Aims : Heavy metals (HM) are combustion-related environmental factors predisposing to cardiovascular (CVD), autoimmune and liver diseases, even below regulatory concentrations. Pro-atherogenic and pro-steatotic auto-antibodies against apolipoprotein A1 (AAA1) are prevalent in the general population for unclear reasons. We explored a putative interplay between HM exposure, AAA1, CVD risk factors and a non-alcoholic fatty liver disease (NAFLD) risk score, using a geospatial clustering approach at the general population level.

Methods : Getis-Ord, Moran I2 clustering and geographically weighted regression (GWR) geosptatial analyses were carried out on 6361 individuals recruited in the CoLaus/PsyCoLaus general population cohort. Geospatial dependences between serum AAA1, urinary HM (cadmium, arsenic, cobalt) concentrations, SCORE2 CVD risk, and fatty liver index (FLI) were assessed.

Results : Cadmium and cobalt were found to be associated with higher SCORE2 risk (p<0.04). AAA1 were associated with higher cadmium, cobalt, and cigarette consumption, independently of SCORE2 (p<0.04). AAA1 hotspots overlapped significantly with those of cadmium and FLI, independently of SCORE2. According to GWR, correlations between cadmium and AAA1 were the highest in railways proximity regions, increasing up to 10-fold compared to global associations. AAA1 were not associated with other HM.

Conclusions : These geospatial footprints highlight independent associations between Cadmium, AAA1, and NAFLD risk score in the general population. We hypothesize that environmental cadmium exposure may facilitate the occurrence of AAA1 in humans. Ongoing experimental studies will confirm/refute a possible causal link. Whether AAA1 could represent an early biological signature of cadmium exposure and subsequent health hazards remains to be shown.