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)