Cadmium exposure and risk of hypertension: A systematic review and dose-response meta-analysis

BACKGROUND: Exposure to environmental toxic metals represents a significant global public health concern. Many studies have reported that cadmium (Cd) exposure increases the risk of hypertension. Since the shape of such relation has not been well characterized, we assessed it by performing a systematic review and dose-response meta-analysis of human studies. METHODS: We searched the literature through September 5, 2024 to identify papers related to Cd, hypertension, and blood pressure. Inclusion criteria were: observational design, adult population, assessment of exposure using Cd biomarkers, and availability of exposure category-specific risk estimates for hypertension. We performed a dose-response meta-analysis of the results from included studies. RESULTS: Of the 18 studies published between 2006 and 2024, most had a cross-sectional design. Cd was measured in whole blood and/or urine in almost all studies, whereas only two studies measured Cd in serum. The dose-response meta-analysis indicated an almost linear relation between urinary Cd concentrations and hypertension risk with RR = 1.18, 95% CI 1.02-1.37 at 2.0 μg/g creatinine compared with no exposure. In contrast, the association between blood Cd concentrations and hypertension risk was non-linear: there was a steep monotonic increase in risk for Cd concentrations below 2 μg/L, reaching a RR of 1.48 (95% CI 1.17-1.86) at 2.0 μg/L, after which a plateau seemed reached. We found similar trends when restricting to studies of Asian population, while when considering North American studies, hypertension risk increased above 1.0 μg/g creatinine. CONCLUSIONS: In this dose-response meta-analysis, risk of hypertension showed a non-linear positive association with blood Cd concentrations and a linear positive association with urinary Cd concentrations. Inconsistency in the shape of associations could relate to the different timing of exposure assessed by the biomarkers or the alteration Cd excretion at increasing exposure levels. Mitigation of Cd exposure is confirmed as a public health priority for chronic disease prevention.