Traffic deaths

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Hi All,

Does traffic get you down? Do not let it get you under

the turf.

Pdfs of the below are available.

N Engl J Med 2004;351:1721-30.

Exposure to Traffic and the Onset of Myocardial Infarction

Annette s,Ph.D., von Klot,M.P.H.,Margit Heier,M.D.,

background

An association between exposure to vehicular traffic in urban areas

and the exacerba-

tion of cardiovascular disease has been suggested in previous

studies.This study was

designed to assess whether exposure to traffic can trigger myocardial

infarction.

methods

We conducted a case –crossover study in which cases of myocardial

infarction were

identified with the use of data from the ative Health Research

in the Region of

Augsburg Myocardial Infarction Registry in Augsburg,in southern

Germany,for the

period from February 1999 to July 2001.There were 691 subjects for

whom the date

and time of the myocardial infarction were known who had survived for

at least 24

hours after the event,completed the registry 's standardized

interview,and provided in-

formation on factors that may have triggered the myocardial

infarction.Data on sub-

jects ' activities during the four days preceding the onset of

symptoms were collected

with the use of patient diaries.

results

An association was found between exposure to traffic and the onset of

a myocardial in-

farction within one hour afterward (odds ratio,2.92;95 percent

confidence interval,

2.22 to 3.83;P<0.001).The time the subjects spent in cars,on public

transportation,or

on motorcycles or bicycles was consistently linked with an increase

in the risk of myo-

cardial infarction.Adjusting for the level of exercise on a bicycle

or for getting up in the

morning changed the estimated effect of exposure to traffic only

slightly (odds ratio for

myocardial infarction,2.73;95 percent confidence interval,2.06 to

3.61;P<0.001).

The subject 's use of a car was the most common source of exposure to

traffic;neverthe-

less,there was also an association between time spent on public

transportation and the

onset of a myocardial infarction one hour later.

conclusions

Transient exposure to traffic may increase the risk of myocardial

infarction in suscepti-

ble persons.

Supported by a research agreement (98-4)with the Health Effects

Institute,Boston,by the GSF –National Research Center for Envi-

ronment and Health,Neuherberg,Germany,and by a grant (R-

827354)from the Environmental Protection Agency (to Drs.s

and Wichmann).

N Engl J Med 2004;351:1716-1718

Triggering Myocardial Infarction

H.Stone,M.D.

Related article,page 1721

Enormous progress made during the past few de-

cades has dramatically enhanced our understanding

of the pathobiology and pathophysiology responsi-

ble for acute myocardial infarction.Investigations

in vascular biology have elucidated the critical role

of growth factors,the proliferation of smooth-

muscle cells,and the central role of inflammation

in the initiation and progression of atherosclero-

sis.1 Research has also focused on the initiating

events or " triggers " that qualitatively alter the sta--

ble or quiescent phase of coronary atherosclerosis

and initiate a cascade of events that culminates in

acute myocardial infarction.Some triggering phe-

nomena may exert a single,transient effect on the

pathophysiologic process,such as a surge of sym-

pathetic activity,whereas others exert a more varied

and pervasive effect,amplifying risk at multiple

points and over a longer period.In this issue of the

Journal,s et al.(pages 1721 –1730)provide

compelling epidemiologic evidence that particulate

air pollution from traffic may trigger the abrupt

onset of acute myocardial infarction.An under-

standing of air pollution in the larger context of

triggering of the entire process of atherosclerosis

suggests,in addition,that air pollution plays a more

complex and multifaceted role in the development

of cardiovascular disease over the longer term.

As initially described 15 years ago,the trigger-

ing of acute myocardial infarction typically begins

with the so-called vulnerable or high-risk coronary

atherosclerotic plaque,a focal lesion in jeopardy of

plaque disruption.2 The vulnerable plaque is usually

an inflamed,thin-cap fibroatheroma,characterized

by a lipid-rich,atheromatous core with cholesterol

crystals and necrotic debris,a thin fibrous cap with

an infiltration of macrophages and lymphocytes,

and decreased smooth-muscle-cell content,and

associated with expansive remodeling of the outer

vessel wall.3 The inflammatory cells associated with

this type of high-risk plaque express a variety of cy-

tokines and chemokines that contribute to inflam-

mation and oxidative stress,as well as matrix me-

talloproteinases that can degrade the extracellular

matrix,thereby weakening the plaque 's fibrous cap

and rendering it prone to rupture.Other,less com-

mon,coronary plaques that are prone to disruption

may be characterized by extensive proliferation of

smooth-muscle cells in a proteoglycan-rich matrix

without the accompanying intense inflammation

and thin fibrous cap;in such cases,a thrombus may

form from a superficial erosion of the endothelial

surface.

In persons with such a pathobiologic substrate

of vulnerable plaque,the initiating event or trigger

that may lead to the disruption of the plaque is

often an external activity associated with increased

sympathetic stimulation,such as physical or emo-

tional stress or vasoconstriction.This trigger may

lead very rapidly to the rupture of the vulnerable

plaque,exposing the bloodstream to the thrombo-

genic contents of the plaque or the denuded endo-

thelial surface,leading to rapid thrombus formation

and,consequently,acute myocardial infarction.An

additional trigger or initiating process,such as a

transient increase in coagulability,inflammation,

viscosity,or vasoconstriction,may further predis-

pose to the formation of a thrombus.

Recently,it has been suggested that the sites at

which triggers contribute to the development of

acute myocardial infarction can be extended proxi-

mally in the pathophysiologic process 4 (see Figure).

Although atherosclerosis may affect the coronary

tree diffusely,the principal manifestations of coro-

nary plaque are highly focal.In a susceptible person

with an adverse risk-factor profile,local hemody-

namic disturbances,such as small areas of dis-

turbed coronary blood flow and low shear stress,

constitute the initiating event or trigger leading to

focal atherosclerotic plaque formation and progres-

sion,which may continue for years.Although there

may be many such areas of intimal thickening in

early stages of atherosclerosis,only a subgroup,and

perhaps a very small subgroup,of these coronary

plaques become inflamed or vulnerable at any one

time.Other plaques may acquire characteristics of

fibrosis and scarring,and still others may remain

quiescent.

The triggering factors that determine which of

those early plaques will progress and become in-

flamed are unknown,but it is likely that local he-

modynamic factors,local vascular-remodeling re-

sponses,and the degree of systemic inflammation

all contribute.Plaques that are inflamed and prone

to rupture are those in which there is expansive or

outward remodeling of the arterial wall,whereas

those that are more fibrotic and scarred,without

active inflammation,are associated with constric-

tive or inward remodeling.The divergent vascular-

remodeling characteristics most likely reflect the

balance in the dynamic regulation of collagen syn-

thesis and breakdown.

Epidemiologic studies have long demonstrated

the increased cardiac morbidity and mortality as-

sociated with particulate air pollution,and recent

investigations have focused on the mechanistic role

of air pollution in cardiovascular disease.5 Inhala-

tion of particulate air pollution into the lungs leads

to both pulmonary and systemic inflammation,with

induction of cytokines and chemokines and gener-

ation of oxidative species.These injurious mole-

cules create and exacerbate inflammation and oxi-

dative stress,which lead to direct vascular injury,

atherosclerosis,and autonomic dysfunction.Partic-

ulate air pollution also rapidly leads to a significant

increase in fibrinogen,plasma viscosity,and platelet

activation,as well as the release of endothelins,a

family of potent vasoconstrictor molecules.Studies

in animals have clearly documented the short-and

long-term adverse effects of particulate air pollution

on each step of the triggering cascade of coronary

disease culminating in acute myocardial infarction:

accelerated atherosclerosis,vasoconstriction,and

increased thrombogenesis.

The association between exposure to traffic and

the abrupt onset of myocardial infarction described

by s et al.suggests that particulate air pollution

from traffic may have led to abrupt plaque disrup-

tion and perhaps to the exacerbation of a thrombo-

genic environment.Transient,intense inflamma-

tion,vasoconstriction,and increased coagulability,

alone or in combination,are potential culprits in

this process.

In addition to these extremely short-term effects

of particulate air pollution,its deleterious longer-

term effects on the entire gamut of atherosclerotic

triggers cannot be overemphasized.Decades of ep-

idemiologic evidence underscore the cardiovascu-

lar morbidity and mortality related to air pollution.

The proinflammatory,proatherosclerotic,and pro-

thrombotic effects of particulate air pollution are

compelling.As both epidemiologic and now mech-

anistic evidence mounts,there is greater urgency to

accelerate our efforts to reduce particulate air pol-

lution and to improve cardiovascular health.

Dr.Stone reports having received grant support from Boston Sci-

entific and Pfizer.

1.Libby P.Inflammation in atherosclerosis.Nature 2002;420:

868-74.

2.Muller JE,Tofler GH,Stone PH.Circadian variation and trig-

gers of onset of acute cardiovascular disease.Circulation 1989;

79:733-43.

3.Virmani R,Kolodgie FD,Burke AP,Farb A,Schwartz SM.Les-

sons from sudden coronary death:a comprehensive morpholog-

ical classification scheme for atherosclerotic lesions.Arterioscler

Thromb Vasc Biol 2000;20:1262-75.

4.Stone PH,Coskun AU,Yeghiazarians Y,et al.Prediction of

sites of coronary atherosclerosis progression:in vivo profiling of

endothelial shear stress,lumen,and outer vessel wall character-

istics to predict vascular behavior.Curr Opin Cardiol 2003;18:

458-70.

5.Brook RD,lin B,Cascio W,et al.Air pollution and car-

diovascular disease:a statement for healthcare professionals

from the Expert Panel on Population and Prevention Science of

the American Heart Association.Circulation 2004;109:2655-71.

Cheers, Alan Pater.