Smoking habits and cadmium intake in Turkey

Tobacco was estimated to account over 4 million annual deaths in 1998 and deaths attributable to tobacco usage will rise to 8.4 million in 2020 (http://tobacco.who.int/en/advocacy/wntdzoola.html.) In Turkey, 74% of the males and 29% of the females are smoking, and each year, 150,000 deaths are associated with cigaret smoking. There are 4700 chemical compounds in cigaret smoke, including 43 carcinogens. Cadmium (Cd) is only one of these harmful chemicals in the cigaret. The level of cadmium in whole blood is a reliable index of extent of recent metal uptake. In this study, cadmium concentrations in fasting whole-blood samples, from 119 healthy subjects (58 males and 61 females), ranging in age from 17 to 77 yr, who were not occupationally exposed to cadmium were measured by graphite furnace atomic absorption spectrometry, which is the most widely used technique for the measurement of cadmium concentrations in the whole blood. The blood cadmium concentration of nonsmokers, ex-smokers, and smokers were compared. The blood cadmium concentration of female smokers were found to be highest (mean: 2.62±0.72; median: 0.90 ng/mL Cd) and that of nonsmokers lowest (mean: 0.67±0.57; median: 0.44 ng/mL Cd). For smokers, an analysis of smoking history exhibited significant correlations between the number of daily cigarets smoked and the blood cadmium concentration (r=0.54, p=0.001) and years of smoking and blood cadmium concentration (r=0.51, p<0.001). Cadmium intake from cigaret smoking was found to be higher that the intake from air and diet.     

Mutagenic effect of amniotic fluid from smoking women at term

Concentrated term amniotic fluid samples from 44 women smokers and 44 controls were investigated with respect to mutagenic effect in the Salmonella/mammalian-microsome mutagenicity test, using tester strains TA98 and TA100. Tests with freeze-dried specimens of term amniotic fluid showed increases in the number of revertant colonies over background values, regardless of smoking status. However, samples from heavy smokers produced a higher number of revertants than did samples from nonsmokers in several experiments with tester strain TA98. The increase was statistically significant, using either total tar content or number of cigarettes smoked to identify heavy smokers. Experimental series with tester strain TA100 also resulted in higher group means for heavy smokers than for nonsmokers, but the difference was not statistically significant with the concentrations used in this assay. We conclude that heavy smokers may expose their unborn children to mutagenic substances.     

Simultaneous Determination of Cd, Pb, Cu, Zn, and Se in Human Blood of Jordanian Smokers by ICP-OES

A total of 73 blood samples (56 from smokers and 17 from nonsmokers) were collected to determine the concentrations of selected heavy metal in the whole blood of smokers and nonsmokers living in and around the city of Amman, Jordan. Analysis of heavy metals in the whole blood samples of various groups took in consideration the number of cigarettes smoked per day. The analysis of blood samples was carried out using inductively coupled plasma optical emission spectrometry. This study aimed to evaluate the blood metal levels in smokers and nonsmokers and to assess the influence of smoking cigarettes on blood metal levels. The results were compared with those from a control group. The results indicated that the average concentrations of cadmium (Cd), lead (Pb), copper (Cu), zinc (Zn), and selenium (Se) were 0.0313, 0.344, 2.328, 3.214, and 0.332 mg/L, respectively. Statistical analysis of results indicated that these average concentrations were significantly higher compared with the average concentrations in nonsmokers (P < 0.05). Moreover, the correlations between blood metal and other blood metal levels in smokers, the correlations between blood metal and other blood metal levels in nonsmokers, and the correlations between blood metal concentration in smokers and its concentration in nonsmokers were calculated. The standard reference material (blood serum National Institute of Standards and Technology 1598) and the quality control were used to validate the reliability of the method used for the estimation of heavy metals in blood samples. Results revealed that there was an agreement between the certified values and the measured values.     

Effects of zinc, copper, and selenium on placental cadmium transport

The objective of the present study was to evaluate the potential effects of zinc, copper, and selenium on placental cadmium transport. From November 2002 through January 2003, a total of 47 healthy pregnant women from Da-Ye City, Hubei Province in Central China participated in the study. Their age, parity, gestational age, pregnancy history, and lifestyle data were obtained by questionnaire interview. The placental, whole-blood, and cord blood levels of cadmium were determined by inductively coupled plasma mass spectrometer (ICP-MS), whole-blood zinc was measured by flame atomic absorption spectrometry (F-AAS), whole-blood copper by ICP-MS, and selenium was by atomic fluorescence spectrophotometry (AFS). The cord blood cadmium concentration (0.020-1.48 microg/L) was significantly lower than in maternal blood (0.80-25.20 microg/L, p<0.01). The placental cadmium concentration was from 0.082 to 3.97 microg/g dry weight. Multiple linear regression analysis indicated that lower levels of maternal blood copper were significantly associated with higher cadmium concentrations in cord blood. Placental cadmium in women with lower levels of maternal blood zinc was significantly higher than in those with normal zinc levels. The placental cadmium level in women with lower whole-blood selenium was significantly lower than in subjects with normal selenium levels. It was concluded that the essential elements copper, selenium, and zinc might significantly affect placental cadmium transport.     

Socio-demographic characteristics and lifestyle habits of pregnant women smokers

The aim of this study was to describe anthropometric, clinical, socio-demographic characteristics and lifestyle habits of pregnant smokers in comparison to pregnant nonsmokers. During years 1999-2003, 1,435 pregnant smokers and 4,772 pregnant nonsmokers were interviewed after delivery with a questionnaire. They were recorded clinical, anthropometric and socio-demographic data, smoking status, labor outcome, maternal and fetal hemoglobin concentrations for each patient. The two groups were comparable in anthropometric and clinical characteristics, duration of pregnancy and mode of delivery, except for birth weights, which were significantly lower in newborns of smokers. Maternal hemoglobin concentrations were significantly lower in smokers, but fetal hemoglobin concentrations were significantly higher in babies of smokers. The proportion of pregnant women who smoked during pregnancy was higher among urban women, among women with lower educational level and among unemployed subjects in comparison with nonsmokers. The pregnant women who smoked during pregnancy were more often caffeine and alcohol consumers. To further reduce smoking during pregnancy it is important to continue to promote smoking cessation among teenagers.     

Evaluation of Essential Trace and Toxic Elements in Scalp Hair Samples of Smokers and Alcohol User Hypertensive Patients

The incidence of hypertension has been associated to cigarette smoking and consumption of alcohol. In the present study, trace and toxic elements were determined in scalp hair of patients diagnosed with hypertension who are smokers and habitual alcohol drinkers living in Dublin, Ireland. These results were compared with age- and sex-matched healthy, nonsmokers, nondrinking controls. The concentrations of trace and toxic elements were measured by inductively coupled plasma atomic emission spectrophotometer after microwave-assisted acid digestion. The validity and accuracy of the methodology were checked using certified reference material (NCS ZC 81002b) and by the conventional wet acid digestion method on the same certified reference material and on real samples. The recovery of all the studied elements was found to be in the range of 97.5%–99.7% in certified reference material. The results of this study showed that the mean values of cadmium, copper, iron, nickel and lead were significantly higher in scalp hair samples of both smoker and nonsmoker hypertensive patients than referents (P < 0.001); whereas, the concentration of zinc was lower in the scalp hair samples of hypertensive patients of both genders. The deficiency of zinc and the high exposure of trace and toxic metals as a result of cigarette smoking and alcohol consumption may be synergistic with risk factors associated with hypertension.     

Blood and placental concentrations of cadmium, lead, and mercury in mothers and their newborns

Placental transfer of cadmium, lead and mercury was studied under the conditions of environmental exposures of pregnant women to these heavy metals. Fifty pregnant women from industrial area and a similar control group from a semirural area were examined. Cadmium, lead and total mercury levels were determined in maternal erythrocytes and plasma, in placenta, and in erythrocytes and plasma of umbilical cord blood using atomic absorption spectrophotometry. Except for the cadmium plasma concentration in the control area, levels of the three metals were higher in maternal than in cord blood. The mean plasma values (arithmetic mean) of cadmium, lead, and mercury in industrial area were 0.53, 6.37, and 0.37 micrograms.100 ml-1 in maternal blood and 0.30, 4.82, and 0.31 micrograms.100 ml-1 in cord blood. Highest values of the correlation coefficients were found between the cadmium and mercury concentrations in maternal and cord blood erythrocytes. No striking effect of the place of residence of pregnant women on the heavy metal concentrations in biological materials could be found.     

Cadmium and mercury levels in saudi women and its possible relationship with hypertension

The association between elevated blood pressure and blood cadmium and mercury levels was examined (2001–2002) in 185 Saudi women previously selected for a case-control study of lead and hypertension risk. Blood pressure was measured twice according to the World Health Organization recommendations. Cadmium and mercury were determined with graphite furnace and hydride system-atomic absorption spectrometry, respectively. Mean blood cadmium concentrations were 0.874±0.995 μg/L in hypertensive and 0.785±0.665 μg/L in controls. While blood mercury concentrations for hypertensives and controls were 3.506±3.617 μg/L and 3.687±3.186 μg/L, respectively. Participants were classified according to the median of blood cadmium and mercury levels. After adjustment for potentially confounding variables, the final logistic regression analyses revealed that women with blood cadmium ≥0.627 μg/L were 3.934 times were more likely to be hypertensive than those with blood cadmium levels <0.627 μg/L, although this was marginally significant (p=0.098). This was likely the result of the small number of subjects, resulting in the weak power to detect a strong significant difference between hypertensives and control cases. On the other hand, the final regression model showed no association between hypertension and mercury. However, this finding should not be conclusive because of the inappropriate choice of the biomarker indicator. Nevertheless, our study supports the hypothesis that exposure to cadmium might increase the risk of hypertension.     

A cross-sectional survey of cadmium biomarkers and cigarette smoking

Cadmium contamination of tobacco may contribute to the health hazards of cigarette smoking. The 2005–2012 United States National Health and Nutrition Examination Survey data provided a unique opportunity to conduct a cross-sectional survey of cadmium biomarkers and cigarette smoking. Among a sample of 6761 participants, we evaluated mean differences and correlations between cadmium biomarkers in the blood and urine and characteristics of never, former and current smokers. We found statistically significant differences in mean cadmium biomarker levels between never and former smokers as well as between never and current smokers. In current smokers, duration in years had a higher correlation coefficient with urinary than blood cadmium levels. In contrast, number of cigarettes smoked per day had a higher correlation coefficient with blood than urinary cadmium levels. These data suggest that blood and urine cadmium biomarker levels differ by duration and dose. These findings should be considered in evaluating any association between cadmium and smoking related diseases, especially cardiovascular disease.     

Smoking does not influence cadmium concentrations in blood and urine in relatively high levels of environmental cadmium areas in Japan

We examined how the influence of smoking on blood and urinary cadmium (Cd) concentrations was modified by the level of environmental Cd. We measured blood and urinary Cd concentrations of 1134 men over 50 yr of age in three areas in Japan that were exposed to different levels of environmental Cd. Analysis of variance was used to compare Cd concentrations in blood and urine of smokers with those of nonsmokers living in the three areas. Correlation coefficients between the number of cigarets smoked per day or smoking indices (the number of cigarets smoked per day multiplied by the number of years smoked) and blood and urinary Cd concentrations were calculated. No significant difference in Cd concentrations between smokers and nonsmokers was observed in areas where the average Cd concentration in blood was over approx 2.4 ng/g, 2.0 μg/L in urine, and 2.3 μg/g creatinine in urine, respectively. Therefore, it was suggested that an influence of smoking on blood and urinary Cd concentrations was not observed in areas exposed to relatively high levels of environmental Cd.     

Maternal Cadmium Levels During Pregnancy and the Relationship with Preeclampsia and Fetal Biometric Parameters

Preeclampsia, which is caused by multiple factors, still remains one of the most serious complications of pregnancy. This study was designed to determine cadmium levels in women with preeclampsia compared to those of normotensive women. In this case-control study, maternal blood, umbilical cord blood, and placental cadmium levels were measured by an inductively coupled plasma mass spectrometry system in 51 women presenting consecutively with preeclampsia and 51 normotensive pregnant women. Groups were matched for maternal age, parity, and gestational age. Birth outcomes were recorded, such as gestational age at delivery, birth weight, and Apgar score. Median (interquartile range [IQR]) blood cadmium concentration was 1.21 μg/L (0.76–1.84 μg/L) and 1.09 μg/L (0.72–1.31 μg/L) in women with preeclampsia and normotensive, respectively; values for placental cadmium levels of women with preeclampsia and normotensive were 3.61 μg/kg (2.19–4.37 μg/kg) and 4.28 μg/kg (3.06–5.71 μg/kg), respectively. We observed a statistically significant increase in blood and placental cadmium levels in women with preeclampsia compared to healthy pregnant women. After adjusting for pre-pregnancy body mass index, maternal age, parity, gestational age at sample collection, and maternal calcium and magnesium levels, the odds ratio of having preeclampsia in the high tertile was markedly increased (odds ratio, 7.83 [95% CI, 1.64–37.26]) compared with the low tertile. Interestingly, there was no difference in the cadmium level in umbilical cord blood between the groups. Within the preeclamptic group, higher cadmium status was significantly associated with decreased birth weight. Our study suggested that elevated cadmium level in the maternal circulation could potentially increase the risk of preeclampsia. The results also demonstrate that higher cadmium status may contribute to fetal growth restriction in preeclamptic patients.     

Associations of alcohol consumption with blood pressure and serum lipids in Japanese female smokers and nonsmokers

Background: Alcohol intake and smoking have been reported to influence atherosclerotic progression.Objective: The purpose of this study was to determine whether the associations of alcohol intake with blood pressure (BP) and serum lipid concentrations are modified by smoking in Japanese women.Methods: Eligible subjects were healthy female Japanese workers aged 35 to <55 years who had received periodic health examinations at workplaces in Yamagata Prefecture in Japan. Subjects were classified as smokers or nonsmokers and subclassified into 3 subgroups based on average daily reported alcohol intake: nondrinkers, light drinkers (<15 g/d), and heavy drinkers (>-15 g/d). The means of each variable (systolic and diastolic BP [SBP and DBP, respectively] and serum concentrations of total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides) were compared among the 2 groups of smoking history and 3 subgroups of alcohol intake after adjusting for age and body mass index.Results: A total of 16,805 healthy women were enrolled (14,695 nonsmokers, 2110 smokers). In smokers, SBP was significantly higher in heavy drinkers than in nondrinkers, and DBP was significantly higher in light drinkers and heavy drinkers than in nondrinkers (all, P < 0.01). In nonsmokers, SBP was not significantly higher in light drinkers and heavy drinkers versus nondrinkers, and the difference in DBP between heavy drinkers and nondrinkers was significant (P < 0.01), but that between light drinkers and nondrinkers was not. In smokers but not in nonsmokers, serum TC concentration was significantly lower in heavy drinkers than in nondrinkers. In smokers and nonsmokers, LDL-C was significantly lower in light and heavy drinkers than in nondrinkers (all, P < 0.01), and serum HDL-C was significantly higher in light and heavy drinkers than in nondrinkers (all, P < 0.01). The differences in mean LDL-C between light and heavy drinkers versus nondrinkers were numerically greater in smokers than in nonsmokers.Conclusion: In this sample of women in Japan, serum LDL-C concentration was significantly lower in drinkers than in nondrinkers, and smoking might increase this association between alcohol intake and lowered LDL-C.     

Cadmium Exposure and Incidence of Diabetes Mellitus - Results from the Malm? Diet and Cancer Study

Background

Cadmium is a pollutant with multiple adverse health effects: renal dysfunction, osteoporosis and fractures, cancer, and probably cardiovascular disease. Some studies have reported associations between cadmium and impaired fasting glucose and diabetes. However, this relationship is controversial and there is a lack of longitudinal studies.

Objectives

To examine prospectively whether cadmium in blood is associated with incidence of diabetes mellitus.

Methods

The study population consists of 4585 subjects without history of diabetes (aged 46 to 67 years, 60% women), who participated in the Malmö Diet and Cancer study during 1991–1994. Blood cadmium levels were estimated from hematocrit and cadmium concentrations in erythrocytes. Incident cases of diabetes were identified from national and local diabetes registers.

Results

Cadmium concentrations in blood were not associated with blood glucose and insulin levels at the baseline examination. However, cadmium was positively associated with HbA1c in former smokers and current smokers. During a mean follow-up of 15.2±4.2 years, 622 (299 men and 323 women) were diagnosed with new-onset of diabetes. The incidence of diabetes was not significantly associated with blood cadmium level at baseline, neither in men or women. The hazard ratio (4^th vs 1^st quartile) was 1.11 (95% confidence interval 0.82–1.49), when adjusted for potential confounders.

Conclusions

Elevated blood cadmium levels are not associated with increased incidence of diabetes. The positive association between HbA1c and blood cadmium levels has a likely explanation in mechanisms related to erythrocyte turnover and smoking.     

Metals content in placentas from moderate cigarette consumers: correlation with newborn birth weight

Cigarette consumption during pregnancy produces deleterious effects in both, mother and fetus, some of them due to the presence of toxic elements in cigarette smoke, such as cadmium. Placenta constitutes a dual-purpose specimen for evaluating the pollutant burden exerted on the mother as well as on the fetus. The main objective of this study was to establish a correlation between placental concentration and distribution of some metal elements and birth weight of neonates delivered by mothers, who were either moderate smokers or nonsmokers. Forty nonsmoking and moderate smoking pregnant women paired per age, parity, weight, height and body mass index were selected. Smoking was assessed by self-reported cigarette consumption during pregnancy and urine cotinine concentration before delivery. Placental metal concentrations were evaluated by atomic absorption spectrometry (copper and cadmium) and neutron activation analysis (zinc and iron). Newborns from smokers had lower birth weights compared to infants from nonsmokers. Birth weights were correlated with placental cadmium concentrations in both, smokers and nonsmokers. Placental zinc and cadmium of smokers were mainly located at the maternal side and their levels were higher than those found in nonsmokers placentas. In addition, all metal nutrient/pollutant ratios were decreased in the smoker group. In this first study performed in our region, we found that moderate smoking mothers deliver neonates with decreased birth weight and highly correlated to placental cadmium concentration. Decreased metal nutrient/pollutant ratios, a condition here found in smokers, may indicate a placental dysfunction, contributing to impair birth weight.     

Intra- and inter-individual relationships between central and peripheral serotonergic activity in humans: a serial cerebrospinal fluid sampling study

Data are lacking concerning the longitudinal covariability and cross-sectional balance between central and peripheral 5-HIAA concentrations in humans and on the possible associations between tobacco smoking or post-traumatic stress disorder (PTSD) and CSF and plasma 5-HIAA concentrations. Using serial cerebrospinal fluid (CSF) and blood sampling, we determined the concentrations of 5-HIAA in CSF and plasma over 6 h, and examined their relationships in healthy volunteers and patients with PTSD-both smokers and nonsmokers. Patients with PTSD and healthy volunteers had very similar CSF 5-HIAA concentrations. Significant and positive correlations between CSF and plasma 5-HIAA levels were observed within individuals, but this CNS-peripheral 5-HIAA relationship was significantly reduced in smokers (nonsmokers: mean r = 0.559 +/- 0.072; smokers: mean r = 0.329 +/- 0.064 p < 0.038). No significant cross-sectional, interindividual correlation of mean CSF and mean plasma 5-HIAA was seen (r = 0.094). These data show that changes in CSF 5-HIAA levels within an individual over time are largely reflected in plasma 5-HIAA, albeit significantly less so in smokers. The present results therefore suggest that clinically, longitudinal determination of plasma 5-HIAA concentrations within an individual patient can be used to make inferences about relative changes in integrated CSF 5-HIAA concentrations. However, plasma 5-HIAA concentrations provide no significant information about absolute levels of the serotonin metabolite in the CSF.     

Cadmium,Lead, and Selenium in Cord Blood and Thyroid Hormone Status of Newborns

Cadmium (Cd), lead (Pb), and selenium (Se) concentrations in cord whole blood, sampled from 24 women at the time of delivery in a hospital in Tokyo in 2005, were determined by inductively coupled plasma mass spectrometry with a reaction cell. Signal enhancement caused by nonspectroscopic interference for Se was evident and the standard addition technique was essential for correcting the interference. Median concentration in cord bloods was 0.20 ng/g, 6.7 ng/g (0.67 μg/dL), and 191 ng/g for Cd, Pb and Se, respectively. Lead concentration was lower, whereas Se concentration was higher, than those reported in other countries. The trace element concentration was related to the levels of thyroid stimulating hormone (TSH) and free thyroxin (fT4) in the neonatal blood sampled at 4–6 days postpartum. A significantly negative correlation was observed between Cd concentrations in cord blood and TSH concentration in neonatal blood. The result indicated the possible effect of in utero Cd exposure on thyroid hormone status of newborns and that Cd exposure level should be assessed as a covariate in the survey on the relationship between in utero chemicals (e.g., PCBs) exposure and thyroid hormone status.     

Increased plasma concentrations of C9, C1-inhibitor and alpha 1-protease inhibitor associated with cigarette smoking

The association between various parameters of acute and chronic smoking status and plasma levels of three proteins, C9, C1-inhibitor (C1-INH) and alpha 1-protease inhibitor (alpha 1-PI) were determined for 49 male cigarette smokers and 49 age-matched nonsmokers (mean age = 32.2 years). The mean number of cigarettes smoked was 28.7 per day while the cumulative consumption was only 18.1 pack-years. Plasma levels of all three proteins were significantly higher in the smokers than nonsmokers. Plasma C9 and alpha 1-PI concentrations correlated with cumulative cigarette consumption and plasma nicotine concentrations. While C1-INH concentration did not correlate with either cumulative cigarette consumption or plasma nicotine concentration, it correlated significantly with serum thiocyanate concentration. No consistent correlation was found between plasma concentration of these proteins and parameters of pulmonary function.     

Increased aldosterone/renin quotient in obese hypertensive women: a novel role for low-density lipoproteins?

Obesity, especially visceral obesity, is strongly associated with arterial hypertension. Indeed, obesity hypertension has to be considered as the most common form of essential hypertension. However, the exact nature of the relationship between obesity and increased blood pressure remains poorly understood. Involvement of renin-independent mechanisms has been suggested in adrenal stimulation of aldosterone secretion in obese patients. This investigation examined the plasma levels of renin, aldosterone, insulin, and HDL and LDL in obese hypertensive and obese normotensive women. The group of hypertensive obese women showed significantly reduced plasma levels of renin and increased aldosterone/renin quotient (ARQ) compared to obese normotensive women. Plasma aldosterone levels were not significantly different between hypertensive and normotensive obese women. In addition, plasma levels of LDL-cholesterol in the hypertensive obese group were significantly increased in comparison to the obese normotensive group. No differences were observed in HDL-cholesterol or total cholesterol/HDL-C ratios between the two groups. We therefore examined the effect of LDL on angiotensin II-stimulated aldosterone release from human adrenocortical H295R cells. Treatment of adrenocortical cells with LDL led to a sensitization towards stimulation by angiotensin II, dramatically increasing angiotensin II-induced aldosterone production, so the increased aldosterone/renin ratio observed in the hypertensive group may be due to the enhanced LDL levels in these patients and/or other adipocyte-derived mineralocorticoid-stimulating factors.     

Reduced fetal, placental, and amniotic fluid PTHrP in the growth-restricted spontaneously hypertensive rat

Evidence implicates pivotal roles for parathyroid hormone-related protein (PTHrP) in stimulating cell growth and differentiation, placental calcium transport, and placental vasodilatation. As spontaneously hypertensive rat (SHR) fetuses are growth restricted compared with those of its normotensive control, the Wistar Kyoto (WKY) rat, we examined intrauterine PTHrP and total and ionic calcium concentrations in these rats. Fetal plasma PTHrP concentrations, but not total calcium concentrations, were lower in the SHR compared with WKY (P < 0.05). SHR placental concentrations of PTHrP were lower than in WKY (P < 0.03) and failed to show the increase observed in WKY near term (P < 0.05). PTHrP concentrations in amniotic fluid from SHR were not raised near term and were lower compared with WKY (P < 0.0005). The increased ionic calcium concentrations in amniotic fluid in the WKY near term (P < 0.05) were not detected in the SHR. Thus SHR fetal plasma, placental, and amniotic fluid PTHrP concentrations were reduced and associated with fetal growth restriction. We suggest that PTHrP may play a role in the etiology of both growth restriction during pregnancy and hypertension later in life.     

Is Cadmium Exposure Associated with the Burden,Vulnerability and Rupture of Human Atherosclerotic Plaques?

The general population is exposed to cadmium from food and smoking. Cadmium is a widely spread toxic pollutant that seems to be associated with cardiovascular diseases, although little is known if it contributes to the occurrence of atherosclerotic plaques and the process whereby plaques become vulnerable and are prone to rupture. We tested the hypotheses that cadmium exposure is associated not only with an increased subclinical burden of atherosclerotic plaques in different vascular territories and early signs of plaque vulnerability, but also with cadmium content and plaque-rupture in the clinical phase of the disease. Ultrasound technique was used to measure plaque prevalence and echogenicity in the carotid and femoral arteries in a population sample of women (n = 599) in whom blood cadmium was measured. In addition cadmium was measured in snap-frozen endarterectomies and whole blood obtained from patients who were referred to surgery because of symptomatic carotid plaques (n = 37). Sixteen endarterectomies were divided into three parts corresponding to different flow conditions and plaque vulnerability. In the population sample blood cadmium was associated with the number of vascular territories with plaques (p = 0.003 after adjustment for potential confounders). The cadmium concentrations in symptomatic plaques were 50-fold higher in plaque tissue than in blood. Cadmium levels in blood and plaque correlated, also after adjustment for smoking and other cardiovascular risk factors (p<0.001). Compared with the other parts of the plaque, the cadmium content was double as high in the part where plaque rupture usually occurs. In conclusion, the results show that cadmium exposure is associated with the burden of subclinical atherosclerosis in middle-aged women with different degrees of glucose tolerance, and that the content of cadmium in symptomatic plaques in patients is related to that in blood, but much higher, and preferentially located in the part of plaque where rupture often occurs.