Independent association of blood cadmium with subclinical lower extremity atherosclerosis: An observational study based on dose-response analysis

Background: Atherosclerosis is an increasingly public health issue globally. Previous studies have showed a causal link between heavy metal exposure and atherosclerosis. However, the association of cadmium concentration with subclinical lower extremity atherosclerosis (SLEA) remains unclear.Aims: To investigate the association of blood cadmium with SLEA and its extent, and further analyze the potential dose-response relationship.Methods: Blood cadmium concentration was measured using inductively coupled plasma mass spectrometry. SLEA and its extent were assessed by ultrasound diagnosis system. Multivariate models were applied to evaluate the association of blood cadmium with SLEA and its extent. Restricted cubic splines were performed to explore the potential dose-response relationship.Results: This observational study consisted of 1664 participants from cardiovascular outpatient, with an average age of 62.4 years and 1218 (73.2%) men. When blood cadmium was included as a categorical variable in multivariate models, logistic regression analysis showed that high quartile in blood cadmium was an indepen-dent risk factor of SLEA (OR = 2.704, 95%CI 1.866-3.919). After log-transformed for SLEA extent parameters, linear regression analysis indicated that high quartile in blood cadmium was significantly associated with higher Crouse score (GMR = 1.21, 95%CI 1.15-1.28), plaque maximum thickness (GMR = 1.13, 95%CI 1.09-1.18) and diseased vessel count (GMR = 1.14, 95%CI 1.10-1.19), respectively. When blood cadmium was used as a continuous variable in restricted cubic splines, the dose-response relationship presented a positive progression in SLEA (P = 0.302), plaque maximum thickness (P = 0.145) and diseased vessel count (P = 0.055) apparently that did not deviate from linearity.Conclusions: Blood cadmium exhibited an independent association with SLEA, and this dose-response relationship was progressive without significant departure from linearity.