The association of lead exposure with blood pressure and hypertension: a mediation analyses of estimated glomerular filtration rate

The link between lead and blood pressure was debatable, and whether it was mediated by renal function was unknown. The purpose was to investigate the relationship between blood lead concentrations and blood pressure and hypertension, as well as the mediating role of estimated glomerular filtration rate (eGFR) in this relationship. Participants aged 18 were recruited from the National Health and Nutrition Examination Survey (1999–2014) and provided with lead and blood pressure data. Multivariate linear and logistic regression, stratification, interaction tests, and a restricted cubic spline curve were used to assess the association of blood lead with systolic/diastolic blood pressure (SBP/DBP) and hypertension, and mediation effect analysis was used to investigate the role of eGFR in this relationship. A total of 20,073 subjects were enrolled, and among them, 9837 (49.01%) were male and 7800 (38.86%) were hypertensive patients. Multivariate linear and logistic regression analysis showed that blood lead levels were significantly associated with SBP ( β = 3.14, 95%CI: 2.03, 4.25; P < 0.001), DBP ( β = 3.50, 95%CI: 2.69, 4.30; P < 0.001), and hypertension (OR = 1.29, 95%CI: 1.09, 1.52; P = 0.0026). In comparison to the lowest blood lead quartile, the highest lead group was significantly associated with SBP (= 2.55, 95%CI: 1.66, 3.44; P = 0.0001), DBP (= 2.60, 95%CI: 1.95, 3.24; P = 0.0001), and hypertension (OR = 1.26, 95%CI: 1.10, 1.45; P = 0.0007). Mediation analysis showed that the proportion of blood lead mediated for SBP, DBP, and hypertension was 3.56% (95%CI: 0.42%, 7.96%; P = 0.0320), 6.21% (95%CI: 4.02%, 9.32%; P < 0.0001), and 17.39% (95%CI: 9.34%, 42.71%; P < 0.0001), respectively. Adjusted restricted cubic spline curves presented a non-linear correlation of blood lead levels with DBP (P-non-linearity < 0.001), linear with SBP (P-non-linearity = 0.203), and hypertension (P-non-linearity = 0.763). Our findings demonstrated that blood lead levels were non-linear with DBP, but linear with SBP and hypertension, and this relationship was mediated by eGFR.