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Air Pollution and Cardiovascular Health 
Dr Jeremy Langrish1 & Dr Mark Miller2 
1Clinical Lecturer & Specialty Registrar in Cardiology 
2Senior Research Fellow 
Centre for Cardiovascular Sciences 
University of Edinburgh / Edinburgh Heart Centre 
Scottish Transport Emissions Partnership. “Step 2 Conference” 
School of Informatics, Edinburgh, 18th November 2014
Air Pollution and Health
Air Pollution and Health
Air Pollution and Health
Air Pollution and Health
Air pollution today
So what is air pollution? 
Particles 
Gases 
Volatile 
Liquids 
organic species 
reactive metals
Fine and ultrafine PM 
Adsorbed chemicals 
Metals 
Nitrates / sulphates 
Organic compounds 
Carbon core
Particles & mortality
Particles & Cardiorespiratory disease 
Risk of dying from cardiorespiratory disease increased by 37% in the most polluted as compared to the least polluted city 
Risk increases by 6% for each increase in 10 μg/m3 PM2.5
Air pollution as a risk factor 
Lim et al. 2013. Lancet 380: 2224-2260 
Cardiovascular 
disease 
Association between air pollution and cardiovascular 
disease are especially strong for particulate matter
What is cardiovascular disease? 
•Cardiovascular disease is the UK’s biggest killer 
–180,000 deaths in 2010 
•~103,000 heart attacks 
•~152,000 strokes 
•~25,000 new cases of heart failure 
•Annually, ambient urban air pollution is estimated to result in 3.5 million deaths worldwide!
‘From car to carotid’ 
Image by Howard Sochurek, Corbis
BHF Edinburgh Air Pollution Programme 
•British Heart Foundation Project Grant (2005 – 2015) 
•Prinicipal applicant: Prof David E. Newby 
•Aim – to bring together researchers of different disciplines to study the cardiovascular effects of (particulate) air pollution 
Cardiologists 
Dave Newby, 
Nick Mills, 
Jeremy Langrish, 
Andy Lucking, 
Anoop Shah 
Amanda Hunter 
Nick Boon, 
Keith Fox 
Cardiovascular Scientists 
Mark Miller, 
Paddy Hadoke, 
Katie Shaw, 
Steve McLean, 
Caroline Tabor 
Sarah Robertson 
Particle Toxicologist Ken Donaldson, Rodger Duffin, Jen Raftis Bill MacNee 
Collaborators: 
Flemming Cassee (RIVM) 
Thomas Sandstrom (Umea), 
Anders Blomberg (Umea) 
Ian Megson (UHI, UK) 
& many more
Project themes 
Different aspects of the cardiovascular system 
Constituents of air pollution 
Manufactured nanomaterials 
Cellular and animal models 
Real-world exposures 
Technological innovations 
Mechanisms of action 
Epidemiology
Controlled exposures
The Cardiovascular System 
Blood 
Heart 
Vessels
Blood vessel Relaxation 
5 
10 
20 
0 
5 
10 
15 
20 
25 
30 
Concentration of acetylcholine 
m 
g/min 
P<0.05 
Forearm Blood Flow 
(ml/100ml of tissue/min) 
Endothelium-dependent vasodilation 
Mills et al. Circulation 2005
Blood Clotting
Myocardial Ischaemia 
BASELINE 
J POINT 
J POINT + 60ms 
ST-SEGMENT DEPRESSION 
Worsening 
cardiac 
ischaemia
What is a heart attack? 
Dr Marc Dweck
AIR POLLUTION & HEART ATTACKS?
Atherosclerosis
Plaque Rupture
Summary 
•Air pollution is detrimental to cardiovascular health 
•Air pollution damages the cardiovascular system in multiple ways 
•Policy level interventions needed 
•We can all play a part 
–Choosing a car with an exhaust filter? 
–Use of alternative fuels? 
–Controlling your own exposure? 
–Leave the car at home. 
–Make sure you look after your heart!
Acknowledgements 
Centre for Cardiovascular Science 
Centre for Inflammation Research 
Katie Shaw 
Steven McLean 
Caroline Tabor 
Stephen Borthwick 
Kate Leyland 
James Russell 
Danny McClure 
Nick Mills 
Sarah Robertson 
Gillian Gray 
Edwin Carter 
Jen Raftis 
Keith Fox 
Nick Boon 
Paddy Hadoke 
Dave Newby 
Ken Donaldson 
Bill MacNee 
Rodger Duffin 
Umea University, Sweden 
Thomas Sandstrom 
Anders Blomberg 
Jeremy.Langrish@ed.ac.uk 
Mark.Miller@ed.ac.uk 
RIVM, Netherlands Flemming Cassee John Boere Paul Fokkens Miriam Gerlofs-Nijand
So what can we do? 
25 μg/m3 
10 μg/m3 
•Cleaner fuel sources, more efficient engines 
•Others… 
•Reduce levels of pollutants
Particle traps for exhausts 
More blood clot
Altering fuels 
Diesel fuel Cerium 
additive 
Engine 
Lesion size 
(histological analysis of serial 
sections of barchiocephalic artery) 
control DE DCeE 
0 
20 
40 
60 
80 
atherosclerotic burden 
(% of media) 
(n=8) 
Diesel fuel Exhaust 
Engine 
Small particles 
Exhaust Condensed 
particles
Personal Protection 
No mask 
mask 
Blood pressure (mmHg) 
96 
93 
Heart Rate Variability 
(RMSSD, ms) 
16.7 
14.8
Acknowledgements 
Centre for Cardiovascular Science 
Centre for Inflammation Research 
Katie Shaw 
Steven McLean 
Caroline Tabor 
Stephen Borthwick 
Kate Leyland 
James Russell 
Danny McClure 
Nick Mills 
Sarah Robertson 
Gillian Gray 
Edwin Carter 
Jen Raftis 
Keith Fox 
Nick Boon 
Paddy Hadoke 
Dave Newby 
Ken Donaldson 
Bill MacNee 
Rodger Duffin 
Umea University, Sweden 
Thomas Sandstrom 
Anders Blomberg 
Jeremy.Langrish@ed.ac.uk 
Mark.Miller@ed.ac.uk 
RIVM, Netherlands 
Flemming Cassee 
John Boere 
Paul Fokkens 
Miriam Gerlofs-Nijand
20μg/m3 
130μg/m3 
Typical particles black smoke 
now 
1950 
Traffic derived nanoparticles 
Trends in particulate air pollution 
Vehicles on UK roads 
2 million 
28 million
The health effects of air pollution 
The world-wide effects of air pollution are considerable 
MORTALITY: up to 7 million deaths per year 
MORBIDITY loss of more 5 million work days per year 
Lim et al. 2013. Lancet 380: 2224-2260 
Cardiovascular 
disease 
Association between air pollution and cardiovascular 
disease are especially strong for particulate matter
alveolus 
The pulmonary to cardiovascular signal: Three hypotheses 
capillaries 
am
The three hypotheses for the cardiovascular effects of inhaled particles 
Inflammatory 
mediators 
1. Lung Inflammation 
Combustion Derived Nanoparticles 
Lungs 
Cardiovascular Impairment 
3. Autonomic Regulation 
Regulation of 
parasympathetic: 
sympathetic 
balance 
Direct 
vascular 
interaction 
2. Particle Translocation
Adaptive Response
Atherosclerosis 
Impaired blood vessel function 
Viscous Cycle
Animal models of atherosclerosis 
brachiocephalic artery 
Area of plaque standardised to area of vascular wall 
heart 
aortic 
arch 
descending 
thoracic 
aorta 
diaphragm 
1 mm 
Red = SudanIV stained lipid 
high fat diet 
8 wk Western’ diet 
Repeated exposure to DEP to lungs 
saline instillations 
DEP instillations 
ApoE 
Mouse with atherosclerotic genetic background
Altering fuels 
Diesel fuel Cerium 
additive 
Engine 
Lesion size 
(histological analysis of serial 
sections of barchiocephalic artery) 
control DE DCeE 
0 
20 
40 
60 
80 
atherosclerotic burden 
(% of media) 
(n=8) 
Diesel fuel Exhaust 
Engine 
Small particles 
Exhaust Condensed 
particles

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Air Pollution and Cardiovascular Health Dr. Jeremy Langrish and Dr. Mark Miller

  • 1. Air Pollution and Cardiovascular Health Dr Jeremy Langrish1 & Dr Mark Miller2 1Clinical Lecturer & Specialty Registrar in Cardiology 2Senior Research Fellow Centre for Cardiovascular Sciences University of Edinburgh / Edinburgh Heart Centre Scottish Transport Emissions Partnership. “Step 2 Conference” School of Informatics, Edinburgh, 18th November 2014
  • 7. So what is air pollution? Particles Gases Volatile Liquids organic species reactive metals
  • 8. Fine and ultrafine PM Adsorbed chemicals Metals Nitrates / sulphates Organic compounds Carbon core
  • 10. Particles & Cardiorespiratory disease Risk of dying from cardiorespiratory disease increased by 37% in the most polluted as compared to the least polluted city Risk increases by 6% for each increase in 10 μg/m3 PM2.5
  • 11. Air pollution as a risk factor Lim et al. 2013. Lancet 380: 2224-2260 Cardiovascular disease Association between air pollution and cardiovascular disease are especially strong for particulate matter
  • 12. What is cardiovascular disease? •Cardiovascular disease is the UK’s biggest killer –180,000 deaths in 2010 •~103,000 heart attacks •~152,000 strokes •~25,000 new cases of heart failure •Annually, ambient urban air pollution is estimated to result in 3.5 million deaths worldwide!
  • 13. ‘From car to carotid’ Image by Howard Sochurek, Corbis
  • 14. BHF Edinburgh Air Pollution Programme •British Heart Foundation Project Grant (2005 – 2015) •Prinicipal applicant: Prof David E. Newby •Aim – to bring together researchers of different disciplines to study the cardiovascular effects of (particulate) air pollution Cardiologists Dave Newby, Nick Mills, Jeremy Langrish, Andy Lucking, Anoop Shah Amanda Hunter Nick Boon, Keith Fox Cardiovascular Scientists Mark Miller, Paddy Hadoke, Katie Shaw, Steve McLean, Caroline Tabor Sarah Robertson Particle Toxicologist Ken Donaldson, Rodger Duffin, Jen Raftis Bill MacNee Collaborators: Flemming Cassee (RIVM) Thomas Sandstrom (Umea), Anders Blomberg (Umea) Ian Megson (UHI, UK) & many more
  • 15. Project themes Different aspects of the cardiovascular system Constituents of air pollution Manufactured nanomaterials Cellular and animal models Real-world exposures Technological innovations Mechanisms of action Epidemiology
  • 17. The Cardiovascular System Blood Heart Vessels
  • 18. Blood vessel Relaxation 5 10 20 0 5 10 15 20 25 30 Concentration of acetylcholine m g/min P<0.05 Forearm Blood Flow (ml/100ml of tissue/min) Endothelium-dependent vasodilation Mills et al. Circulation 2005
  • 20. Myocardial Ischaemia BASELINE J POINT J POINT + 60ms ST-SEGMENT DEPRESSION Worsening cardiac ischaemia
  • 21. What is a heart attack? Dr Marc Dweck
  • 22. AIR POLLUTION & HEART ATTACKS?
  • 25. Summary •Air pollution is detrimental to cardiovascular health •Air pollution damages the cardiovascular system in multiple ways •Policy level interventions needed •We can all play a part –Choosing a car with an exhaust filter? –Use of alternative fuels? –Controlling your own exposure? –Leave the car at home. –Make sure you look after your heart!
  • 26. Acknowledgements Centre for Cardiovascular Science Centre for Inflammation Research Katie Shaw Steven McLean Caroline Tabor Stephen Borthwick Kate Leyland James Russell Danny McClure Nick Mills Sarah Robertson Gillian Gray Edwin Carter Jen Raftis Keith Fox Nick Boon Paddy Hadoke Dave Newby Ken Donaldson Bill MacNee Rodger Duffin Umea University, Sweden Thomas Sandstrom Anders Blomberg Jeremy.Langrish@ed.ac.uk Mark.Miller@ed.ac.uk RIVM, Netherlands Flemming Cassee John Boere Paul Fokkens Miriam Gerlofs-Nijand
  • 27. So what can we do? 25 μg/m3 10 μg/m3 •Cleaner fuel sources, more efficient engines •Others… •Reduce levels of pollutants
  • 28. Particle traps for exhausts More blood clot
  • 29. Altering fuels Diesel fuel Cerium additive Engine Lesion size (histological analysis of serial sections of barchiocephalic artery) control DE DCeE 0 20 40 60 80 atherosclerotic burden (% of media) (n=8) Diesel fuel Exhaust Engine Small particles Exhaust Condensed particles
  • 30. Personal Protection No mask mask Blood pressure (mmHg) 96 93 Heart Rate Variability (RMSSD, ms) 16.7 14.8
  • 31. Acknowledgements Centre for Cardiovascular Science Centre for Inflammation Research Katie Shaw Steven McLean Caroline Tabor Stephen Borthwick Kate Leyland James Russell Danny McClure Nick Mills Sarah Robertson Gillian Gray Edwin Carter Jen Raftis Keith Fox Nick Boon Paddy Hadoke Dave Newby Ken Donaldson Bill MacNee Rodger Duffin Umea University, Sweden Thomas Sandstrom Anders Blomberg Jeremy.Langrish@ed.ac.uk Mark.Miller@ed.ac.uk RIVM, Netherlands Flemming Cassee John Boere Paul Fokkens Miriam Gerlofs-Nijand
  • 32. 20μg/m3 130μg/m3 Typical particles black smoke now 1950 Traffic derived nanoparticles Trends in particulate air pollution Vehicles on UK roads 2 million 28 million
  • 33. The health effects of air pollution The world-wide effects of air pollution are considerable MORTALITY: up to 7 million deaths per year MORBIDITY loss of more 5 million work days per year Lim et al. 2013. Lancet 380: 2224-2260 Cardiovascular disease Association between air pollution and cardiovascular disease are especially strong for particulate matter
  • 34. alveolus The pulmonary to cardiovascular signal: Three hypotheses capillaries am
  • 35. The three hypotheses for the cardiovascular effects of inhaled particles Inflammatory mediators 1. Lung Inflammation Combustion Derived Nanoparticles Lungs Cardiovascular Impairment 3. Autonomic Regulation Regulation of parasympathetic: sympathetic balance Direct vascular interaction 2. Particle Translocation
  • 37. Atherosclerosis Impaired blood vessel function Viscous Cycle
  • 38. Animal models of atherosclerosis brachiocephalic artery Area of plaque standardised to area of vascular wall heart aortic arch descending thoracic aorta diaphragm 1 mm Red = SudanIV stained lipid high fat diet 8 wk Western’ diet Repeated exposure to DEP to lungs saline instillations DEP instillations ApoE Mouse with atherosclerotic genetic background
  • 39. Altering fuels Diesel fuel Cerium additive Engine Lesion size (histological analysis of serial sections of barchiocephalic artery) control DE DCeE 0 20 40 60 80 atherosclerotic burden (% of media) (n=8) Diesel fuel Exhaust Engine Small particles Exhaust Condensed particles