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The association between blood pressure and blood cadmium in a Chinese population living in cadmium polluted area
e n v i r o n m e n t a l t o x i c o l o g y a n d p h a r m a c o l o g y 3 6 ( 2 0 1 3 ) 595–599
Available online at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/etap
The association between blood pressure and blood cadmium in a Chinese population living in cadmium polluted area Xiao Chen a,b , Guoying Zhu b , Lijian Lei c , Taiyi Jin b,∗ a b c
Department of Radiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China Institute of Radiation Medicine, Fudan University, Shanghai 200032, China School of Public Health, Fudan University, Shanghai 200032, China
a r t i c l e
i n f o
a b s t r a c t
Article history:
Cadmium exposure may be associated with high risk of hypertension. But inconsistent
Received 25 February 2013
results have been reported. In this study, the association of blood pressure (BP) with blood
Received in revised form
cadmium (BCd) and the possible influencing factors were investigated. A total of 181 per-
10 June 2013
sons (71 men and 110 women) living near a cadmium smelter participated in this study.
Accepted 15 June 2013
The participants completed a questionnaire and BP, BCd and related biochemical indicators
Available online 24 June 2013
were measured. The geometric mean of BCd was 3.84 g/L and 3.32 g/L for women and men. The systolic blood pressure (SBP) and diastolic blood pressure both increased with the
Keywords:
increasing of BCd. The BP in women was positively correlated with BCd (p < 0.05). The BCd
Cadmium
level of participants with hypertension was obvious higher (+28%) than those with normal
Blood pressure
BP. The prevalence of hypertension was increased with the increasing of BCd, in particular
Blood lipid
to women (2 = 3.896, p = 0.048). Cadmium level in blood was associated with elevation in blood pressure, especially for women. © 2013 Elsevier B.V. All rights reserved.
1.
Introduction
Cadmium (Cd) is a hazardous heavy metal that is widely distributed in the environment. It could accumulate in food, such as rice and vegetables. Food is one of major environmental source of Cd exposure for non-smoking population (Jarup, 2003). Long-term low level of oral Cd exposure may cause chronic damage to human body. The kidney, liver, bone, and cardiovascular systems are the most important organs for Cd toxicity (World Health Organization, 1992). An important toxicological feature of Cd is its long biological half-time (10–30 years) in humans (Nordberg, 1996).
∗
It has been shown that Cd exposure may be associated with stroke, heart failure and myocardial infarction (Everett and Frithsen, 2008; Peters et al., 2010; Tellez-Plaza et al., 2012). Studies in vivo have indicated that long-term high level of Cd exposure could induce elevation of blood pressure (Perry Jr. et al., 1977). Epidemiological studies also suggest that Cd exposure is correlated with the elevation of blood pressure (Tellez-plaza et al., 2008; Eum et al., 2008; Caciari et al., 2012). However, studies also demonstrate that there are no (Beevers et al., 1976; Swaddiwudhipong et al., 2010; Mordukhovich et al., 2012) or even a negative association (Staessen et al., 1984) between blood pressure and Cd exposure. In addition, Lee et al. (2011) reported that the association of Cd and
Corresponding author at: School of Public Health, Fudan University, 200032 Shanghai, China. Tel.: +86 21 64438121; fax: +86 21 64049847. E-mail addresses: chx [email protected], [email protected] (T. Jin). 1382-6689/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.etap.2013.06.006
596
e n v i r o n m e n t a l t o x i c o l o g y a n d p h a r m a c o l o g y 3 6 ( 2 0 1 3 ) 595–599
hypertension was only found in male and no association was found in female. Blood pressure is related with blood lipids level. It has been indicated that Cd may disturb lipids metabolism in vivo (Larregle et al., 2008). But we do know whether the hypertension caused by Cd is related with blood lipids level. This study tries to observe the association between blood Cd and blood pressure in a Chinese population living in a Cd polluted area. In addition, we also observe the effects of Cd exposure on blood lipids level.
2.3.
The blood pressure was measured twice on right wrist using electronic sphygmomanometer (Omron, Dalian, China) in a sitting position. Because wrist blood pressure measured by the electronic sphygmomanometer was higher than arm blood pressure measured by mercury sphygmomanometer. In this study, hypertension was regarded as diastolic pressure >95 mm Hg and or/systolic pressure >160 mm Hg or receipt of current antihypertensive treatment.
2.4.
2.
Materials and method
2.1.
Area and study population
Total 181 persons aged 40 years and older, living in a Cdcontaminated area, were recruited in this study. A smelter was located in this area and industrial wastewater was regularly discharged into the river near the factory. The concentrations of metals (Cd, Lead, and Copper) in the wastewater exceeded the levels of Chinese hygiene standards. The residents living in the polluted areas used the polluted river for irrigation from 1961 to 1995. The Cd concentration in rice was about 3.7 mg/kg and the main staple food in these areas was the rice that they produced from these fields. From 1996 onward, however, the residents stopped producing rice in these fields and began eating commercially available rice from other (non-polluted) areas (Cd in rice: 0.03 mg/kg). More detailed information has been provided previously (Wang et al., 2003). The participants in the study gave their informed consent and completed a questionnaire including information on medical and drug history, cigarette smoking, alcohol consumption and medical history of hypertension. Height and weight data were obtained to calculate body mass index (kg/m2 ). Samples of venous blood were collected from each participant for determination of Cd concentration and biochemical indicators. During this study, Declaration of Helsinki was followed. This study was carried out with the permission of the Ethics Committees of Fudan University.
2.2.
Blood pressure measurement
Lipids level measurements
Fasting blood triglyceride (TG), total cholesterol (TC) and high density lipoprotein (HDL) level were measured by automatic biochemical analyzer (Hitach7150, Japan).
2.5.
Statistical analysis
Database management and analysis were performed using SPSS11.5 (SPSS Inc, Chicago, IL, USA) and EPI INFO (Version 3.5.1, Centers for Disease Control and Prevention, Atlanta, GA, USA). Arithmetic means were compared by using one wayANOVA and Pearson correlation was applied to analyze the correlation of BP with BCd (log-transformed), height, weight and other biochemical indicators. The data were expressed as mean ± SD. The criterion significance level was set at p < 0.05.
3.
Results
3.1.
3.1. Characteristics of study population
The general characteristics of study population, the BCd concentration and lipids level were shown in Table 1. 61% of the participants were female. There were significant differences between men and women in height, weight and tobacco smoking (p < 0.05). The concentration of BCd in women was slightly higher than that in men. The systolic blood pressure (SBP) and diastolic blood pressure (DBP) in men were higher than those in women, but no significant differences were found. No obvious differences were found in blood lipids level between men and women.
Exposure assessment 3.2.
Collection of samples followed a strict protocol. Cd was measured as already described (Jin et al., 1998). Briefly, blood samples were collected in heparin tubes and stored frozen (−20 ◦ C) until analyzed. Cd content in blood (BCd) was measured by graphite-furnace atomic absorption spectrometry (GF-AAS, ShimadzuAA-670, Kyoto, Japan). Between and within bottle homogeneity testing was below 6% and 7%. For quality control, reference material (lyophilized whole human blood) with two certified concentration (9.6 ± 1.7 g/kg and 3.3 ± 0.9 g/kg) were analyzed. The obtained Cd concentrations were 11.1 ± 0.2 g/kg and 4.8 ± 0.3 g/kg. The detection limit of Cd in blood using this method was 0.05 g/L. BCd was used as measures of the exposure. BCd reflects Cd body burden (Diarmid et al., 1997), particularly in long term low level of exposure and after cessation of exposure.
BCd and blood pressure
The blood pressure, TG and TC were increased with the increasing of BCd in women (Table 2). Compared with the subjects with the lowest level of BCd, the SBP and DBP in the subjects with the highest level of BCd were increased by 8% and 4%, respectively, after adjusted for age and BMI. But no significant differences were found. Meanwhile, TG and TC increased by 30% and 17% in the people with the highest level of BCd compared with those with the lowest level of BCd. For men, the blood pressure, TG and TC level were higher in middle BCd group compared with other BCd group, but there was no significant difference. Consequently, men and women were divided into three groups according to the level of blood pressure (Table 3). The BCd, TG and TC of those persons with high blood pressure
597
e n v i r o n m e n t a l t o x i c o l o g y a n d p h a r m a c o l o g y 3 6 ( 2 0 1 3 ) 595–599
Table 1 – Characteristics of study population.
Age (years) Body weight (kg) Height (cm) Triglyceride (mmol/L) Cholesterol (mmol/L) High density lipoprotein (mmol/L) Systolic blood pressure (mm Hg) Diastolic blood pressure (mm Hg) BCda (g/L) Smoking ∗ a
Total (n = 181)
Women (n = 110)
Men (n = 71)
58.2 ± 10.8 62.67 ± 10.68 159.59 ± 7.48 2.20 ± 1.68 5.45 ± 1.08 1.32 ± 0.23 145.97 ± 18.30 90.04 ± 11.97 3.63 38 (21%)
57.4 ± 9.2 58.57 ± 8.51 155.51 ± 5.27 1.92 ± 1.31 5.47 ± 1.12 1.32 ± 0.21 143.41 ± 7.36 88.37 ± 11.21 3.84 0
59.8 ± 11.8 69.02 ± 10.64* 165.91 ± 5.84* 2.64 ± 2.06 5.41 ± 1.01 1.33 ± 0.25 149.97 ± 9.11 92.64 ± 12.71 3.32 38 (54%)*
P < 0.05, compared with women. Geometric mean.
Table 2 – Blood cadmium and blood pressure/blood lipid in women and men. BCd (g/L)
n
Age
SBP
DBP
TG
TC
HDL
Women
<2 2–5 >5
11 62 37
54.60 ± 6.48 56.45 ± 9.23 59.97 ± 9.28
138.91 ± 13.44 141.84 ± 16.83 147.35 ± 18.88
84.91 ± 7.80 87.18 ± 9.38 90.59 ± 13.10
1.73 ± 0.73 1.83 ± 1.00 2.28 ± 1.82
4.85 ± 0.74 5.35 ± 0.90 5.64 ± 1.42
1.30 ± 0.12 1.35 ± 0.22 1.31 ± 0.22
Men
<2 2–5 >5
15 35 21
58.33 ± 11.79 58.05 ± 13.61 58.33 ± 12.89
143.2 ± 17.00 154.0 ± 18.17 148.10 ± 21.18
90.40 ± 13.50 95.51 ± 11.99 89.33 ± 12.92
1.92 ± 1.76 3.20 ± 2.37 2.21 ± 1.44
4.88 ± 0.62 5.69 ± 0.99 5.34 ± 1.15
1.26 ± 0.30 1.36 ± 0.26 1.32 ± 0.16
SBP, systolic blood pressure; DBP, diastolic blood pressure; TG, triglyceride; TC, total cholesterol; HDL, high density lipoprotein.
were higher than those with low blood pressure for men and women. The BCd concentration of persons with highest level of blood pressure was increased by 28% compared with those with the lowest level of blood pressure.
between BCd and blood pressure. In addition, multiple linear regression analysis was also used to determine the correlation between BCd and blood pressure. But no significant correlation was found both in men and women (data not shown).
3.3.
4.
Prevalence of hypertension and BCd
The prevalence of hypertension increased with the increasing of BCd both in men and women (Table 4). Dose–response relationship was observed in women (2 = 3.90, p = 0.048) between prevalence of hypertension and BCd.
3.4.
Correlation analysis
Pearson correlation analysis was used to determine the association between blood pressure, blood lipids level and log-transformed BCd (Table 5). Significant correlations were found between SBP, DBP and BCd, age, weight, and TC in women (p < 0.05). For men, DBP was significantly correlated with weight, TG and TC. But no obvious correlation was found
Discussion
Epidemiological investigation and studies in vivo suggest that Cd may affect blood pressure (Eum et al., 2008; Donpunha et al., 2011). Some studies also show that Cd concentration of persons with hypertension is higher than that in normal persons (Gallagher and Meliker, 2010). This study demonstrates that BCd level is correlated with blood pressure, especially for female. In this study, all the people living in a Cd polluted area. But the BCd levels were individually different. Cd absorption depends on many factors, such as age, gender and nutritional status. Cd body burden increases with age and women have been shown to have higher blood levels of cadmium than men, which was consistent with the data in this study. In addition,
Table 3 – Blood cadmium/blood lipid in various blood pressure groups. SBP
n
BCda
TG
TC
HDL
Women
<140 140–160 >160
42 50 18
3.77 3.60 4.84
1.74 ± 1.03 2.02 ± 1.55 2.03 ± 1.17
5.38 ± 1.10 5.48 ± 1.09 5.66 ± 1.31
1.33 ± 0.22 1.32 ± 0.19 1.28 ± 0.26
Men
<140 140–160 >160
24 26 21
2.95 3.35 3.77
1.92 ± 1.17 2.83 ± 2.01 3.21 ± 2.69
5.12 ± 0.81 5.21 ± 0.98 6.02 ± 1.05
1.32 ± 0.24 1.27 ± 0.24 1.41 ± 0.26
SBP, systolic blood pressure; TG, triglyceride; TC, total cholesterol; HDL, high density lipoprotein. Geometric mean.
a
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e n v i r o n m e n t a l t o x i c o l o g y a n d p h a r m a c o l o g y 3 6 ( 2 0 1 3 ) 595–599
Table 4 – Prevalence of hypertension and cadmium in blood. BCd (g/L)
<2 2–5 >5 2 p a b
Women
Men
Hypertensiona (+/−)
Hypertensiona (+/−)
Hypertensiona (+/−)
Hypertensionb (+/−)
1/10 7/55 10/27 3.90 0.048
1/10 14/48 13/24 3.60 0.057
2/13 13/22 6/15 0.66 0.42
3/12 17/18 7/14 0.35 0.56
Hypertension defined by SBP. Hypertension defined by DBP.
Table 5 – Correlation analysis for different variables in women and men. Age
Women
Men
LogBCd Height Weight SBP DBP TG TC HDL LgBCd Height Weight SBP DBP TG TC HDL
0.127 −0.429** 0.011 0.514† 0.234* 0.257** 0.248** 0.097
Log BCd
Height
Weight
SBP
DBP
TG
TC
−0.232* −0.199* 0.195* 0.296* 0.146 0.252** −0.100
0.400† −0.136 0.003 −0.088 −0.155 −0.054
0.195* 0.248** 0.132 −0.087 −0.145
0.790** 0.225* 0.133 −0.082
0.046 0.129 −0.008
0.272** 0.008
−0.060
−0.038 −0.187 0.106 −0.108 0.046 0.121 0.0046
0.631** −0.179 −0.104 0.184 −0.338** −0.038
0.158 0.262* 0.361** −0.007 0.098
0.836** 0.324** 0.395** 0.147
0.321** 0.042
−0.033
*
0.258 −0.175 −0.392** 0.141 −0.178 −0.078 −0.131 0.102
0.244* 0.317** 0.101
SBP, systolic blood pressure; DBP, diastolic blood pressure; TG, triglyceride; TC, total cholesterol; HDL, high density lipoprotein. p < 0.05. ∗∗ p < 0.01. ∗
Cd absorption is also related with calcium or zinc status and intakes level of rice. BCd is one of important biomarkers for Cd exposure. BCd reflects internal Cd level, particularly in long term low level exposure. In this study, we found that SBP, DBP and prevalence of hypertension increased with the increasing of BCd, especially for women. Our study is consistent with previous studies (Tellez-plaza et al., 2008; Swaddiwudhipong et al., 2010). However, Lee et al. (2011) reported that the significant association between BCd and blood pressure was only found in men, but not in women. But in this study, the association was only found in women. We speculated the reason was that BCd level was different between different populations. In Lee’s study, the BCd of women was lower than that in men, but the situation was opposite in this study. Interestingly, we also observed that the blood lipids (TG and TC) levels increased with increasing of BCd. However, few studies mention the effects of Cd on blood lipids level. Larregle et al. (2008) indicated that Cd exposure could significantly increase TG and TC level in rats, but Cd had little effects on HDL. Recently, Tellez-Plaza et al. (2012) revealed that TC level was positively correlated with BCd in a population study. Our present study is consistent with those studies. It has been shown that lipids level is associated with blood pressure. Thus, we speculated that effects of Cd on blood pressure
may be related with its effects on lipids. In addition, we speculated that Cd may interfere with lipids metabolism. But further studies are needed before coming to a conclusion. The mechanism of Cd effects on blood pressure is not completely understood. But several models have been suggested. It has been suggested that Cd may damage vascular endothelial cells and smooth muscle cells through reactive oxidative stress and lipid peroxidation injury (Diarmid et al., 1997; Schutte et al., 2008). Cd could deposit in vascular wall (Schutte et al., 2008). Thus, it is probable that Cd could act directly on vascular wall and induce damage. In addition, Cd could disturb trace elements metabolism which is related with blood pressure (Saltman, 1983; Noël et al., 2004). Moreover, according to this study and study of Larregle et al. (2008), we speculated that Cd effects on blood pressure may be associated with its effects on lipids metabolism. In conclusion, this study indicated that BCd level was associated with blood pressure and blood lipids level, especially for women. But, because many factors are associated with blood pressure and blood lipids, further studies are needed.
Conflicts of interest statement The authors declare that there are no conflicts of interest.
e n v i r o n m e n t a l t o x i c o l o g y a n d p h a r m a c o l o g y 3 6 ( 2 0 1 3 ) 595–599
Acknowledgment This study was supported by the EU through its Sixth Framework Program for RTD (FOOD-CT-2006-016253) PHIME (Public Health Impact of long-term, low-level Mixed Element exposure in susceptible population strata) and National Natural Science Foundation of China (81102148).
references
Beevers, D.G., Campbell, B.C., Goldberg, A., Moore, M.R., Hawthorn, V.M., 1976. Blood-cadmium in hypertensive and normotnsives. Lancet 2, 1222–1224. Caciari, T., Sancini, A., Tomei, F., Antetomaso, L., Tomei, G., Scala, B., Sinibaldi, F., Di Pastena, C., Andreozzi, G., Nardone, N., Schifano, M.P., Corbosiero, P., Capozzella, A., De Sio, S., Ciarrocca, M., 2012. Cadmium blood/urine levels and blood pressure in workers occupationally exposed to urban stressor. Ann. Ig. 24, 417–428. Diarmid, M.A., Freeman, C.S., Grossman, E.A., Mortonik, J., 1997. Follow up of biologic monitoring results in cadmium workers removed from exposure. Am. J. Ind. Med. 32, 261–267. Donpunha, W., Kukongviriyapan, U., Sompamit, K., Pakdeechote, P., Kukongviriyapan, V., Pannangpetch, P., 2011. Protective effect of ascorbic acid on cadmium-induced hypertension and vascular dysfunction in mice. Biometals 24, 101–115. Eum, K.D., Lee, M.S., Paek, D., 2008. Cadmium in blood and hypertension. Sci. Total Environ. 407, 147–153. Everett, C.J., Frithsen, I.L., 2008. Association of urinary cadmium and myocardial infarction. Environ. Res. 206, 284–286. Gallagher, C.M., Meliker, J.R., 2010. Blood and urine cadmium, blood pressure, and hypertension: a systematic review and meta-analysis. Environ. Health Perspect. 118, 1676–1684. Jarup, L., 2003. Hazards of heavy metal contamination. Br. Med. Bull. 68, 167–182. Jin, T., Nordberg, G., Wu, X., Ye, T., Kong, Q., Wang, Z., Zhuang, F., Cai, S., 1998. Urinary N-acetyl--d-glucosaminidase isoenzymes as biomarker of renal dysfunction caused by cadmium in a general population. Environ. Res. A 81, 167–173. Larregle, E.V., Varas, S.M., Oliveros, L.B., Martinez, L.D., Antón, R., Marchevsky, E., Giménez, M.S., 2008. Lipid metabolism in liver of rat exposed to cadmium. Food Chem. Toxicol. 46, 1786–1792. Lee, M.S., Park, S.K., Hu, H., Lee, S., 2011. Cadmium exposure and cardiovascular disease in the 2005 Korea National Health
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and Nutrition Examination Survey. Environ. Res. 111, 171–176. Mordukhovich, I., Wright, R.O., Hu, H., Amarasiriwardena, C., Baccarelli, A., Litonjua, A., Sparrow, D., Vokonas, P., Schwartz, J., 2012. Associations of toenail arsenic, cadmium, mercury, manganese, and lead with blood pressure in the normative aging study. Environ. Health Perspect. 120, 98–104. Nordberg, G.F., 1996. Current issues in low-dose cadmium toxicology: nephrotoxicity and carcinogenicity. Environ. Sci. 4, 133–147. Noël, L., Guérin, T., Kolf-clauw, M., 2004. Subchronic dietary exposure of rats to cadmium alters the metabolism of metals essential to bone health. Food Chem. Toxicol. 42, 1203–1210. Perry Jr., H.M., Erlanger, M.W., Perry, E.F., 1977. Elevated systolic pressure following chronic low-level cadmium feeding. Am. J. Physiol. 132, h114–h121. Peters, J.L., Perlstein, T.S., Perry, M.J., McNeely, E., Wenve, J., 2010. Cadmium exposure in association with history of stroke and heart failure. Environ. Res. 110, 199–206. Saltman, P., 1983. Trace elements and blood pressure. Ann. Intern. Med. 98, 823–827. Schutte, R., Nawrot, T., Richart, T., Thijs, L., Roels, H.A., Van Bortel, L.M., Struijker-Boudier, H., Staessen, J.A., 2008. Arterial structure and function and environmental exposure to cadmium. Occup. Environ. Med. 65, 412–419. Staessen, J., Bulpitt, C.J., Roels, H., Bernard, A., Fagard, R., Joossens, J.V., Lauwerys, R., Lijnen, P., Amery, A., 1984. Urinary cadmium and lead concentrations and their relation to blood pressure in a population with low exposure. Br. J. Int. Med. 41, 241–248. Swaddiwudhipong, W., Mahasakpan, P., Limpatanachote, P., Krintratun, S., 2010. Correlations of urinary cadmium with hypertension and diabetes in persons living in cadmium-contaminated villages in northwestern Thailand: a population study. Environ. Res. 110, 612–616. Tellez-plaza, M., Navas-acien, A., Crainiceanu, C.M., Guallar, E., 2008. Cadmium exposure and hypertension in the 1999–2004 National Health and Nutrition Examination Survey (NHANES). Environ. Health Perspect. 116, 51–56. 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. Wang, H., Zhu, G., Shi, Y., Weng, S., Jin, T., Kong, Q., Nordberg, G.F., 2003. Influence of environmental cadmium exposure on forearm bone density. J. Bone Miner. Res. 18, 553–560. World Health Organization, 1992. Cadmium. Environ Health Criteria Document. World Health Organization 134, 146–151.
Available online at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/etap
The association between blood pressure and blood cadmium in a Chinese population living in cadmium polluted area Xiao Chen a,b , Guoying Zhu b , Lijian Lei c , Taiyi Jin b,∗ a b c
Department of Radiology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China Institute of Radiation Medicine, Fudan University, Shanghai 200032, China School of Public Health, Fudan University, Shanghai 200032, China
a r t i c l e
i n f o
a b s t r a c t
Article history:
Cadmium exposure may be associated with high risk of hypertension. But inconsistent
Received 25 February 2013
results have been reported. In this study, the association of blood pressure (BP) with blood
Received in revised form
cadmium (BCd) and the possible influencing factors were investigated. A total of 181 per-
10 June 2013
sons (71 men and 110 women) living near a cadmium smelter participated in this study.
Accepted 15 June 2013
The participants completed a questionnaire and BP, BCd and related biochemical indicators
Available online 24 June 2013
were measured. The geometric mean of BCd was 3.84 g/L and 3.32 g/L for women and men. The systolic blood pressure (SBP) and diastolic blood pressure both increased with the
Keywords:
increasing of BCd. The BP in women was positively correlated with BCd (p < 0.05). The BCd
Cadmium
level of participants with hypertension was obvious higher (+28%) than those with normal
Blood pressure
BP. The prevalence of hypertension was increased with the increasing of BCd, in particular
Blood lipid
to women (2 = 3.896, p = 0.048). Cadmium level in blood was associated with elevation in blood pressure, especially for women. © 2013 Elsevier B.V. All rights reserved.
1.
Introduction
Cadmium (Cd) is a hazardous heavy metal that is widely distributed in the environment. It could accumulate in food, such as rice and vegetables. Food is one of major environmental source of Cd exposure for non-smoking population (Jarup, 2003). Long-term low level of oral Cd exposure may cause chronic damage to human body. The kidney, liver, bone, and cardiovascular systems are the most important organs for Cd toxicity (World Health Organization, 1992). An important toxicological feature of Cd is its long biological half-time (10–30 years) in humans (Nordberg, 1996).
∗
It has been shown that Cd exposure may be associated with stroke, heart failure and myocardial infarction (Everett and Frithsen, 2008; Peters et al., 2010; Tellez-Plaza et al., 2012). Studies in vivo have indicated that long-term high level of Cd exposure could induce elevation of blood pressure (Perry Jr. et al., 1977). Epidemiological studies also suggest that Cd exposure is correlated with the elevation of blood pressure (Tellez-plaza et al., 2008; Eum et al., 2008; Caciari et al., 2012). However, studies also demonstrate that there are no (Beevers et al., 1976; Swaddiwudhipong et al., 2010; Mordukhovich et al., 2012) or even a negative association (Staessen et al., 1984) between blood pressure and Cd exposure. In addition, Lee et al. (2011) reported that the association of Cd and
Corresponding author at: School of Public Health, Fudan University, 200032 Shanghai, China. Tel.: +86 21 64438121; fax: +86 21 64049847. E-mail addresses: chx [email protected], [email protected] (T. Jin). 1382-6689/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.etap.2013.06.006
596
e n v i r o n m e n t a l t o x i c o l o g y a n d p h a r m a c o l o g y 3 6 ( 2 0 1 3 ) 595–599
hypertension was only found in male and no association was found in female. Blood pressure is related with blood lipids level. It has been indicated that Cd may disturb lipids metabolism in vivo (Larregle et al., 2008). But we do know whether the hypertension caused by Cd is related with blood lipids level. This study tries to observe the association between blood Cd and blood pressure in a Chinese population living in a Cd polluted area. In addition, we also observe the effects of Cd exposure on blood lipids level.
2.3.
The blood pressure was measured twice on right wrist using electronic sphygmomanometer (Omron, Dalian, China) in a sitting position. Because wrist blood pressure measured by the electronic sphygmomanometer was higher than arm blood pressure measured by mercury sphygmomanometer. In this study, hypertension was regarded as diastolic pressure >95 mm Hg and or/systolic pressure >160 mm Hg or receipt of current antihypertensive treatment.
2.4.
2.
Materials and method
2.1.
Area and study population
Total 181 persons aged 40 years and older, living in a Cdcontaminated area, were recruited in this study. A smelter was located in this area and industrial wastewater was regularly discharged into the river near the factory. The concentrations of metals (Cd, Lead, and Copper) in the wastewater exceeded the levels of Chinese hygiene standards. The residents living in the polluted areas used the polluted river for irrigation from 1961 to 1995. The Cd concentration in rice was about 3.7 mg/kg and the main staple food in these areas was the rice that they produced from these fields. From 1996 onward, however, the residents stopped producing rice in these fields and began eating commercially available rice from other (non-polluted) areas (Cd in rice: 0.03 mg/kg). More detailed information has been provided previously (Wang et al., 2003). The participants in the study gave their informed consent and completed a questionnaire including information on medical and drug history, cigarette smoking, alcohol consumption and medical history of hypertension. Height and weight data were obtained to calculate body mass index (kg/m2 ). Samples of venous blood were collected from each participant for determination of Cd concentration and biochemical indicators. During this study, Declaration of Helsinki was followed. This study was carried out with the permission of the Ethics Committees of Fudan University.
2.2.
Blood pressure measurement
Lipids level measurements
Fasting blood triglyceride (TG), total cholesterol (TC) and high density lipoprotein (HDL) level were measured by automatic biochemical analyzer (Hitach7150, Japan).
2.5.
Statistical analysis
Database management and analysis were performed using SPSS11.5 (SPSS Inc, Chicago, IL, USA) and EPI INFO (Version 3.5.1, Centers for Disease Control and Prevention, Atlanta, GA, USA). Arithmetic means were compared by using one wayANOVA and Pearson correlation was applied to analyze the correlation of BP with BCd (log-transformed), height, weight and other biochemical indicators. The data were expressed as mean ± SD. The criterion significance level was set at p < 0.05.
3.
Results
3.1.
3.1. Characteristics of study population
The general characteristics of study population, the BCd concentration and lipids level were shown in Table 1. 61% of the participants were female. There were significant differences between men and women in height, weight and tobacco smoking (p < 0.05). The concentration of BCd in women was slightly higher than that in men. The systolic blood pressure (SBP) and diastolic blood pressure (DBP) in men were higher than those in women, but no significant differences were found. No obvious differences were found in blood lipids level between men and women.
Exposure assessment 3.2.
Collection of samples followed a strict protocol. Cd was measured as already described (Jin et al., 1998). Briefly, blood samples were collected in heparin tubes and stored frozen (−20 ◦ C) until analyzed. Cd content in blood (BCd) was measured by graphite-furnace atomic absorption spectrometry (GF-AAS, ShimadzuAA-670, Kyoto, Japan). Between and within bottle homogeneity testing was below 6% and 7%. For quality control, reference material (lyophilized whole human blood) with two certified concentration (9.6 ± 1.7 g/kg and 3.3 ± 0.9 g/kg) were analyzed. The obtained Cd concentrations were 11.1 ± 0.2 g/kg and 4.8 ± 0.3 g/kg. The detection limit of Cd in blood using this method was 0.05 g/L. BCd was used as measures of the exposure. BCd reflects Cd body burden (Diarmid et al., 1997), particularly in long term low level of exposure and after cessation of exposure.
BCd and blood pressure
The blood pressure, TG and TC were increased with the increasing of BCd in women (Table 2). Compared with the subjects with the lowest level of BCd, the SBP and DBP in the subjects with the highest level of BCd were increased by 8% and 4%, respectively, after adjusted for age and BMI. But no significant differences were found. Meanwhile, TG and TC increased by 30% and 17% in the people with the highest level of BCd compared with those with the lowest level of BCd. For men, the blood pressure, TG and TC level were higher in middle BCd group compared with other BCd group, but there was no significant difference. Consequently, men and women were divided into three groups according to the level of blood pressure (Table 3). The BCd, TG and TC of those persons with high blood pressure
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Table 1 – Characteristics of study population.
Age (years) Body weight (kg) Height (cm) Triglyceride (mmol/L) Cholesterol (mmol/L) High density lipoprotein (mmol/L) Systolic blood pressure (mm Hg) Diastolic blood pressure (mm Hg) BCda (g/L) Smoking ∗ a
Total (n = 181)
Women (n = 110)
Men (n = 71)
58.2 ± 10.8 62.67 ± 10.68 159.59 ± 7.48 2.20 ± 1.68 5.45 ± 1.08 1.32 ± 0.23 145.97 ± 18.30 90.04 ± 11.97 3.63 38 (21%)
57.4 ± 9.2 58.57 ± 8.51 155.51 ± 5.27 1.92 ± 1.31 5.47 ± 1.12 1.32 ± 0.21 143.41 ± 7.36 88.37 ± 11.21 3.84 0
59.8 ± 11.8 69.02 ± 10.64* 165.91 ± 5.84* 2.64 ± 2.06 5.41 ± 1.01 1.33 ± 0.25 149.97 ± 9.11 92.64 ± 12.71 3.32 38 (54%)*
P < 0.05, compared with women. Geometric mean.
Table 2 – Blood cadmium and blood pressure/blood lipid in women and men. BCd (g/L)
n
Age
SBP
DBP
TG
TC
HDL
Women
<2 2–5 >5
11 62 37
54.60 ± 6.48 56.45 ± 9.23 59.97 ± 9.28
138.91 ± 13.44 141.84 ± 16.83 147.35 ± 18.88
84.91 ± 7.80 87.18 ± 9.38 90.59 ± 13.10
1.73 ± 0.73 1.83 ± 1.00 2.28 ± 1.82
4.85 ± 0.74 5.35 ± 0.90 5.64 ± 1.42
1.30 ± 0.12 1.35 ± 0.22 1.31 ± 0.22
Men
<2 2–5 >5
15 35 21
58.33 ± 11.79 58.05 ± 13.61 58.33 ± 12.89
143.2 ± 17.00 154.0 ± 18.17 148.10 ± 21.18
90.40 ± 13.50 95.51 ± 11.99 89.33 ± 12.92
1.92 ± 1.76 3.20 ± 2.37 2.21 ± 1.44
4.88 ± 0.62 5.69 ± 0.99 5.34 ± 1.15
1.26 ± 0.30 1.36 ± 0.26 1.32 ± 0.16
SBP, systolic blood pressure; DBP, diastolic blood pressure; TG, triglyceride; TC, total cholesterol; HDL, high density lipoprotein.
were higher than those with low blood pressure for men and women. The BCd concentration of persons with highest level of blood pressure was increased by 28% compared with those with the lowest level of blood pressure.
between BCd and blood pressure. In addition, multiple linear regression analysis was also used to determine the correlation between BCd and blood pressure. But no significant correlation was found both in men and women (data not shown).
3.3.
4.
Prevalence of hypertension and BCd
The prevalence of hypertension increased with the increasing of BCd both in men and women (Table 4). Dose–response relationship was observed in women (2 = 3.90, p = 0.048) between prevalence of hypertension and BCd.
3.4.
Correlation analysis
Pearson correlation analysis was used to determine the association between blood pressure, blood lipids level and log-transformed BCd (Table 5). Significant correlations were found between SBP, DBP and BCd, age, weight, and TC in women (p < 0.05). For men, DBP was significantly correlated with weight, TG and TC. But no obvious correlation was found
Discussion
Epidemiological investigation and studies in vivo suggest that Cd may affect blood pressure (Eum et al., 2008; Donpunha et al., 2011). Some studies also show that Cd concentration of persons with hypertension is higher than that in normal persons (Gallagher and Meliker, 2010). This study demonstrates that BCd level is correlated with blood pressure, especially for female. In this study, all the people living in a Cd polluted area. But the BCd levels were individually different. Cd absorption depends on many factors, such as age, gender and nutritional status. Cd body burden increases with age and women have been shown to have higher blood levels of cadmium than men, which was consistent with the data in this study. In addition,
Table 3 – Blood cadmium/blood lipid in various blood pressure groups. SBP
n
BCda
TG
TC
HDL
Women
<140 140–160 >160
42 50 18
3.77 3.60 4.84
1.74 ± 1.03 2.02 ± 1.55 2.03 ± 1.17
5.38 ± 1.10 5.48 ± 1.09 5.66 ± 1.31
1.33 ± 0.22 1.32 ± 0.19 1.28 ± 0.26
Men
<140 140–160 >160
24 26 21
2.95 3.35 3.77
1.92 ± 1.17 2.83 ± 2.01 3.21 ± 2.69
5.12 ± 0.81 5.21 ± 0.98 6.02 ± 1.05
1.32 ± 0.24 1.27 ± 0.24 1.41 ± 0.26
SBP, systolic blood pressure; TG, triglyceride; TC, total cholesterol; HDL, high density lipoprotein. Geometric mean.
a
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Table 4 – Prevalence of hypertension and cadmium in blood. BCd (g/L)
<2 2–5 >5 2 p a b
Women
Men
Hypertensiona (+/−)
Hypertensiona (+/−)
Hypertensiona (+/−)
Hypertensionb (+/−)
1/10 7/55 10/27 3.90 0.048
1/10 14/48 13/24 3.60 0.057
2/13 13/22 6/15 0.66 0.42
3/12 17/18 7/14 0.35 0.56
Hypertension defined by SBP. Hypertension defined by DBP.
Table 5 – Correlation analysis for different variables in women and men. Age
Women
Men
LogBCd Height Weight SBP DBP TG TC HDL LgBCd Height Weight SBP DBP TG TC HDL
0.127 −0.429** 0.011 0.514† 0.234* 0.257** 0.248** 0.097
Log BCd
Height
Weight
SBP
DBP
TG
TC
−0.232* −0.199* 0.195* 0.296* 0.146 0.252** −0.100
0.400† −0.136 0.003 −0.088 −0.155 −0.054
0.195* 0.248** 0.132 −0.087 −0.145
0.790** 0.225* 0.133 −0.082
0.046 0.129 −0.008
0.272** 0.008
−0.060
−0.038 −0.187 0.106 −0.108 0.046 0.121 0.0046
0.631** −0.179 −0.104 0.184 −0.338** −0.038
0.158 0.262* 0.361** −0.007 0.098
0.836** 0.324** 0.395** 0.147
0.321** 0.042
−0.033
*
0.258 −0.175 −0.392** 0.141 −0.178 −0.078 −0.131 0.102
0.244* 0.317** 0.101
SBP, systolic blood pressure; DBP, diastolic blood pressure; TG, triglyceride; TC, total cholesterol; HDL, high density lipoprotein. p < 0.05. ∗∗ p < 0.01. ∗
Cd absorption is also related with calcium or zinc status and intakes level of rice. BCd is one of important biomarkers for Cd exposure. BCd reflects internal Cd level, particularly in long term low level exposure. In this study, we found that SBP, DBP and prevalence of hypertension increased with the increasing of BCd, especially for women. Our study is consistent with previous studies (Tellez-plaza et al., 2008; Swaddiwudhipong et al., 2010). However, Lee et al. (2011) reported that the significant association between BCd and blood pressure was only found in men, but not in women. But in this study, the association was only found in women. We speculated the reason was that BCd level was different between different populations. In Lee’s study, the BCd of women was lower than that in men, but the situation was opposite in this study. Interestingly, we also observed that the blood lipids (TG and TC) levels increased with increasing of BCd. However, few studies mention the effects of Cd on blood lipids level. Larregle et al. (2008) indicated that Cd exposure could significantly increase TG and TC level in rats, but Cd had little effects on HDL. Recently, Tellez-Plaza et al. (2012) revealed that TC level was positively correlated with BCd in a population study. Our present study is consistent with those studies. It has been shown that lipids level is associated with blood pressure. Thus, we speculated that effects of Cd on blood pressure
may be related with its effects on lipids. In addition, we speculated that Cd may interfere with lipids metabolism. But further studies are needed before coming to a conclusion. The mechanism of Cd effects on blood pressure is not completely understood. But several models have been suggested. It has been suggested that Cd may damage vascular endothelial cells and smooth muscle cells through reactive oxidative stress and lipid peroxidation injury (Diarmid et al., 1997; Schutte et al., 2008). Cd could deposit in vascular wall (Schutte et al., 2008). Thus, it is probable that Cd could act directly on vascular wall and induce damage. In addition, Cd could disturb trace elements metabolism which is related with blood pressure (Saltman, 1983; Noël et al., 2004). Moreover, according to this study and study of Larregle et al. (2008), we speculated that Cd effects on blood pressure may be associated with its effects on lipids metabolism. In conclusion, this study indicated that BCd level was associated with blood pressure and blood lipids level, especially for women. But, because many factors are associated with blood pressure and blood lipids, further studies are needed.
Conflicts of interest statement The authors declare that there are no conflicts of interest.
e n v i r o n m e n t a l t o x i c o l o g y a n d p h a r m a c o l o g y 3 6 ( 2 0 1 3 ) 595–599
Acknowledgment This study was supported by the EU through its Sixth Framework Program for RTD (FOOD-CT-2006-016253) PHIME (Public Health Impact of long-term, low-level Mixed Element exposure in susceptible population strata) and National Natural Science Foundation of China (81102148).
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