairs arterial elastic parameters, may be caused by stress as a result of high pressure on the arterial walls in hypertension.11, 12

In this study, we evaluated aortic elastic parameters in normotensive workers occupationally exposed to lead. We showed that aortic elastic parameters were impaired in the lead‐exposure group. We found a significant correlation between blood lead concentrations and aortic elastic parameters and also a significant correlation between the duration of exposure. Endothelial dysfunction caused by lead exposure may be one of the possible mechanisms in impaired aortic elastic parameters.

Lead exposure may cause acute or chronic renal failure. Nephropathy caused by chronic lead exposure is consistent with progressive interstitial nephritis.13 It is manifested by a reduced glomerular filtration rate. Lead exposure may be related to hypertension by these mechanisms. However, patients with acute and chronic renal failure were excluded from the study.

Study Limitations

One of the limitations of our study was length of time of lead exposure. Median exposure time was 2 years in our study and it was a low‐exposure time. In addition, we used office BP measurements to detect hypertension. Because we did not perform ambulatory BP monitoring in this study, the patients with masked and white‐coat hypertension could not be excluded.

Conclusions

The present study showed that lead exposure may contribute to impairment of aortic elasticity and the vascular system. This impairment may develop before overt hypertension in workers exposed to lead.

J Clin Hypertens (Greenwich). 2014;16:790–793. © 2014 Wiley Periodicals, Inc.