Abstract Body (Do not enter title and authors here): Background: Artificial light at night (ALAN) is ubiquitous in modern cities and linked to cardiometabolic disorders, yet its independent contribution to cardiovascular disease (CVD) remains uncertain. Stress-related neural-arterial pathways link socioenvironmental stressors to CVD, but their role in the ALAN-CVD relationship is unknown.
Hypothesis : Higher residential ALAN exposure is independently associated with (1) elevated stress-related neural activity (SNA), (2) greater arterial inflammation (ArtI), and (3) higher risk of major adverse cardiovascular events (MACE), and that the ALAN–MACE link is serially mediated through the SNA→ArtI pathway.

Methods: We studied 466 adults (median age 55 y; 43 % men) who underwent clinical ¹⁸F-FDG PET/CT at Massachusetts General Hospital (2005-2008) without cancer or CVD at baseline. ALAN exposure was assigned to geocoded home addresses using the New World Atlas of Artificial Night Sky Brightness and analyzed per SD (z-score) and in quartiles. SNA was quantified on FDG PET/CT imaging as the amygdala-to-cortical activity ratio (AmygA_c). ArtI was assessed as the aortic target-to-background ratio. Traditional CVD, socio-environmental (air/noise, income, urbanicity) and medical (malignancy, psychiatric) covariates were abstracted. Multivariable linear and Cox models, Restricted Cubic Splines and serial mediation analyses were employed.

Results: During 10-year follow-up, 79 participants (17 %) experienced MACE. Each 1-SD higher ALAN independently associated with higher AmygA_c (standardized β 0.14, 95 % CI 0.01-0.27; p = 0.03*) and greater ArtI (0.09, 0.00-0.17; p = 0.04**). Splines analysis showed a nearly linear relationship (AmygA_c: p nonlinear=0.48; ArtI: p nonlinear=0.82; 1A-B). ALAN associated with 5-year (HR 1.35, 95 % CI 1.05-1.74**) and 10-year MACE (1.22, 1.01-1.50**). Kaplan–Meier showed a stepwise decrease in event-free survival across ALAN quartiles (log-rank p < 0.001; 1C). These associations persisted after further adjustment for socio-environmental factors and medical history. In mediation analysis, the indirect ALAN→SNA→ArtI→MACE path was significant (log-odds 0.015, p<.05**; 1D).

Conclusions: Higher ALAN exposure is independently, and dose-dependently, associated with greater SNA, increased ArtI, and incident MACE. These findings support a stress-mediated neural-arterial pathway linking light pollution to CVD and position ALAN as a modifiable urban exposure target for CVD prevention.