Air pollution, coronary artery disease, and cardiovascular events: Insights
from the PROMISE trial
Marcel C. Langenbacha,b,c, Thomas Mayrhofera,d,e, Isabel L. Langenbacha,b, Michael T. Lua
Julia Karadya, David Maintz b, Shady Abohashema, Ahmed Tawakola, Neha J. Pagidipati f,g
Svati H. Shah f,g, Maros Ferencik h, Alison Motsinger-Reif i, Pamela S. Douglas f, Borek Foldynaa,
a Cardiovascular Imaging Research Center, Massachusetts General Hospital, Harvard Medical School, 165 Cambridge St, Suite 400, Boston, MA, 02114, USA
b Institute for Diagnostic and Interventional Radiology, University Hospital Cologne, Kerpener Str 62, 50937, Cologne, Germany
c Department of Diagnostic and Interventional Radiology, University Hospital Augsburg, Stenglinstr. 2, 86156, Augsburg, Germany
d Center for Preventive Medicine and Digital Health, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany
e School of Business Studies, Stralsund University of Applied Sciences, Zur Schwedenschanze 15, 18435, Stralsund, Germany
f Duke Clinical Research Institute, Duke University School of Medicine, 300 W. Morgan St, Durham, NC, 27701, USA
g Division of Cardiology, Department of Medicine, Duke University Medical Center, 10 Duke Medicine Cir, Durham, NC, 27710, USA
h Knight Cardiovascular Institute, Oregon Health & Science University, 15700 S.W. Greystone Ct, Beaverton, OR, 97006, USA
i Biostatistics and Computational Biology Branch, Division of Intramural Research, National Institute of Environmental Health Sciences, 111 Tw Alexander Dr, Research
Triangle Park, NC, 27709, USA
A B S T R A C T
Keywords:
Computed tomography
Socioeconomic determinants of health
Air pollution
Coronary artery disease
Adverse cardiac events
Background: Air pollution is associated with mortality and major adverse cardiovascular events (MACE) in the
general population. However, little is known about the relationship between air pollution and coronary artery
disease (CAD) and how this relates to MACE.
Methods: This study utilized data from the computed tomography (CT) arm of the PROMISE trial investigating
symptomatic individuals with suspected CAD. We linked levels of air pollutants (PM2⋅5, PM10, NO2, and ozone) at
U.S. zip codes of residence CT-derived CAD and adjudicated MACE (all-cause death, myocardial infarction, and
hospitalization for unstable angina). Multivariable analyses were adjusted for the ASCVD risk score and socio-
economic determinants of health. Mediation analyses were used to test putative pathways.
Results: In 4343 individuals (48 % males; age: 61 8 years), elevated exposures to PM2.5 ( 9.4 μg/m3) and NO2
( 5.3 ppb) were independently associated with obstructive CAD (aOR¼ 1.23, 95%CI: 1.03–1.48, p¼ 0.024; aOR
¼ 1.56, 95%CI: 1.02–2.40, p¼ 0.042), while there were no signi cant associations with PM10 ( 15 μg/m3) or
ozone ( 51 ppb). Increased PM2.5, PM10 and ozone were independently associated with MACE (aHR¼ 1.56, 95%
CI: 1.12–2.18, p¼ 0.008; aHR¼ 2.09, 95%CI: 1.18–3.70, p¼ 0.011, aHR¼ 1.96, 95%CI: 1.20–3.21, p¼ 0.008).
In the mediation analysis, obstructive CAD accounted for 9 % of the total effect (p¼ 0.012) between PM2.5 and
MACE.
Conclusion: Exposure to air pollution, particularly PM2.5, was independently associated with obstructive CAD and
MACE, with obstructive CAD mediating a small but signi cant portion of the association between air pollution
and MACE.