Academic journal article Environmental Health Perspectives

Blood and Urine Cadmium, Blood Pressure, and Hypertension: A Systematic Review and Meta-Analysis

Academic journal article Environmental Health Perspectives

Blood and Urine Cadmium, Blood Pressure, and Hypertension: A Systematic Review and Meta-Analysis

Article excerpt

BACKGROUND: Cadmium exposure has been inconsistently related to blood pressure.

OBJECTIVES: We updated and reevaluated the evidence regarding the relationships of blood cadmium (BCd) and urine cadmium (UCd) with blood pressure (BP) and hypertension (HTN) in nonoccupationally exposed populations.

DATA SOURCES AND EXTRACTION: We searched PubMed and Web of Science for articles on BCd or UCd and BP or HTN in nonoccupationally exposed populations and extracted information from studies that provided sufficient data on population, smoking status, exposure, outcomes, and design.

DATA SYNTHESIS: Twelve articles met inclusion criteria: eight provided data adequate for comparison, and five reported enough data for meta-analysis. Individual studies reported significant positive associations between BCd and systolic BP (SBP) among nonsmoking women [[beta] = 3.14 mmHg per 1 [micro]g/L untransformed BCd; 95% confidence interval (CI), 0.14-6.14] and among premenopausal women ([beta] = 4.83 mmHg per 1 nmol/L log-trans formed BCd; 95% CI, 0.17-9.49), and between BCd and diastolic BP (DBP) among women ([beta] = 1.78 mmHg comparing BCd in the 90th and 10th percentiles; 95% CI, 0.64-2.92) and among premenopausal women ([beta] = 3.84 mmHg per 1 nmol/L log-transformed BCd; 95% CI, 0.86-6.82). Three meta-analyses, each of three studies, showed positive associations between BCd and SBP (p = 0.006) and DBP (p < 0.001) among women, with minimal heterogeneity ([I.sup.2] = 3%), and a significant inverse association between UCd and HTN among men and women, with substantial heterogeneity ([I.sup.2] = 80%).

CONCLUSION: Our results suggest a positive association between BCd and BP among women; the results, however, are inconclusive because of the limited number of representative population-based studies of never-smokers. Associations between UCd and HTN suggest inverse relationships, but inconsistent outcome definitions limit interpretation. We believe a longitudinal study is merited.

KEY WORDS: blood, blood pressure, cadmium, hypertension, meta-analysis, smoking, systematic review, urine. Environ Health Perspect 118:1676-1684 (2010). doi:10.1289/ehp.1002077 [Online 17 August 2010]


Hypertension (HTN) and smoking are established risk factors for cardiovascular disease (U.S. Department of Health and Human Services 2000), the leading cause of death worldwide (World Health Organization 2009). The etiology of essential HTN, however, is unknown (Carretero and Oparil 2000), but cadmium exposure has been inconsistently associated with blood pressure (BP). For example, Jarup and Akesson (2009) recently reviewed the literature on cadmium and health effects and identified single-study-reported associations between cadmium and cardiovascular effects other than HTN. More than 10 years earlier, Nakagawa and Nishijo (1996) conducted a review of cadmium exposure and HTN and found that, although general population studies had reported positive associations of blood cadmium (BCd) and urinary cadmium (UCd) with BP, inverse associations had been reported in studies of residents or workers with known environmental or occupational exposures. Nakagawa and Nishijo (1996) interpreted these differences as an effect of low versus high exposures to cadmium, identified exposure misclassification as a limitation of studies conducted before the 1970s when cadmium measurements were semiquantitative, and also noted failure to account for the influence of smoking as a concern. Smoking is associated with increased cadmium levels because cigarettes contain cadmium taken up by the tobacco plant [Agency for Toxic Substances and Disease Registry (ATSDR) 2008]. Smokers have approximately twice the cadmium body burden of nonsmokers (ATSDR 2008). In nonsmokers, however, food is the primary source of exposure (ATSDR 2008). Nakagawa and Nishijo (1996) concluded that additional studies that control for smoking are needed, and several new studies that separated smokers from nonsmokers have been published since their review. …

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