Long‐term exposure to fine particulate matter constituents, genetic susceptibility, and incident heart failure among 411 807 adults

Aims Long‐term fine particulate matter (PM 2.5 ) exposure has been linked to incident heart failure (HF), but the impacts of its constituents remain unknown. We aimed to investigate the associations of PM 2.5 constituents with incident HF, and further evaluate the modification effects of genetic susceptibility. Methods and results PM 2.5 and its constituents, including elemental carbon (EC), organic matter (OM), ammonium (NH 4 + ), nitrate (NO 3 − ), and sulfate (SO 4 2− ), were estimated using the European Monitoring and Evaluation Programme model applied to the UK (EMEP4UK) driven by Weather and Research Forecast model meteorology. A polygenic risk score (PRS) was calculated to represent genetic susceptibility to HF. We employed Cox models to evaluate the associations of PM 2.5 constituents with incident HF. Quantile‐based g‐computation model was used to identify the main contributor of PM 2.5 constituents. Among 411 807 individuals in the UK Biobank, 7554 participants developed HF during a median follow‐up of 12.05 years. The adjusted hazard ratios of HF for each interquartile range increase in PM 2.5 , EC, OM, NH 4 + , NO 3 − , and SO 4 2− were 1.50 (1.46–1.54), 1.31 (1.27–1.34), 1.12 (1.09–1.15), 1.42 (1.41–1.44), 1.26 (1.23–1.29), and 1.25 (1.24–1.26), respectively. EC (43%) played the most important role, followed by NH 4 + and SO 4 2− . Moreover, synergistic additive interactions accounted for 9–16% of the HF events in individuals exposed to both PM 2.5 , NH 4 + , NO 3 − , and SO 4 2− and PRS. Conclusion Long‐term exposure to PM 2.5 constituents may elevate HF risk, and EC was the major contributor. Additive effects of PM 2.5 constituents and PRS on HF risk were revealed.