Experimental Gerontology 58 (2014) 8–13

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Blood levels of lead, cadmium, and mercury in the elderly living in institutionalized care in the Czech Republic Jolana Rambousková a,⁎, Andrea Krsková b, Miroslava Slavíková a, Mája Čejchanová b, Milena Černá b,c a b c

Centre for Research of Diabetes, Metabolism and Nutrition, Department of Nutrition, Third Faculty of Medicine, Charles University in Prague, Ruská 87, 100 00 Prague 10, Czech Republic Environmental and Population Health Monitoring, National Institute of Public Health, Šrobárova 48, 100 42 Prague 10, Czech Republic Department of General Hygiene, Third Faculty of Medicine, Charles University in Prague, Ruská 87, 100 00 Prague 10, Czech Republic

a r t i c l e

i n f o

Article history: Received 1 November 2013 Received in revised form 4 July 2014 Accepted 8 July 2014 Available online 9 July 2014 Section Editor: Diana Van Heemst Keywords: Heavy metals in blood Lead Cadmium Mercury Institutionalized elderly

a b s t r a c t Background: There is limited research examining the chemical load of toxic metals in the elderly. The aim of the present study was two-fold: to determine the body burden of lead, cadmium and mercury in association with age, gender, locality, lifestyle factors and potential health impacts among this population and to compare the values with blood values from the general Czech population aged 18–64 years. Methods: Lead, cadmium and mercury were examined in the blood of institutionalized senior citizens (46 males, 151 females aged 61–100 years) from two localities in the Czech Republic (Prague and Teplice) from 2009 through 2011. Measurements were made using inductively coupled plasma mass spectrometry (Pb, Cd) and a single purpose spectrometer AMA 254 (Hg). Results: Geometric means (GM) of whole blood lead (B-Pb), cadmium (B-Cd) and mercury (B-Hg) levels were 25.3 μg/l, 0.55 μg/l and 0.21 μg/l, respectively. No age-related differences were found for B-Pb and B-Cd levels but a negative correlation with age was observed for B-Hg levels (p = 0.04). B-Pb levels in men were significantly higher than in women (GM 29.9 μg/l vs. 24.1 μg/l). B-Cd was significantly higher in women (GM 0.57 μg/l) than in men (0.50 μg/l) (p = 0.007) and in smokers (GM 1.29 μg/l) than in nonsmokers (GM 0.53 μg/l) (p = b0.001) and in seniors from Prague (GM 0.60 μg/l) compared to those from Teplice (GM 0.43 μg/l) (p = b 0.001). Seniors with a history of chronic kidney disease, stroke and those using psycho-pharmaceuticals had higher B-Pb levels (p = 0.008, 0.04 and 0.05, resp.), seniors diagnosed with atherosclerosis had higher B-Cd levels (p = 0.002) and seniors using psycho-pharmaceuticals had higher B-Hg levels (p = 0.07). B-Hg levels were also positively correlated with blood albumin levels (p = 0.015). Conclusions: This study provides data on levels of heavy metals in a group of elderly people. Such information is very scarce. Associations with diseases should be the subject of further investigation. © 2014 Elsevier Inc. All rights reserved.

1. Introduction Toxic metals such as lead, mercury and cadmium are ubiquitous components of the natural environment; but are also associated with environmental pollution, mostly linked to human activities such as industry, traffic and agricultural practice. The general population has been exposed to these toxins for many decades. Exposure to heavy metals is associated with a multitude of adverse health effects. These health risks tend to be greater in vulnerable population groups such as pregnant women, developing infants and small children (Al-Saleh et al., 2008; Chaumont et al., 2013; Landrigan et al., 2004; De Burbure et al., 2006). The elderly have also been identified as a group susceptible to environmental exposure (Risher et al., 2010). Aging is associated with

⁎ Corresponding author. E-mail address: [email protected] (J. Rambousková).

http://dx.doi.org/10.1016/j.exger.2014.07.002 0531-5565/© 2014 Elsevier Inc. All rights reserved.

important changes in body constitution and physiological functions. These changes may influence the toxic effects of heavy metals. Some heavy metals, mainly lead, mercury and cadmium can accumulate in the human body; this results in an increasing load with increasing age (Baecklund et al., 1999). Continuous long-term exposure or even lifelong exposure, to certain heavy metals may be accompanied by chronic diseases and adverse health effects that only manifest later in life. Recent epidemiologic studies have reported that environmental exposure to lead and cadmium has an exposure-related association with several diseases (e.g. hypertension, peripheral artery disease, brain dysfunction and cognitive impairment), the incidence of which increases with age (Elliot et al., 2000; Jarup et al., 1998; Lee et al., 2006; Nash et al., 2003; Satarug et al., 2003). Heavy metal exposure is considered to be one risk factor for cardiovascular disease and represents an increasing worldwide health problem (Alissa and Ferns, 2011). Cadmium is known to exert toxic effects on the kidney at low doses, without a demonstrable threshold (Ginsberg, 2012). The aging process results in a

J. Rambousková et al. / Experimental Gerontology 58 (2014) 8–13

rapid increase in bone demineralization, especially in women after menopause; this natural process can be exacerbated by kidney damage associated with chronic release (from storage in kidneys and liver) as well as exposure to cadmium (Verougstraete et al., 2003). Additionally, Cd and its compounds are classified, by the International Agency for Research on Cancer (IARC), as Group 1 agents (Group 1: The agent (mixture) is carcinogenic to humans.) for lung cancer, though lung cancer is probably more of a local effect in the lung, rather than general carcinogenicity. However there are significant relationships between bladder, prostate and endometrial cancer and blood cadmium levels in studies reported by the IARC (2012). The health status of the elderly population is important, especially in countries where the elderly population is rapidly increasing (Park et al., 2013; Risher et al., 2010). The Czech Republic is one of the nations in which the number of inhabitants over 65 years old is rising quickly (Křížová et al., 2010). In 2011, nearly 16% of the Czech population was 65 or older (Janečková et al., 2013) and the upward trend is expected to continue for decades to come. This upward trend could negatively impact the health status of the elderly population and may create a growing need for health promotion programs for the elderly. Knowledge of human exposure to environmental pollutants is an essential step that should precede any proposals for an intervention program. Currently, human biomonitoring (HBM) represents the best way to assess population exposure to environmental chemicals (Angerer et al., 2007). Since 1994, HBM has become an integral part of the national Environmental Health Monitoring System in the Czech Republic (Kliment et al., 2000). The project continuously monitors selected toxic and beneficial elements in the blood and urine of blood donors and children (Černá et al., 1997). However, HBM data concerning the elderly population are sporadic (Baecklund et al., 1999; Nordberg et al., 2000a, 2000b; Olsén et al., 2012). To learn more about the chemical load of toxic elements in the Czech elderly, the HBM approach has been applied as part of a larger project entitled The Nutritional Status Assessment of Elderly People in Institutional Care (Rambousková et al., 2013b). The goal of this project was to document blood levels of lead, cadmium and mercury in the elderly population, relative to age, gender, smoking habits, nutritional status, and region. An additional goal was to assess levels of toxins (Pb, Cd, and Hg) together with levels of beneficial elements in the elderly population (Rambousková et al., 2013a) and look for associations with specific chronic diseases which are common in elderly populations.

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informed consent. The information regarding personal data, lifestyle and other variables (marital status, education, employment, last job, health status of subjects, medical condition and medication, use of supplements, smoking habits etc.) was obtained using a guided interview and from personal medical records. Anthropometric measurements (weight, height, body mass index (BMI), waist circumference, triceps skinfold thickness) were completed in cooperation with nursing staff. The most common health issues recorded among the participants were ischemic heart disease (63.3%), hypertension (67.4%), diabetes mellitus (30.5%), atherosclerosis (27.8%), chronic kidney disease (19.8%), osteoporosis (17.6%) and Parkinson's disease (6.6%). 2.2. Blood sampling and analyses Blood samples were taken by skilled health personnel using standard protocols consistent with that used in the Czech human biomonitoring study (Černá et al., 2007). Blood was collected in metal-free tubes to avoid external contamination. S-Sarsted Monovette® tubes containing heparin as the anticoagulant and appropriate siliconized needles were used. Specimens were frozen at −18 °C until analysis. 2.2.1. Analyses 2.2.1.1. Sample preparation. Blood samples were mineralized before analysis with a mixture of concentrated nitric acid and hydrogen peroxide in a MEGA 1200 (Milestone) microwave oven equipped with a FAM 40 evaporation rotor to diminish the risk of external contamination. After mineralization, the solution was evaporated to a volume of approximately 0.1 ml and diluted with demineralized water to a final volume of 5 ml. Prior to analysis, samples were diluted with 1% (v/v) nitric acid to a volume two and a half times the original. An internal standard (mixture of In and Re; final concentration in samples was 10 μg standard/l) was added to all samples and standard solutions. 2.2.1.2. Determination of Pb, Cd, and Hg. Inductively coupled plasma mass spectrometry (ICP-MS) was used for the determination of Cd and Pb in mineralized blood samples. Measurements were carried out on a Perkin Elmer quadrupole ICP-MS Elan DRC-e (Perkin Elmer SCIEX Instrument, Canada). Isotopes and internal standards chosen for the determination of individual elements and their limits of detection and quantification are given in Table 1.

2. Material and methods 2.1. Study design and study subjects The study ran from 2009 through 2011. From 26 social care (eldercare) institutions in the capital city of Prague and from 6 social care institutions in a town in Northern Bohemia (Teplice) a total of 11 institutions were randomly selected by computer (9 from Prague, 2 from Teplice). Altogether 1069 subjects from the chosen institutions, aged 61 years or older, participated in the whole project. Blood samples were obtained from every fifth individual from an alphabetical list, and were tested for heavy metals (lead, cadmium, mercury). The same blood samples were also used to determine the levels of selected beneficial trace (selenium, copper, zinc and manganese) elements (Rambousková et al., 2013a). Additionally, biochemical parameters (albumin, prealbumin, transferrin, urea and creatinine) were analyzed using a second blood sample (Rambousková et al., 2013b). The analysis of heavy metals was completed for 197 elderly (46 male and 151 female) living in institutionalized care, mean age 83.6 (male 80.8 and female 84.5) years, there were 11 current smokers (mean age 73.3) and 186 were non-smokers (mean age 84.2). The study was approved by the Ethics Committee of the Third Faculty of Medicine, Charles University in Prague. All participants in the study were informed about the planned examination and gave written

2.2.1.3. Determination of mercury. Determination of mercury was completed directly, without mineralization, using a single purpose AMA 254 (Advanced Mercury Analyzer, Altec Praha, CZ) spectrometer. 100 μl of sample was introduced into the boat of the AMA 254 analyzer, dried for 60 s, combusted in a stream of oxygen and decomposed for 100 s on a catalytic column at 750 °C. The mercury vapor was trapped quantitatively on the surface of a gold amalgamator. The mercury, preconcentrated in this way, was then completely evaporated at 900 °C into the optical cell system and measured at 253.7 nm. The limit of detection (LOD) was 0.1 μg/l. 2.2.1.4. QA/QC. The accuracy of the measurement was checked using certified reference material of whole blood (Seronorm™ Trace Elements Whole Blood L-1 and L-2; SERO, Norway).

Table 1 Isotopes and internal standards chosen for the determination of lead and cadmium in blood using ICP-MS, limits of detection (LODs) and quantification (LOQs). Element

Measured isotopes

Internal standard

LOD μg/l

LOQ μg/l

Lead Cadmium

Sum of 206Pb+; 207Pb+; 208Pb+ Sum of 111Cd+; 114Cd+

Re In

0.08 0.01

0.27 0.05

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The measuring laboratory regularly participated in Round Robin Tests organized by the IAEA, IMEP, University of Erlangen. All determined values of elements in the study were in good agreement with declared values listed in Table 2 (see more in Čejchanová et al., 2012).

(Table 4). A positive correlation was found between B-Cd and atherosclerosis (p = 0.002), (Table 6).

2.3. Statistical analysis

B-Hg levels (GM 0.21 μg/l) did not show any difference relative to gender and locality; the only negative correlation was found for age (p = 0.04). Smokers had lower B-Hg levels compared with nonsmokers, but the difference was not significant (p = 0.095). No associations between B-Hg levels and diseases recorded on the medical history and questionnaire were observed except for the use of psychopharmaceuticals (p = 0.07). Additionally, B-Hg levels were positively associated with B-Se levels (p = 0.001) and with albumin levels (p = 0.015) (Rambousková et al., 2013b), (Tables 4–6 and Fig. 1).

Since the distribution of heavy metals in blood is log-normal (Kolmogorov–Smirnov test) the concentrations were characterized using medians, the 25th to 75th percentile ranges and geometric means (GM) transformed using the natural logarithm. The two-sample Wilcoxon test was used to test the differences in metal levels between subgroups. The degree of association between two continuous variables was measured by Spearman's rank correlation coefficient. Multiple linear regression was used to assess the relationship between metal levels and demographic (age, gender, education level) and other (locality, body mass index, smoking status) characteristics. The stepwise model selection with backward elimination was performed (p b 0.20 for entry and p N 0.10 for removal of a particular independent variable). The association between selected diseases and heavy metal levels in blood was analyzed using logistic regression and reported as odds ratio (OR) estimates with 95% confidence intervals. p-Values of less than 0.05 were considered statistically significant. All statistical analyses were performed using SPSS software for Windows, version 19.0. 3. Results Whole blood lead, cadmium and mercury levels are shown in Table 3. None of the study participants had values of Pb and Cd below the respective limits of detection (LODs) and limits of quantification (LOQs); while 29 samples were below the LOD of Hg and another 18 samples were between the LOD and LOQ of Hg. No associations between B-Pb, B-Cd and B-Hg levels and education, employment and BMI were found. Factors influencing levels of heavy metals in the blood of institutionalized elderly are summarized in Tables 4–6. 3.1. Blood concentration of lead B-Pb was significantly higher in men than in women (GM 29.9 μg/l vs. 24.1 μg/l, p = 0.004). The association was on the borderline of statistical significance with age (p = 0.060); while no significant differences between smokers and nonsmokers were observed. A marginally positive association (p = 0.077) was found between B-Pb and B-Cd levels (Table 4). A positive association was found between B-Pb and chronic kidney disease (p = 0.008), stroke (p = 0.04) and the use of psychopharmaceuticals (p = 0.05). No difference in B-Pb levels between Prague and Teplice was observed (Tables 5 and 6). 3.2. Blood concentration of cadmium No association between B-Cd and age was found. B-Cd was significantly higher in women (GM 0.57 μg/l) (p = 0.007) and in smokers (GM 1.29 μg/l) than in nonsmokers (GM 0.53 μg/l) (p b 0.001). It should be noted that the number of smokers in our sample was very low (n = 11). We found a positive association between of B-Cd and B-Pb (Table 3). B-Cd was significantly higher in seniors from Prague (GM 0.60 μg/l) compared to those from Teplice (GM 0.43 μg/l) (p b 0.001),

3.3. Blood concentration of mercury

4. Discussion The main aim of this study was two-fold: to evaluate exposure to lead, cadmium and mercury in the elderly population of the Czech Republic and to assess if there were any relationships between the blood levels of these toxic metals and common chronic diseases recorded in the personal medical histories of the study participants. 4.1. Lead B-Pb levels in the elderly (GM 29.9 μg/l and 24.1 μg/l in men and women, respectively) were slightly higher than those found in blood donors aged 18–64 years [sample period 2009 (GM 23.0 and 15.3 μg/l in males and females, respectively)] (Annual report, 2009). Higher blood lead levels in the elderly, compared to the general population, would have been expected due to endogenous release of lead from bone. However, only a marginal association between B-Pb levels and age was observed in this study of the elderly, aged 61–100. The marginal association was contrary to most HBM studies carried out in general populations with much larger age ranges (Bjermo et al., 2013). Also, B-Pb levels determined in a group of US citizens, aged 80 years and older, were not markedly elevated compared to the general population (Vearrier and Greenberg, 2012). These results suggest that agedependency of B-Pb may occur only up to semi-old ages, maybe 60 or 70 years of age. B-Pb levels were significantly higher in men than in women. This gender-related difference has been observed in almost all previous studies in many different countries, including in the Czech Republic (Batáriová et al., 2006; Beneš et al., 2000; Bjermo et al., 2013; Christensen, 1995; Schulz et al., 2007; Wilhelm et al., 2004). The reason for gender difference has been partly explained by Skerfving et al. (1999) and Vahter et al. (2007). In our study seniors who smoked did not have significantly higher B-Pb levels compared to nonsmokers, although some HBM studies have found higher B-Pb levels in smokers than in nonsmokers (Baecklund et al., 1999; Bjermo et al., 2013). It is noteworthy that there were only 11 smokers (six men and five women) in our study group. Exposure to lead has been related to several diseases that are common in the elderly, one of which is hypertension (Hertz-Picciotto and Croft, 1993). The study by Telišman et al. (2001) indicated a significant B-Pb level-related increase in systolic and diastolic blood pressures, particularly with low-level Pb exposure. However, data presented in the literature are inconsistent. In the NHANES 1999–2006 study of the US

Table 2 Results of Round Robin Tests organized by the University of Erlangen-Nurnberg: G-EQUAS — blood, environmental level; results, tolerance range (μg/l). Organizer

Cd A

Cd B

Hg A

Hg B

Pb A

Pb B

EQUAS 43;2009

0.75 0.34–0.76 0.55 0.27–0.57

1.15 0.66–1.20 0.94 0.71–1.19

1.05 0.61–1.57 0.48 0.27–0.75

2.30 1.77–3.45 2.11 1.47–2.67

53.0 50.06–65.72 19.73 17.01–26.55

66.1 65.21–85.07 65.92 63.15–85.41

EQUAS 46;2010

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Table 3 Blood lead, cadmium and mercury in seniors (μg/l). Total

Prague

Teplice

Men

Women

Smokers

Non-smokers

Lead N GM 95% CI Median 25th–75th percentile

197 25.3 23.6–27.2 25.1 18.9–25.1

146 25.7 23.6–27.9 25.8 18.8–38.1

51 24.4 21.4–27.9 23.8 19.0–32.1

46 29.9⁎ 25.9–34.5 30.1⁎ 19.8–40.6

151 24.1 22.2–26.1 23.9 18.2–35.7

11 23.9 19.1–29.9 24.6 16.7–31.5

186 25.4 23.6–27.4 25.1 18.9–37.3

Cadmium N GM 95% CI Median 25th–75th percentile

197 0.55 0.51–0.60 0.52 0.39–0.52

146 0.60⁎ 0.55–0.66 0.56⁎

46 0.50 0.43–0.58 0.48 0.37–0.71

151 0.57 0.52–0.63 0.53 0.40–0.74

11 1.29⁎ 0.86–1.94 1.36⁎

0.41–0.76

51 0.43 0.37–0.51 0.44 0.30–0.59

0.71–2.22

186 0.53 0.49–0.57 0.52 0.38–0.71

Mercury N GM 95% CI Median 25th–75th percentile

178 0.21 0.18–0.24 0.25 0.14–0.38

132 0.20 0.17–0.24 0.23 0.13–0.38

46 0.23 0.18–0.30 0.28 0.16–0.43

44 0.22 0.16–0.30 0.31 0.14–0.44

134 0.21 0.18–0.24 0.23 0.14–0.38

11 0.16 0.08–0.32 0.18 0.09–0.31

167 0.21 0.18–0.25 0.25 0.14–0.39

N — number of samples; GM — geometric mean; 95% CI — 95% confidence interval. ⁎ p b 0.05 between Prague and Teplice, men and women, smokers and non-smokers.

population, blood lead levels were significantly associated with blood pressure but the effect differed according to race and gender (Scinicariello et al., 2011). In a group of elderly from Stockholm aged 75 +, no relationship was found between B-Pb levels and blood pressure (Nordberg et al., 2000a, 2000b). Similarly, in our study no correlation between B-Pb levels and hypertension recorded in the elderly was observed. In fact, the only health status related association was between B-Pb level and chronic kidney disease (n = 39, p = 0.008) and stroke (n = 42, p = 0.037). The same results were observed in a study by Spector et al. (2011) where lead exposure was detected as risk factor for chronic kidney disease. In addition, a prospective study on kidney failure (Sommar et al., 2013) also showed an association with lead. A review by Navas-Acien et al. (2007) pointed out a positive association between blood Pb levels and stroke mortality in general population. 4.2. Cadmium B-Cd levels reflected recent exposure to Cd. Like Nordberg et al. (2000a, 2000b), we did not find any relationship between B-Cd and age in our study group. Gender-related differences in B-Cd have been frequently observed with higher levels in women (Baecklund et al., 1999; Olsén et al., 2012; Son et al., 2009). In our study women also had higher B-Cd levels than men. However in our previous study (Batáriová et al., 2006) no significant differences in B-Cd levels between men and women were observed. Generally, B-Cd levels have been observed to be strongly influenced by smoking habits (Shaham et al., 1996). The difference between smokers (GM = 1.29 μg/l) and nonsmokers (GM = 0.53 μg/l) was also observed in this study. Human exposure to cadmium is accompanied by several adverse health effects; the most important being kidney damage, carcinogenicity and skeletal damage (Nawrup et al., 2010). Several studies have shown that damage Table 4 Spearman's correlations between toxic metals (Pb, Cd, Hg — current part of the study) and between toxic and trace elements (Zn, Se — Rambousková et al., 2013a) and between mercury and albumin in the blood of institutionalized elderly. Element

Spearman's correlated coefficient

p-Value

Hg–Se Cd–Mn Cd–Zn Pb–Zn Cd–Pb Hg–albumin

0.256 0.227 0.170 0.178 0.124 0.183

0.001 0.002 0.017 0.012 0.077 0.015

to the skeleton (osteoporosis) can be critically affected by cadmium exposure (Akesson et al., 2014; Jarup et al., 1998). Exposure to Cd has been associated with all-cause and cardiovascular disease (CVD) mortality in the U.S. population (Tellez-Plaza et al., 2012). However, in our study there was no positive association with osteoporosis or CVD, although there was an association with atherosclerosis (p = 0.002); a similar association was also published by Fagerberg et al. (2012). In addition to the positive association with B-Pb, B-Cd levels also had a positive correlation with B-Mn and B-Zn levels (p =0.002 and p = 0.02, respectively) (Rambousková et al., 2013a). 4.3. Mercury B-Hg levels mainly reflected methylmercury exposure linked to seafood and shellfish consumption (NRC, 2000). Comparing B-Hg levels in the elderly with those found in blood donors, sampled in the same year as elderly, the GM values observed in blood donors were more than twice as high (0.57 μg/l in men and 0.64 μg/l in women) (Annual report, 2009). An explanation of this difference may be related to the very low consumption of shell fish and sea food among seniors; however, actual fish consumption was not studied. Another explanation may be the inverse association between B-Hg levels and age of the senior population. A decrease of B-Hg with aging was reported by Sakamoto et al. (1993). An Austrian study showed that higher age (51–65 years) was associated with lower mercury blood content, but only in men (Gundacker et al., 2006). In the U.S. population, B-Hg levels increased with age, peaking between ages 50 and 59, and then declined with Table 5 Predictors of blood levels of lead, cadmium and mercury in institutionalized elderly. Dependent variable

N

Independent variable

B-Pb

197

B-Cd

197

B-Hg

178

Male gender Age Male gender Current smoking Locality Age Current smoking

p-Value

R2

0.25 (0.08 to 0.42) 0.010 (−0.0004 to 0.020) −0.24 (−0.42 to −0.07) 0.95 (0.62 to 1.28)

0.004 0.060 0.007 b0.001

0.04

−0.32 (−0.49 to −0.15) −0.023 (−0.045 to −0.001) −0.55 (−1.20 to 0.10)

b0.001 0.044 0.095

Regression coefficient (95% CI)

0.20

0.02

Data on lead (B-Pb), cadmium (B-Cd) and mercury (B-Hg) were log-transformed. R2 — adjusted coefficient of determination; reference categories are female for gender, non-smokers and former smokers for current smoking and Prague for locality.

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Table 6 Association of selected diseases prevalence and psycho-pharmaceutical use with blood values of lead, cadmium and mercury tested by logistic regression model. N*

Odds ratio

95% confidence interval

p-Value

Lead (n = 197) Atherosclerosis Chronic kidney disease Insufficiency Stroke Depression Psychopharmaceutical Use

56 39 42 23 119

1.52 2.76 2.12 1.26 1.78

0.82–2.84 1.30–5.84 1.05–4.31 0.53–2.99 1.00–3.17

0.186 0.008 0.037 0.600 0.050

Cadmium (n = 197) Atherosclerosis Chronic kidney disease Stroke Depression Psychopharmaceutical Use

56 39 42 23 119

2.38 0.90 0.88 1.80 1.23

1.36–4.18 0.49–1.66 0.49–1.61 0.92–3.53 0.75–2.03

0.002 0.728 0.683 0.087 0.415

Mercury (n = 178) Atherosclerosis Chronic kidney disease Stroke Depression Psychopharmaceutical Use

56 39 42 23 119

1.04 0.99 1.01 0.78 1.32

0.74–1.45 0.68–1.44 0.70–1.45 0.49–1.24 0.97–1.80

0.821 0.974 0.974 0.292 0.077

defined as a mercury containing protein important for mercury metabolism in the human body (Yun et al., 2013). 5. Conclusions Blood levels of Pb and Cd in our senior study group did not show any marked differences compared to the economically active Czech general population (blood donors) monitored during the same time period; however, levels of B-Hg were significantly lower in seniors. Gender differences were observed with higher B-Pb and lower B-Cd levels in men compared to women. Our data revealed that the elderly who suffered from atherosclerosis had higher B-Cd levels, while higher B-Pb levels were significantly associated with chronic kidney disease, stroke and use of psycho-pharmaceuticals. Higher B-Pb was also marginally associated with higher B-Cd levels. As far as we know, our study is the only one that presents data, regarding blood levels of heavy metals, obtained from the senior population of the Czech Republic, and studies from other countries are scarce. Competing interests

Odds ratios express the change of disease risk associated with unit change in natural logarithm of the respective heavy metal predictor variable. N* = number of persons with the specific diagnose.

The contributing authors collectively state that there are no conflicts of interest associated with the results or publication of this study.

advancing age (Caldwell et al., 2009). In our study, no association between age and gender was observed. Surprisingly, B-Hg levels were lower in smokers than in nonsmokers, but the difference was not statistically significant. Similar results were obtained in our previous HBM study (Batáriová et al., 2006). Olsén et al. (2012) also mentioned a negative relationship between B-Hg levels and current smoking. Exposure to mercury can manifest in multiple ways including renal, cardiovascular, and immunological changes (Holmes et al., 2009). For methylmercury, the most sensitive endpoint is central nervous system toxicity. Indeed, in our study we observed a marginal positive correlation between B-Hg levels and psycho-pharmaceutical use (p = 0.07). However, since the B-Hg levels in our group of elderly were relatively low, this finding could be coincidental. B-Hg levels in our study were positively correlated with albumin. Data on serum albumin in seniors have been recently published by Rambousková et al. (2013b). Additionally, albumin was recently

Acknowledgments

Fig. 1. The relationship between mercury and albumin concentrations in the blood of institutionalized elderly.

This study was supported by research grant IGA MZ ČR no. NS 99724/2008. The authors would like to thank Prague City Hall for support and to M.A. Marek Malý for his valuable contribution to the statistical analyses and statistical guidance. References Akesson, A., Barregard, L., Bergdahl, I.A., Nordberg, G.F., Nordberg, M., Skerfving, S., 2014. Non-renal effects and the risk assessment of environmental cadmium exposure. Environ. Health Perspect. 122, 431–438. Alissa, E.M., Ferns, G.A., 2011. Heavy metal poisoning and cardiovascular disease. J. Toxicol. http://dx.doi.org/10.1155/2011/870125 (Published online 2011 September 8). Al-Saleh, I., Coscun, S., Mashhour, A., Shinwari, N., El-Doush, I., Billedo, G., Jaroudi, K., AlShahrani, A., Al-Kabra, M., Mohamed, G.E.D., 2008. Exposure to heavy metals (lead, cadmium and mercury) and its effect on the outcome of in-vitro fertilization treatment. Int. J. Hyg. Environ. Health 211, 560–579. Angerer, J., Ewers, U., Wilhelm, M., 2007. Human biomonitoring: state of the art. Int. J. Hyg. Environ. Health 210, 201–228. Annual report of the CZ-HBM for the year 2009 http://www.szu.cz/topics/environmentalhealth/environmental-health-monitoring. Baecklund, M., Pedersen, N.L., Björkman, L., Vahter, M., 1999. Variation in blood concentrations of cadmium and lead in the elderly. Environ. Res. Sect. A 80, 222–230. Batáriová, A., Spěváčková, V., Beneš, B., Čejchanová, M., Šmíd, J., Černá, M., 2006. Blood and urine levels of Pb, Cd and Hg in the general population of the Czech Republic and proposed reference values. Int. J. Hyg. Environ. Health 209, 359–366. Beneš, B., Spěváčková, V., Šmíd, J., Čejchanová, M., Černá, M., Šubrt, P., Mareček, J., 2000. The concentration levels of Cd, Pb, Hg, Cu, Zn and Se in blood of the population in the Czech Republic. Cent. Eur. J. Public Health 8 (2), 117–119. Bjermo, H., Sand, S., Nälsén, C., Lundh, T., Babieri, H.E., Pearson, M., Lindroos, A.K., Jönsson, B.A.G., Barregård, L., Darnerud, P.O., 2013. Lead, mercury, and cadmium in blood and their relation to diet among Swedish adults. Food Chem. Toxicol. 57, 161–169. Caldwell, K.L., Mortensen, M.E., Jones, R.L., Caudill, S.P., Osterloh, J.D., 2009. Total blood mercury concentrations in the U.S. population: 1999–2006. Int. J. Hyg. Environ. Health 212, 588–598. Čejchanová, M., Wranová, K., Spěváčková, V., Krsková, A., Šmíd, J., Černá, M., 2012. Human bio-monitoring study — toxic elements in blood of women. Cent. Eur. J. Public Health 20 (2), 139–143. Černá, M., Spěváčková, V., Čejchanová, M., Beneš, B., Rössner, P., Bavorová, H., Očadlíková, D., Šmíd, J., Kubínová, R., 1997. Population-based biomonitoring in the Czech Republic - the system and selected results. Sci. Total Environ. 204, 263–270. Černá, M., Spěváčková, V., Batáriová, A., Šmíd, J., Čejchanová, M., Očadlíková, D., Bavorová, H., Beneš, B., Kubínová, R., 2007. Human biomonitoring system in the Czech Republic. Int. J. Hyg. Environ. Health 210, 495–499. Chaumont, A., Voisin, C., Deumer, G., Haufroid, V., Annesi-Maesano, I., Roels, H., Thijs, L., Staessen, J., Bernard, A., 2013. Associations of urinary cadmium with age and urinary proteins: further evidence of physiological variations unrelated to metal accumulation and toxicity. Environ. Health Perspect. 121 (9), 1047–1053. Christensen, J.M., 1995. Human exposure to toxic metals — factors influencing interpretation of biomonitoring results. Sci. Total Environ. 166, 89–135.

J. Rambousková et al. / Experimental Gerontology 58 (2014) 8–13 De Burbure, C., Buchet, J.-P., Leroyer, A., Nisse, C., Haguenoer, J.-M., Mutti, A., Šmerhovský, Z., Cikrt, M., Trcinska-Ochocka, M., Razniewska, G., Jakubowski, M., Bernard, A., 2006. Renal and neurologic effects of cadmium, lead, mercury, and arsenic in children: evidence of early effects and multiple interactions at environmental exposure level. Environ. Health Perspect. 114, 584–590. Elliot, P., Arnold, R., Cockings, S., Eaton, N., Jarup, L., Jones, J., Quinn, M., Rosato, M., Thornton, I., Toledano, M., Tristan, E., Wakefield, J., 2000. Risk of mortality, cancer incidence, and stroke in a population potentially exposed to cadmium. Occup. Environ. Med. 57, 94–97. Fagerberg, B., Bergström, G., Borén, J., Barregard, L., 2012. Cadmium exposure is accompanied by increased prevalence and future growth of atherosclerotic plaques in 64-old women. J. Intern. Med. 272, 601–610. Ginsberg, G.L., 2012. Cadmium risk assessment in relation to background risk of chronic kidney disease. J. Toxicol. Environ. Health A 75 (7), 374–390. Gundacker, C., Komarnicki, G., Zödl, B., Forster, C., Schuster, E., Wittmann, K., 2006. Whole blood mercury and selenium concentrations in a selected Austrian population. Sci. Total Environ. 372, 76–86. Hertz-Picciotto, I., Croft, J., 1993. Review of the relation between blood lead and blood pressure. Epidemiol. Rev. 15 (2), 352–373. Holmes, P., James, K.A.F., Levy, L.S., 2009. Is low-level environmental mercury exposure of concern to human health? Sci. Total Environ. 408, 171–182. IARC International Agency for Research on Cancer, 2012. Cadmium and cadmium compoundsAvailable http://monographs.iarc.fr/ENG/Monographs/vol100C/mono100C8.pdf. Janečková, H., Dragomirecká, E., Holmerová, I., Vaňková, H., 2013. The attitudes of older adults living in institutions and their caregivers to ageing. Cent. Eur. J. Public Health 21 (2), 63–71. Jarup, L., Berglund, M., Elinder, C.G., Nordberg, G.P., Vahter, M., 1998. Health effects of cadmium exposure — a review of the literature and a risk estimate. Scand. J. Work Environ. Health 24, 1–51. Kliment, V., Kubínová, R., Kazmarová, H., Kratzer, K., Šišma, P., Ruprich, J., Černá, M., Gregůrková, M., 2000. Five years of the system of monitoring the environmental impact on population health of the Czech Republic. Cent. Eur. J. Public Health 8 (4), 198–205. Křížová, E., Brzyski, P., Strumpel, Ch., Billings, J., Lang, G., 2010. Health promotion for older people in the Czech Republic in a European perspective. Cent. Eur. J. Public Health 18 (2), 63–69. Landrigan, P.J., Kimmel, C.A., Correa, A., Eskenazi, B., 2004. Children's health and the environment: public health issues and challenges for risk assessment. Environ. Health Perspect. 112 (2), 257–265. Lee, D.H., Lim, J.S., Song, K., Boo, Y., Jacobs Jr., D.R., 2006. Graded associations of blood lead and urinary cadmium concentrations with oxidative-stress-related markers in the U. S. population: results from the Third National Health and Nutrition Examination Survey. Environ. Health Perspect. 114 (3), 350–354. Nash, D., Magder, L., Lustberg, M., Sherwin, R.W., Rubin, R.J., Kaufmann, R.B., Silbergeld, E. K., 2003. Blood lead, blood pressure, and hypertension in perimenopausal and postmenopausal women. JAMA 289, 1523–1532. National Research Council (NRC), 2000. Toxicological Effects of Methylmercury. National Academy Press, Washington, DC. Navas-Acien, A., Guallar, E., Silbergeld, E.K., Rothenberg, S.J., 2007. Lead exposure and cardiovascular disease — a systematic review. Environ. Health Perspect. 115 (3), 472–482. Nawrup, T.S., Staessen, J.A., Roels, H.A., Munters, E., Cuypers, A., Richart, T., Ruttels, A., Smeets, K., Clijsters, H., Vangronsveld, J., 2010. Cadmium exposure in the population: from health risks to strategies of prevention. Biometals 23, 769–782. Nordberg, M., Winblad, B., Fratiglioni, L., Basun, H., 2000a. Lead concentrations in elderly urban people related to blood pressure and mental performance: results from a population-based study. Am. J. Ind. Med. 38 (3), 290–294. Nordberg, M., Winblad, B., Basun, H., 2000b. Cadmium concentration in blood in an elderly urban population. Biometals 13, 311–317.

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Olsén, L., Lind, P.M., Lind, L., 2012. Gender differences for associations between circulating levels of metals and coronary risk in the elderly. Int. J. Hyg. Environ. Health 215, 411–417. Park, H.Y., Kim, J.H., Lim, Y.H., Bae, S., Hong, Y.C., 2013. Influence of genetic polymorphisms on the association between phthalate exposure and pulmonary function in the elderly. Environ. Res. 122, 18–24. Rambousková, J., Krsková, A., Slavíková, M., Čejchanová, M., Wranová, K., Procházka, B., Černá, M., 2013a. Trace elements in the blood of institutionalized elderly in the Czech Republic. Arch. Gerontol. Geriatr. 56 (2), 389–394. Rambousková, J., Slavíková, M., Krsková, A., Procházka, M., Anděl, M., Dlouhý, P., 2013b. Nutritional status assessment of institutionalized elderly in Prague, Czech Republic. Ann. Nutr. Metab. 62 (3), 201–206. Risher, J.F., Todd, G.D., Meyer, D., Zunker, C.L., 2010. The elderly as a sensitive population in environmental exposures: making the case. Rev. Environ. Contam. Toxicol. 207, 95–195. Sakamoto, M., Nakano, A., Akagi, H., Kitano, T., Futatsuka, M., 1993. Difference by sex and age of mercury concentration in red blood cells. Nippon Eiseigaku Zasshi 48, 911–919. Satarug, S., Baker, J.R., Urbenjapol, S., Haswell-Elkins, M., Reily, P.E., Williams, D.J., Reilly, P. E., 2003. A global perspective on cadmium pollution and toxicity in nonoccupationally exposed population. Toxicol. Lett. 137, 65–83. Schulz, C., Conrad, A., Becker, K., Kolossa-Gehring, M., Seiwert, M., Seifert, B., 2007. Twenty years of the German Environmental Survey (GerES). Human biomonitoring — temporal and special (West Germany/East Germany) differences in population exposure. Int. J. Hyg. Environ. Health 210, 271–297. Scinicariello, F., Abadin, H.G., Murray, H.E., 2011. Association of low-level blood lead and blood pressure in NHANES 1999–2006. Environ. Res. 8, 1249–1257. Shaham, J., Meltzer, A., Ashkenazi, R., Ribak, J., 1996. Biological monitoring of exposure to cadmium, a human carcinogen, as a result of active and passive smoking. J. Occup. Environ. Med. 38 (12), 1220–1228. Skerfving, S., Bencko, V., Vahter, M., Schutz, A., Gerhardsson, L., 1999. Environmental health in the Baltic region — toxic metals. Scand. J. Work Environ. Health 25 (Suppl. 3), 40–64. Sommar, J.N., Svensson, M.K., Björ, B.M., Elmstål, S.I., Hallmans, G., Lundh, T., Schön, S.M.I., Skerfving, S., Bergdahl, I.A., 2013. End-stage renal disease and low level exposure to lead, cadmium and mercury; a population-based, prospective nested case-referent study in Sweden. Environ. Health 12, 9. Son, J.Y., Lee, J., Paek, D., Lee, J.T., 2009. Blood levels of lead, cadmium and mercury in the Korean population: results from the Second Korean National Human Exposure and Bio-monitoring Examination. Environ. Res. 109, 738–744. Spector, J.T., Navas-Acien, A., Fadrowski, J., Guallar, E., Jaar, B., Weaver, V.M., 2011. Associations of blood lead with estimated glomerular filtration rate using MDRD, CKD-EPI and serum cystatin C-based equations. Nephrol. Dial. Transplant. 26 (9), 2786–2792. Telišman, S., Jurasovič, J., Pizent, A., Cvitkoviš, P., 2001. Blood pressure in relation to biomarkers of lead, cadmium, copper, zinc, and selenium in men without occupational exposure to metals. Environ. Res. Sect. A 87, 57–68. Tellez-Plaza, M., Navas-Acien, A., Menke, A., Crainiceanu, C.M., Pastor-Barriuso, R., Guallar, E., 2012. Cadmium exposure and all-cause and cardiovascular mortality in the U.S. general population. Environ. Health Perspect. 120, 1017–1022. Vahter, M., Åkesson, A., Lidén, C., Ceccatelli, S., Berglund, M., 2007. Gender differences in the disposition and toxicity of metals. Environ. Res. 104, 85–95. Vearrier, D., Greenberg, M.I., 2012. Blood lead levels in the United States “oldest-old” population. Clin. Toxicol. (Phila.) 50 (9), 838–840. Verougstraete, V., Lison, D., Hotz, P., 2003. Cadmium, lung and prostate cancer: a systematic review of recent epidemiological data. J. Toxicol. Environ. Health B 6 (3), 227–255. Wilhelm, M., Ewers, U., Schulz, C., 2004. Revised and new reference values for some trace elements in blood and urine for human biomonitoring. Int. J. Hyg. Environ. Health 207, 69–73. Yun, Z., Li, L., Liu, L., He, B., Zhao, X., Jiang, G., 2013. Characterization of mercurycontaining protein in human plasma. Metallomics 5 (7), 821–827 (27).