Aims: Autoantibodies against apolipoprotein A-1 (AAA1) are independent cardiovascular risk factor in the general population. Genetic factors and viral infections have been linked to AAA1 occurrence. We studied the association between environmental pollution and AAA1 response and their relationship with years of life lost or gained (YPLLG).

Methods: We conducted a cross-sectional study involving 1867 individuals recruited between 2016 and 2018 in Geneva, Switzerland, characterized for serum AAA1 levels. Exploratory and confirmatory geospatial analyses of AAA1, air pollution (NO₂ , PM₂ .₅ , PM₁₀ ), proximity to polluted sites, and YPLLG were performed. Associations with AAA1 were adjusted for premature mortality risk factors using Systemic Coronary Risk Evaluation 2 (SCORE2), while associations with YPLLG were adjusted for income, nationality, NO₂ levels, and proximity to polluted sites.

Results: Significant geographic clustering of high AAA1 serum levels (hotspots) were identified in urban areas with heavy traffic, associated with higher air pollutant levels (median NO₂ 26.90 μg/m³ in hotspots vs. 23.70 μg/m³ in non-hotspots, p < 0.001), and greater density of polluted sites (median weighted pollution score 66.8 vs. 52.1, p = 0.008). AAA1 geographic hotspots corresponded to areas showing a median reduction of four years in population life expectancy, based on mortality records (2009-2016) (p < 0.001), even after adjustments.

Conclusions: While causal inference cannot be drawn due to the cross-sectional design, AAA1 hotspots overlapped regions of higher air and soil pollution and reduced life expectancy. Determining causality and whether specific pollutants amplify the AAA1 response will be key to validate these hypothesis-generating findings.