Epidemiology of Morbidity and Mortality from Particles and Co-Pollutants: :
Respiratory, Cardiovascular, and Cancer
Douglas W. Dockery
Harvard School of Public Health
Estimated Effect of Each 10 g/m3 Increase in PM10
-2
0
2
4
6
8%
Cha
nge
in D
aily
Mor
talit
y Total
Respiratory
Cardiovascular
PM10 and Elderly Hospital Admissions: DetroitSchwartz & Morris, Am J Epi 1995
Daily hospital admissions of elderly (65+ yrs) for 1986-89Medicare files
32 g/m3 PM10
associated with +1.8% Ischemic HD
+2.4% Heart Failure
+1.9% Dysrythmias
CO also associate with Heart Failure
Ischemic Heart Disease
42
43
44
45
46
0 25 50 75 100
PM10 (g/m3)
Adm
issi
ons/
Day
PM Air Pollution and Cardiovascular Hospital AdmissionsSchwartz, Epidemiology1998
Hospital admission for CVD (ICD9 390-429)
Eight metropolitan counties with PM10 measurements (1988-1990)
Overall effect of 25 g/m3 PM10
2.5%(95%CI 1.8%,3.2%)-5
0
5
10
Col
orad
o Sp
rSp
okan
eTa
com
aSt
. Pau
lM
innea
polis
New
Hav
enSe
attle
Chic
ago
Tucs
on
Per
cent
Inc
reas
e in
Adm
issi
ons
Does PM Pollution Induce Hypoxemia?Pope et al, AJRCCM 1999
Do PM episodes produce transient drops in blood oxygenation?
Two panels of elderly adults at high altitude– 52 retired BYU faculty
and spouses– 38 retirement home
residents
Measured oxygen saturation in morning and evening with pulse oximeter
PM10, CO, and NO2 measured at 3 sites within valley
Four winter months 1995-96
Utah Valley - Winter 1995/96
0
20
40
60
80
100
120
140
160P
M1
0 (
g/m
3)
LindenProvoOrem
Utah Valley Oximetry StudyUtah Valley Oximetry StudyPM10
94.0
94.2
94.4
94.6
94.8
95.0
95.2
95.4
0 20 40 60 80 100 120 140
Previous Day PM10 (g/m3)M
ean
Sp
O2 (
%)
Barometric Pressure
94.0
94.2
94.4
94.6
94.8
95.0
95.2
95.4
630 635 640 645 650 655 660 665
Barometric Pressure (mm Hg)
Mea
n S
pO
2 (
%)
Utah Valley Oximetry Study
Expected association between SpO2 and barometric pressure
No association between SpO2 and PM10
Unexpected positive association between heart rate and PM10
Seen in other studies (Peters, 1999). Autonomic link?
70
72
74
76
0 50 100 150
Previous Day PM10 (g/m3)M
ean
Pu
lse (
bp
m)
Heart Rate Variability (HRV)
HRV indicator of autonomic tone
SDNN - standard deviation of time intervals between normal beats
SDNN decreases with age, lower in illness
Low SDNN associated with risk of sudden death
Decreased SDNN associated with poor cardiovascular prognosis– Framingham Study: lower
SDNN associated with higher risk of death (Tsui, Circ 1994)
Utah Valley Ambulatory ECG PilotPope et al, AHJ 1999
Panel of 6 Emeritus BYU faculty, Winter 1995/96
24 hour ambulatory ECG monitoring
Three occasions - before, during and after PM episode
Conclusions– Decreased heart rate
variability (SDNN) following episodes
– Participants unwilling to repeat measurement
50
100
150
200
250
0 50 100 150
Prev Day PM10 (g/m3)
SD
NN
HRV and PM Air PollutionHRV and PM Air Pollution
Panel studies of elderly– Ambulatory EKG monitoring – Controlled conditions (5-30 minutes)– Repeated every other day to weekly
Reported HRV associated with PM10
– Baltimore, MD (Liao et al, EHP 1999) – Boston, MA (Gold et al, Circ 2000)– Baltimore, Md (Creason et al, JEAEE2000)
Implantable Cardioverter Implantable Cardioverter Defibrillators (ICD) Devices (ICD) Devices
Implanted under skin with electrodes and leads attached to heart
Monitor cardiac rhythm abnormalities
On detecting potentially fatal arrhythmia, triggers cardioverter shock
Records date and time of all detected arrhythmias and therapies
Abstracted Arrhythmia DataAbstracted Arrhythmia Data
Date& Time of Arrhythmia
Result of Therapy
Therapy Initiated
Type of Arrhythmia
Identifier
Interval
Air Pollution and Incidence of Cardiac ArrhythmiasPeters et al, Epidemiology 2000
100 patients with Implanted Cardioverter Defibrillators (ICDs)
Lived in eastern Massachusetts
Followed 1995-1997, median 644 days
Abstracted ICD Discharges– 223 events– 33 patients with any
discharge, 6 with 10+
Daily air pollution measurements– PM10, PM2.5, black
carbon,
– CO, O3, NO2 and SO2
Weather– Temperature and
humidity Regression of ICD
discharges against air pollution
Air Pollution and Incidence of Cardiac ArrhythmiasPeters et al, Epidemiology 2000
OR for ICD Discharge associated with PM2.5, Black Carbon, and NO2
Stronger associations among 6 patients with 10+ events (effect of 5%-95% air pollution)– PM2.5 1.22 (0.7,2.0)
– BC 2.16 (1.0,4.9)
– NO2 3.13 (1.8,5.6)
PM2.5 lag 2 days
0.8
1.0
1.2
1.4
1.6
1.8
0 10 20 30
PM2.5 (g/m3)O
R f
or
ICD
Dis
char
ge
Determinants of MI Onset Study
“Determinants of Myocardial Infarction Onset Study” designed to study triggers of myocardial infarction such as exercise (Mittleman et al., NEJM 1993).
Subset of 833 patients with myocardial infarction interviewed in the greater Boston area between 1995 and 1996.
Hourly PM2.5 data available during this period (24h-average: 12.1 µg/m3; max: 47.4 µg/m3).
Acute Triggers of Myocardial Infarction?
A case-crossover study provides a framework to study triggers (Maclure, AJE 1991; Mittleman et al., AJE 1995)
Event
case-periodcontrol-periods
time (days)
Hourly PM2.5 and onset of myocardial infarction
24h-average PM2.5 and onset of myocardial infarction
OR for MI Onset for Both Time Scales OR for MI Onset for Both Time Scales SimultaneouslySimultaneously
2 Hr PM2.5
0.8
1.0
1.2
1.4
1.6
1.8
PM2.5 (g/m3)
OR
fo
r M
I O
ns
et
24 Hr PM2.5
0.8
1.0
1.2
1.4
1.6
1.8
PM2.5 (g/m3)O
R f
or
MI O
ns
et
Onset Study - Conclusions
Increased risk of MI with increased PM2.5 two hours and twenty four hours prior.
Two time scales independent and additive. Multivariate adjustments for season,
temperature and relative humidity slightly increased estimates.
Stronger effects observed for PM2.5 than for gaseous pollutants such as CO, NO2 or SO2.
PM Episode & CRP Acute Phase ResponseMONICA - Augsburg Study
Peters et al, 2000
631 men 45-64 yrs, tested 1984/85 and 1987/88
C Reactive Protein (CRP)– Imflamation, tissue damage,
infection
Jan 85 pollution episode % with CRP >5.7 mg/L
– episode (17%)
– nonepisode (11%)
– follow-up (8%)
CRP > 5.7 mg/L
0.5
1.0
1.5
2.0
2.5
0 25 50 75 1005 Day TSP (ug/m3)
OR
Population Studies of PM-Induced Population Studies of PM-Induced Changes in Cardiac FunctionChanges in Cardiac Function
Time Series studies Cardiovascular mortality Cardiovascular hospital admissions
Autonomic cardiac function in elderly Pulse Rate and Heart Rate Variability
Implanted Cardiac Defibrillators Cardiac arrhythmias (VF)
Onset of myocardial infarction Inflammatory markers (CRP)