Coronary Artery Disease and Myocardial Infarction
hadreducedhealth-relatedqualityoflifeHRQoLbeneitsafterPTCAwheretheyhad notstoppedsmokingaftertheprocedure
[21] .
IncontrasttonicotinecarbonmonoxideCOispartiallyresponsibleforthedevelopment ofarteriosclerosisinsmokers.Additionally,othertoxicagentsincludedincigarettesmoke
haveapronouncedimpact [22–24]
.Experimentalanimalworkindicatesthatsuchsubstances includeformaldehyde,nitrosamines,acroleine,andNO
x
.Severalpathologicalprocessesare involvedintheaortaoffowlstreatedwithcarcinogenicagents
[25] .Smoothmusclecells
proliferateandpenetrateintotheintimaoflargervessels [25–28]
.3-Methylcholanthrene, benzo-[a]-pyreneBP,and7,12-dimethylbenzaanthraceneDMBAinitiatecomparable
intimalesionsintheaortaofchickensanddoves [25,26,29,30]
.Aortictissueofchicken containsthesubenzymeCYP
1A1
whichactivatesordetoxiiescarcinogenicsubstances [31]
, andwhichcanbeinducedbypolycyclicaromatichydrocarbonsPAH
[25,27] .CYP
1A1
is alsopresentinhumanaorticsmoothmusclecells,andthehydroxylationofBPandDMBA
hasalsobeendescribedinculturedhumanfoetalsmoothmusclecells [32]
.Thus,itseems highlylikelythatcarcinogenicagentsarepartlyresponsibleforlesionsatthevesselwalland
foractivationofbloodplatelets [33]
.
Room temp. 25.5°C
78°F
Smoking corn silk
cigaret Smoking
standard cigaret
Intravenous nicotine
Blood pressure
Pulse
120 110
100 90
80 70
60 120
110 100
90 80
70 60
Beats per min.
Control Control
Control period period
period
Temperature mm of Hg
saline, intravenous
°C 35
34 33
32 31
30 29
95.0 93.2
91.4 89.6
87.8 86.0
84.2 82.4
80.6 78.8
77.0
Toe Finger
Time in minutes
28 27
26 25
°F
Fig. 6.1
Effectofsmokingtwocornsilkorstandardcigarettesandofintravenousinjectionof2 mgnicotineonextremityskintemperature,bloodpressureandheartrateHRofonenormal
person [152]
HaematocritisadecisivefactorfortheprognosisofCHD [34]
:theassociationbetween haematocritandCHDmortalitywasassessedinthelarge-scaleNHANESIIMortalityStudy
1976–1992in8,896patientsaged30–75years,withsmokingstatusasoneofthecovari- atesincluded.Womenwithhaematocritintheuppertertilewere1.3timesCI95:0.9–1.9
morelikelytodiefromCHDthanwerewomenwithhaematocritinthelowesttertile.Since similarassociationscouldnotbedemonstratedformen,thismustbeamultifactorialphe-
nomenon [34]
. Amongthe4,000ormoretoxicsubstancesabsorbedduringsmoking,carbonmonoxide
COandglycoproteinsplayaparticularlyimportantroleinthedevelopmentofsmoking- relatedarterioscleroticchangesseeSect.
6.4 ,andtheseverityofthechangesproducedis
inluencedbythecigarettedoseandsmokingduration [35,36]
. SmokingdisturbstheO
2
supplyconsumptionratioupto15ofhaemoglobinisno longeravailableforO
2
transport,causingheartrateHRandbloodpressuretoincrease slightlyseeFig.
6.1
[35,37] .Thenicotineabsorbedwitheverycigarettepuff50–150mg
maypossiblynotbeentirelyresponsibleforthesechanges,eventhoughthealkaloiddoes producemeasurableincrementsinplasmaconcentrationsofadrenalineandnoradrenaline
[38] .Theseincreasesareverymuchsmallerinhabitualsmokersthaninoccasionalsmokers.
Also,whiletheoccurrenceofcardiacarrhythmiasaftersmokingmaybeattributabletothe effectofnicotine
[39] ,thisphenomenonisduemoretotheinhalationofothertoxicsubstances
CO,formationofCO-haemoglobin [16]
. Yearsofhabitualcigarettesmokingleadtocoronaryconstrictionandlowercoronary
reserveoneffort [40]
.InhabitualsmokerssimultaneouslysufferingfromCHD,cigarette smoking lowers the angina threshold. Just 5 min after smoking one cigarette, coronary
bloodlowisreduced7andcoronaryresistanceisincreased21,accompaniedbya simultaneousriseintherate-pressureproduct
[41] .Thesechangesarecausedbycoronary
vesselconstrictionandbytheveryrapidonsetofmyocardialhypoxia.Inanginapatients, regardlessofthenumberofcigarettessmoked,cigarettesmokingproducesnarrowingof
thecoronaryarterylumendetectableonangiography [42,43]
,andthiseffectisparticularly severeinpatientswithvasospasticangina
[44] .
Resultsconirmtheminimal“harmfulness”ofnicotineonthecirculationFig. 6.2
[45]
. Thisstudycomparedcardiovascularriskfactorsinsmokers,non-smokersandusersofsnuff
andchewingtobaccosmokelesstobacco.Smokelesstobaccoconsumptionoveraperiod ofyearsdoesnotproduceasigniicantincreaseinriskfactorsforthedevelopmentofCHD
orintheatherogenicindexFig. 6.2
[45]
.Thesedataalsopointtotheharmfuleffectsofthe combustionproductsoftobaccosmokeinthedevelopmentofcardiovasculardisease.
IntheTrialonReversingEndothelialDysfunctionTRENDStudy54patientssmok- ersandnon-smokerseachunderwentquantitativecoronaryangiographyatbaselineand
againafter6-monthfollow-uptomeasurecoronaryarterydiameterresponsestoacetyl- choline
[46,47] .Impairmentofendothelium-dependentvasodilatationbychronicsmok-
ingisclearlycausedbytobaccosmokeandnotbynicotine [48–51]
.Onestudyinvolving angiographicassessmentsovera2-yearperioddemonstratedprogressionofcoronaryath-
erosclerosisandthedevelopmentofnumerousnewcoronarylesionsinsmokers [52]
.The reducedvascularresponsee.g.measuredatthebrachialarteryisreversibleaftersmoking
cessation [48]
,andacorrelationhasbeenfoundbetweentheCOcontentofexpiredair [53]
andtheischaemiathreshold
[54] .Ifthisresponsealsoappliesforthecoronaryarteries,it
probablyexplainsthelowerincidenceofreinfarctionamongmenwhostoppedsmoking afterairstmyocardialinfarctioncomparedwiththosewhocontinuedtosmoke
[55] .
Cigarettesmokingappreciablyincreasestheriskofmyocardialinfarction.Inthemulti- centreGISSI-2Trial
[56] riskfactorsweredeterminedin916patientswithacutemyocar-
dialinfarction:bycomparisonwithlifelongnon-smokers,therelativeriskRRwas1.3 for ex-smokers, 2.0 for current smokers of less than 15 cigarettesday, 3.1 for current
smokersof15–24cigarettesday,and4.9forcurrentsmokersofmorethan25cigarettes day.Thedurationofsmokingwaslessimportantthantheageofthesmoker:belowtheage
of45years,smokersof25ormorecigarettesdayhada33-foldhigherriskcomparedwith non-smokers, whereas older smokers had smaller risks 45–54 years: 7.5-fold; 55–64
years:4.4-fold;65years:2.5-fold [56]
.InItalyabout50ofallacutemyocardialinfarc- tionscouldbedirectlyattributabletosmoking.
AccordingtotheRochesterCHDProject,astudyconductedin40–59-year-oldwomen, cigarettesmokingincreasestheriskforCHDorsuddencardiacdeath.Theoddsratiofor
theassociationbetweensteroidaloestrogenuseinnon-smokersandCHDwas0.6androse to5.1insmokers,with64ofallcasesofmyocardialinfarctionandsuddencardiacdeath
occurring in smokers [57, 58]
. A cardiac catheterisation study in 8,705 smokers also revealedanassociationbetweenthelocationofcoronarysclerosisandsmokingbehaviour:
stenosesoccurredmorecommonlyintherightcoronaryarterythanintheleftcircumlex arteryorleftanteriordescendingartery
[59] .
Accordingtoonecase-controlstudyin555womenbelowtheageof50years,theriskof myocardialinfarctionincreasedwiththenumberofcigarettessmoked,regardlessofwhether
other predisposing factors total cholesterol, HDL, oral contraceptive use, hypertension, diabetesmellituswerepresent
[60] .Therisktowomenisunderscoredbyafurtherstudy,
accordingtowhichtheriskofmyocardialinfarctionwasincreased2.47-foldinsmokersof just1–5cigarettesdaily
[61] .Theriskwasincreased74.6-foldinwomenwhowereheavy
smokers ³40 cigarettes daily; oral contraceptive use did not entail any increased risk, whereastherewereadditiveriskswithhypertensionanddiabetesmellitus
[61] .
In one study in 5,572 patients at risk compared with 6,268 controls, the coronary riskfellfrom3.5to1.5formenandfrom4.8to1.6forwomenwhohadquitsmokingfor
25
p = 0.28 p = 0.14
p 0.0001 p 0.0001
Framingham CHD Risk index
Atherogenic index
20 15
10 5
25 20
15 10
5
Fig. 6.2
Boxplotsshowingthe10th,25th,50th,75thand90thpercentilesoftheindicesforcardiovas- cularriskfactorsFraminghamCHDRiskIndexandAtherogenicIndex.ANOVAandFisher’stest
forthecomparisonofdifferenttobaccouserssmokelesstobaccousers:cross-hatchedboxes;smokers: stippledboxeswithnon-smokerswhiteboxeswerestatisticallysigniicantp0.05
[45]
1–3years [62]
.After4–6yearsofsmokingcessation,theriskwascomparablewiththatof never-smokers
[62] .Also,comparedwithnon-smokers,theirstmyocardialinfarctionhas
beenshowntooccur13.8yearsearlierinmalesmokersand3.6yearsearlierinfemale smokers
[63] .
Thedatapresentedintheliteratureindicatethatnicotineitselfexertsnoappreciable deleteriouseffectsonmyocardialperfusionorintermsofincreasingriskfactorsforCHD
[55] .Whilenicotineadministrationtoratsduringthepost-infarctionperioddoesleadto
delayedregressionofleft-ventricularchanges [64]
,itwouldbeprematuretodrawfar- reachingconclusionsfromtheseindings.