Sex-specific associations between long-term exposure to ambient air pollution and the cardiac conduction system - a longitudinal analysis of the KORA cohort

Altered cardiac electrophysiological activity may represent an important mechanism linking long-term air pollution exposure to cardiovascular disease. However, evidence on chronic exposure effects on specific ECG parameters, particularly the heart rate–corrected JT (JTc) interval as a sensitive marker of ventricular repolarization, remains limited. We investigated associations between long-term exposure to ambient air pollutants and ECG parameters of cardiac conduction and repolarization, with emphasis on sex-specific effects. We analyzed 9181 repeated 12-lead ECGs from 4143 participants in the population-based KORA S4, F4 and FF4 studies. Annual average residential exposures to nitrogen dioxide (NO 2 ), particulate matter ≤2.5 μm (PM 2.5 ), and particle number concentration (PNC; ultrafine particles ≤100 nm) were estimated using land-use regression models. Associations were assessed using generalized additive mixed models with sex interactions. Effect modification by obesity, smoking, and education was examined in sex-stratified analyses. In men, an interquartile range (IQR) increase in PNC was associated with a 0.49% (95% CI: 0.07, 0.91) higher heart rate (HR), while IQR increases in PM 2.5 and NO 2 were associated with 0.31% (95% CI: 0.10, 0.51) and 0.51% (95% CI: 0.28, 0.74) prolongations of JTc, respectively. In women, main-model estimates were less consistent; stratified analyses suggested stronger positive associations in subgroups defined by obesity, smoking history, and lower educational attainment, with the strongest effects among women with multiple susceptibility characteristics. Long-term air pollution exposure was associated with increased heart rate and prolonged JTc, supporting a role of chronic air pollution in subclinical electrophysiological changes and motivating further work to confirm vulnerable phenotypes.