The Cardiologist’s Guide to the The Cardiologist’s Guide to the Cardiovascular Consequences of Cardiovascular Consequences of

Smoking and the Benefits of CessationSmoking and the Benefits of Cessation

OverviewOverview

Coronary artery diseaseCoronary artery disease

Peripheral vascular disease Peripheral vascular disease

Abdominal aortic aneurysmAbdominal aortic aneurysm

StrokeStroke

Cardiovascular disease and environmental Cardiovascular disease and environmental tobacco smoketobacco smoke

Cardiovascular benefits of smoking cessationCardiovascular benefits of smoking cessation

Smoking and Coronary Artery DiseaseSmoking and Coronary Artery Disease (CAD) (CAD)

Smoking: Role in the Pathogenesis of Smoking: Role in the Pathogenesis of Cardiovascular EventsCardiovascular Events

Endothelial dysfunctionEndothelial dysfunction

Increased hematologic Increased hematologic thrombogenicitythrombogenicity

Enhanced inflammatory Enhanced inflammatory responseresponse

Oxidative modificationOxidative modification

Lavi et al. Circulation. 2007;115:2621-2627; http://www.texasheartinstitute.org/HIC/Topics/Diag/diangio.cfm. Accessed June 14, 2007.

Atherosclerotic Disease Right Coronary Artery

Smoking: Increased ThrombogenicitySmoking: Increased Thrombogenicity

Tissue factor (TF) is highly Tissue factor (TF) is highly expressed in atherosclerotic expressed in atherosclerotic plaques and may play a role plaques and may play a role in thrombosisin thrombosis

TF was assessed by adding TF was assessed by adding factor Xa (FXa)factor Xa (FXa)

Current smokers have Current smokers have significantly higher levels of significantly higher levels of circulating TF activity than circulating TF activity than nonsmokersnonsmokers

Sambola et al. Circulation. 2003;107:973-977.

217

283

0

100

200

300

400

CurrentSmokers Priorto Smoking 2

Cigarettes

CurrentSmokers After

Smoking 2Cigarettes

Fac

tor

Xa

(FX

a) p

mo

l/L

/min

P=.003

Smoking: Impaired Endothelial Vasodilator FunctionSmoking: Impaired Endothelial Vasodilator Function

Zeiher et al. Circulation. 1995;92:1094-1100.

Flo

w-D

epen

den

t D

ilat

ion

(%

)

0

20

30

40

60

50

10

–10

P<.01

P<.001

P<.01

Current Smokers

P<.01

Nonsmokers

P<.01

Flow-dependent dilation was Flow-dependent dilation was significantly blunted in current significantly blunted in current smokers compared with nonsmokers smokers compared with nonsmokers Angiographically normal smokers

Angiographically irregular smokers

Angiographically normal nonsmokers

Angiographically irregular nonsmokers

Smoking: Epicardial Endothelial Smoking: Epicardial Endothelial DysfunctionDysfunction

Lavi et al. Circulation. 2007;115:2621-2627.

Current smokers are more likely to have epicardial endothelial Current smokers are more likely to have epicardial endothelial dysfunction than nonsmokersdysfunction than nonsmokers

En

do

thel

ial

Dys

fun

ctio

n (

%)

P=.0360

45

30

15

0Nonsmokers Ex-smokers Current

Smokers

46%

34%35%

Smoking: Elevated White Blood Cell CountSmoking: Elevated White Blood Cell Count Elevated white blood cell (WBC) count has been associated with a greater Elevated white blood cell (WBC) count has been associated with a greater

risk of cardiovascular eventsrisk of cardiovascular events

Current smokers have significantly increased WBC counts compared with Current smokers have significantly increased WBC counts compared with nonsmokersnonsmokers

Lavi et al. Circulation. 2007;115:2621-2627; Stewart et al. Circulation. 2005;111:1756-1762

8

6

4

2

0

P<.0001

P=.03

P<.0001

P<.0001Cel

l C

ou

nts

(10

9 /L

)

Current Smokers

Ex-smokers

WBC Neutrophils Lymphocytes Monocytes

Nonsmokers

Smoking: Increased Oxidative ModificationSmoking: Increased Oxidative Modification

aF2-isoprostane level is an index of lipid peroxidation in vivo. The dots representing subjects who smoked are each connected to a dot representing a nonsmoker matched to the subject for age and sex.Adapted from Morrow et al. N Engl J Med. 1995;332(18):1198-1203.

640

560

480

400

320

240

160

80

Current Smokers

Nonsmokers

Fre

e F

2-Is

op

rost

anes

a (p

mo

l/L

) 1000

900

800

700

600

500

400

300

Current Smokers

Nonsmokers

Est

erif

ied

F2-

Iso

pro

stan

esa

(pm

ol/

L)

Smoking: Reduced Nitric Oxide (NO) Smoking: Reduced Nitric Oxide (NO) BiosynthesisBiosynthesis

Barua et al. Circulation. 2001;104:1905-1910.

5000

0Nonsmokers Current Smokers

4000

3000

2000

1000

NO

Co

nce

ntr

atio

n (

nm

ol/

L) P<.0001

1266

3613

Smoking: Multiplicative Risk Factor for Smoking: Multiplicative Risk Factor for Coronary Artery DiseaseCoronary Artery Disease

a All rates were age-adjusted by 10-year age groups to the US white male population in 1980. Hypercholesterolemia defined as cholesterol 250 mg/dL. Hypertension defined as a diastolic blood pressure 90 mm Hg. Burns. Prog Cardiovasc Dis. 2003;46(1): 11-29; Source: Pooling Project Research Group, 1978.

Smoking PlusElevated Cholesterol

or Hypertension

Risk Factor Status at Entry Into the Study

ElevatedCholesterol Plus

Hypertension

All 3 Risk Factors Present

Smoking, Elevated Cholesterol, or

Hypertension Alone

No RiskFactors

Rat

es p

er 1

000a

23

54

10392

189

0

50

100

150

200

250

Smoking: Increased Coronary Artery Smoking: Increased Coronary Artery Disease (CAD) MortalityDisease (CAD) Mortality

a The probability of an event (developing a disease) occurring in exposed people compared with the probability of the event in nonexposed people. Adjusted for age.Willett et al. N Engl J Med. 1987;317(21):1303-1309.

1.0

5.4

3.7

1.7

0

2

4

6

8

10

12

Rel

ativ

e R

isk

(95%

CI)

Rel

ativ

e R

isk

(95%

CI)

a

Fatal CADFatal CAD

1-14/Day1-14/DayNonsmokersNonsmokers 15-24/Day15-24/Day 25/Day25/DayCigarettes/Day

Current Smokers

Smoking: Effect on Coronary Artery Smoking: Effect on Coronary Artery DiseaseDisease

Waters et al. Circulation. 1996;94:614-621.

0

10

20

30

40

50

60

Progression of Existing Lesions

Pat

ien

ts (

%)

Current Smokers

Nonsmokers0

10

20

30

40

50

60

Formation of New Lesions

Pat

ien

ts (

%)

Current Smokers

Nonsmokers

P=.002 P=.007

5757

3737 3636

2020

Smoking: Increased Risk of AnginaSmoking: Increased Risk of Angina

aThe probability of an event (developing a disease) occurring in exposed people compared with the probability of the event in nonexposed people. Adjusted for age.Willett et al. N Engl J Med. 1987;317(1):1303-1309.

0

1

2

3

4

5

Rel

ativ

e R

isk

(95%

CI)

Rel

ativ

e R

isk

(95%

CI)

aa

1.01.0

1.61.6

2.62.6

2.02.0

1-14/Day1-14/DayNonsmokersNonsmokers 15-24/Day15-24/Day 25/Day25/DayCigarettes/Day

Current Smokers

Smoking: Increased Risk of Acute Smoking: Increased Risk of Acute Nonfatal Myocardial InfarctionNonfatal Myocardial Infarction Current smoking was associated with a 3-fold increase in odds of a Current smoking was associated with a 3-fold increase in odds of a

nonfatal acute myocardial infarction compared with nonsmokersnonfatal acute myocardial infarction compared with nonsmokers

aThe ratio of the odds of development of disease in exposed persons to the odds of development of disease in nonexposed persons.Teo. Lancet. 2006;368:647-658.

Odd

s R

atio

(95%

CI)

Odd

s R

atio

(95%

CI)aa

101099887766554433221100

Age <40 y Age <40 y Age 40-49 y Age 40-49 y Age 50-59 y Age 50-59 y Age 60-69 y Age 60-69 y Age >70 y Age >70 y

2200

NonsmokersNonsmokers Ex-smokersEx-smokers 1-191-19

Smoking: Increased Risk of Sudden Smoking: Increased Risk of Sudden Cardiac DeathCardiac Death

aThe probability of an event (developing a disease) occurring in exposed people compared with the probability of the event in nonexposed people. Adjusted for age.Wannamethee et al. Circulation. 1995;91:1749-1756.

1.0

2.3

0.0

1.0

2.0

3.0

4.0

Nonsmokers Current Smokers

Rel

ativ

e R

isk

(95%

CI)

Rel

ativ

e R

isk

(95%

CI)

aa

Smoking: Increased Risk of Q-Wave MI After Smoking: Increased Risk of Q-Wave MI After Percutaneous Coronary RevascularizationPercutaneous Coronary Revascularization

aThe probability of an event (developing a disease) occurring in exposed people compared with the probability of the event in nonexposed people. Adjusted for the baseline variables significantly associated with each end point.Hasdai et al. N Engl J Med. 1997;336:755-761.

0.0

1.0

2.0

3.0

4.0

Nonsmokers Ex-smokers Current Smokers

Q-wave Myocardial Infarction (MI)

Rel

ativ

e R

isk

(95%

CI)

a

1.01.01.281.28

2.082.08

Summary: Smoking and Coronary Artery Summary: Smoking and Coronary Artery Disease (CAD)Disease (CAD) Smoking plays a role in the development of CAD via:Smoking plays a role in the development of CAD via:

– Endothelial dysfunctionEndothelial dysfunction– Increased thrombogenicityIncreased thrombogenicity– Elevated WBC countsElevated WBC counts– Increased oxidative stressIncreased oxidative stress– Reduced NO biosynthesisReduced NO biosynthesis

Smoking acts as a multiplicative risk factor for Smoking acts as a multiplicative risk factor for development of CADdevelopment of CAD

Smoking is associated with an increasedSmoking is associated with an increased– Rate of progression of CADRate of progression of CAD– Risk of anginaRisk of angina– Risk of acute myocardial infarctionRisk of acute myocardial infarction– Risk of sudden cardiac deathRisk of sudden cardiac death– Risk of Q-wave myocardial infarction after Percutaneous Risk of Q-wave myocardial infarction after Percutaneous

Coronary RevascularizationCoronary Revascularization

Smoking and Peripheral Vascular DiseaseSmoking and Peripheral Vascular Disease

Peripheral Vascular Disease (PVD)Peripheral Vascular Disease (PVD)

PVD affects approximately PVD affects approximately 20% of adults older than 20% of adults older than age 55age 55

Approximately half of patients Approximately half of patients with PVD are asymptomaticwith PVD are asymptomatic

5% to 10% of asymptomatic 5% to 10% of asymptomatic patients will progress to patients will progress to symptomatic PVD over symptomatic PVD over 5 years 5 years

Patients with symptomatic Patients with symptomatic PVD are at higher risk for PVD are at higher risk for other cardiovascular disease other cardiovascular disease and mortalityand mortality

Hankey et al. JAMA. 2006;295:547-553; Hooi et al. Am J Epidemiol. 2001;153:666-672; Hooi et al. Br J Gen Pract. 1999;49:49-55; Hooi et al. Scand J Prim Health Care. 1998;16:177-182; http://healthguide.howstuffworks.com/peripheral-artery-disease-and-intermittent-claudication-in-depth.htm. Accessed October 8, 2007.

Build-up of atheroscleroticplaque in arterial wall

Asymptomatic Peripheral Vascular Asymptomatic Peripheral Vascular Disease: Increased RiskDisease: Increased Risk

aThe ratio of the odds of development of disease in exposed persons to the odds of development of disease in nonexposed persons. Adjusted for other cardiovascular risk factors. Hooi et al. Scand J Prim Health Care. 1998;16:177-182.

1.0

2.8

1.6

0.0

1.0

2.0

3.0

4.0

Od

ds

Rat

io (

95%

CI)

Od

ds

Rat

io (

95%

CI)

aa

Ex-smokers Current SmokersNonsmokers

Intermittent Claudication (IC): Increased Intermittent Claudication (IC): Increased RiskRisk Rate of development of IC is Rate of development of IC is

approximately 4 times as great in approximately 4 times as great in current smokers than in current smokers than in nonsmokers (OR 4.1[2.3-7.9]) nonsmokers (OR 4.1[2.3-7.9])

Risk tends to increase with the Risk tends to increase with the intensity of smokingintensity of smoking

The 5-year mortality for patients The 5-year mortality for patients with IC who continue to smoke is with IC who continue to smoke is 40% to 50%40% to 50%

Hooi et al. Scand J Prim Health Care. 1998;16:177-182; Kannel et al. Geriatrics. 1973;28:61-68; http://www.radiologyassistant.nl/en/42c2527422d06.

Stenosis of the Left Iliac Artery

Risk of Peripheral Vascular Disease vs Risk of Peripheral Vascular Disease vs Coronary Artery DiseaseCoronary Artery Disease For smokers, the risk of peripheral vascular disease (PVD) is greater For smokers, the risk of peripheral vascular disease (PVD) is greater

than the risk of coronary artery disease (CAD)than the risk of coronary artery disease (CAD)

aThe probability of an event (developing a disease) occurring in exposed people compared with the probability of the event in nonexposed people. Adjusted for age and sex.Price et al. Eur Heart J. 1999;20(5):344-353.

3.94

1.871.661.59

0

2

4

6

8PVD CAD

Rel

ativ

e R

isk

(95%

CI)

a

Moderate Smokers Heavy Smokers

Peripheral Vascular Disease: ProgressionPeripheral Vascular Disease: Progression

Smoking is the most important risk Smoking is the most important risk factor for the progression factor for the progression of peripheral vascular disease (PVD)of peripheral vascular disease (PVD)

Symptoms of PVD occur Symptoms of PVD occur approximately a decade earlier in approximately a decade earlier in smokers than nonsmokerssmokers than nonsmokers

Smokers with PVD have twice the Smokers with PVD have twice the amputation rate of nonsmokersamputation rate of nonsmokers

MyFootShop Peripheral VascularDisease.http://www.myfootshop.com/detail.asp?Condition=Peripheral%20Vascular%20Disease. Accessed October 19, 2007; Bendermacher et al. J Thromb Haem. 2005;3:1628-37; Dormandy et al. J Vasc Surg. 2000;31(1 pt 2):S1-296.

Lower Extremity Bypass Grafts: Increased Lower Extremity Bypass Grafts: Increased Risk of Graft FailureRisk of Graft Failure

Peto ORa

95% CIWeight

%Peto ORa

95% CI

WrayGreenhalghHerringProvanRutherfordAmeliWisemanPowellCheshireGiswoldSubtotal (95% CI)

1.261.771.292.76

10.223.795.572.951.865.72

37.19

6.4614.55

1.984.381.963.892.902.365.183.043.09

(1.42, 29.30)(4.06, 52.14)(0.44, 8.85)(1.58, 12.19)(1.15, 3.34)(1.62, 9.30)(1.41, 5.95)(0.88, 6.35)(1.49, 17.95)(1.50, 6.19)(2.34, 4.08)

Prospective Patency Studies

0.5 1 2 5 10Favors Treatment Favors Control

0.2

aAn approximation to the exact OR that is used when doing a meta-analysis using the Peto method.Willigendael et al. J Vasc Surg. 2005;42:67-74.

Smoking: Increased Mortality After Smoking: Increased Mortality After Vascular SurgeryVascular Surgery

In order to provide very late In order to provide very late survival data, Kazmers et al survival data, Kazmers et al evaluated 310 patients evaluated 310 patients undergoing elective vascular undergoing elective vascular surgerysurgery

Follow-up was 6.64Follow-up was 6.644.62 years4.62 years

Age, diabetes, smoking, and Age, diabetes, smoking, and low ejection fraction were low ejection fraction were independently associated with independently associated with overall mortality postoperatively overall mortality postoperatively

Kazmers et al. J Surg Res. 2002;105:109-114.

Summary: Smoking and Peripheral Summary: Smoking and Peripheral Vascular Disease (PVD)Vascular Disease (PVD)

Smoking is associated with an increased risk of Smoking is associated with an increased risk of – Asymptomatic PVDAsymptomatic PVD– Intermittent claudicationIntermittent claudication– Progression of PVDProgression of PVD– Amputation due to complications of PVDAmputation due to complications of PVD– Femoral-popliteal bypass graft failureFemoral-popliteal bypass graft failure– Mortality after vascular surgeryMortality after vascular surgery

Symptoms of PVD occur approximately a decade earlier Symptoms of PVD occur approximately a decade earlier in smokers than in nonsmokersin smokers than in nonsmokers

Current smokers are at greater risk for developing PVD Current smokers are at greater risk for developing PVD than coronary artery diseasethan coronary artery disease

Smoking and Abdominal Aortic Aneurysm Smoking and Abdominal Aortic Aneurysm (AAA)(AAA)

1.0

4.7

3.0

0

1

2

3

4

5

6

7

8

AAA: Greater Risk in Smokers Than CAD or AAA: Greater Risk in Smokers Than CAD or Cerebrovascular DiseaseCerebrovascular Disease The association between smoking and aortic aneurysm is substantially stronger than The association between smoking and aortic aneurysm is substantially stronger than

the association between smoking and coronary or cerebrovascular diseasethe association between smoking and coronary or cerebrovascular disease

AAA= Abdominal Aortic Aneurysm; CAD=Coronary Artery DiseaseaThe probability of an event (developing a disease) occurring in exposed people compared with the probability of the event in nonexposed people.Lederle et al. J Vasc Surg. 2003(2);38:329-334.

Aortic Aneurysm to CAD

Aortic Aneurysm to Cerebrovascular

Disease

NeverSmokers

Po

ole

d E

stim

ates

of

Rat

io o

f C

urr

ent

Sm

oke

rs’

RR

a

P<.00001

Smoking and AAA: Increased RiskSmoking and AAA: Increased Risk

AAA= Abdominal Aortic AneurysmaThe ratio of the odds of development of disease in exposed persons to the odds of development of disease in nonexposed persons. Adjusted for age and sex.Vardulaki et al. Br J Surg. 2000;87(2):195-200.

1.0

5.5

0.7

3.0 2.9

0.0

3.0

6.0

9.0

12.0

Od

ds

Rat

io (9

5% C

I)a

Nonsmokers 1 to 9 10 to 19 2520 to 24

Cigarettes/DayCurrent Smokers

1.00

2.302.00

1.40

0

1

2

3

Smoking: Increased Progression of Smoking: Increased Progression of Aortic AtherosclerosisAortic Atherosclerosis

aThe probability of an event (developing a disease) occurring in exposed people compared with the probability of the event in nonexposed people. Adjusted for age, systolic blood pressure, serum total cholesterol, Quetelet index, diabetes mellitus, menopausal status, alcohol consumption, use of replacement estrogens, and duration of follow-up.Witteman et al. Circulation. 1993;88(part 1):2156-2162.

Rel

ativ

e R

isk

(95%

CI)

a

Never Smokers 1 to 9 10 to 19 20

Cigarettes/DayCurrent Smokers

Smoking: Effect on AAA ExpansionSmoking: Effect on AAA Expansion

AAA= Abdominal Aortic AneurysmBrady. Circulation. 2004;110:16-21.

P<.001

Ave

rag

e L

inea

r G

row

th R

ate

(mm

/yea

r)

2.532.83

0.0

0.5

1.0

1.5

2.0

2.5

3.0

Nonsmokers Current Smokers

Summary: Smoking and Abdominal Summary: Smoking and Abdominal Aortic Aneurysm (AAA)Aortic Aneurysm (AAA)

Current smokers have a higher risk of developing an Current smokers have a higher risk of developing an AAA than either coronary artery disease or AAA than either coronary artery disease or cerebrovascular diseasecerebrovascular disease

Smoking is associated with an increased risk ofSmoking is associated with an increased risk of– Formation of AAAFormation of AAA– Progression of aortic atherosclerosisProgression of aortic atherosclerosis– Expansion of AAAExpansion of AAA

Smoking and StrokeSmoking and Stroke

Smoking and StrokeSmoking and Stroke

Smoking contributes to Smoking contributes to 12% to 14% of all stroke deaths12% to 14% of all stroke deaths

Smoking may potentiate the effects Smoking may potentiate the effects of other stroke risk factorsof other stroke risk factors

Smoking increases stroke riskSmoking increases stroke risk– Acutely: effects on thrombus Acutely: effects on thrombus

formationformation– Chronically: increased burden Chronically: increased burden

of atherosclerotic diseaseof atherosclerotic disease

MRI of BrainWith an Acute Ischemic Stroke

Goldstein et al. Stroke. 2006;37:1583-1633; http://www.ucihs.uci.edu/stroke/whatisastroke.shtml. Accessed October 19, 2007.

20

30

40

50

Smoking: Increased Progression of Smoking: Increased Progression of Carotid AtherosclerosisCarotid Atherosclerosis BBoth active smoking and environmental tobacco smoke exposure are oth active smoking and environmental tobacco smoke exposure are

associated with increased progression of carotid atherosclerosis.associated with increased progression of carotid atherosclerosis.

aAdjusted for demographic characteristics, cardiovascular risk factors, and lifestyle variables (risk factor model and Keys score, education, leisure activity, body mass index, and alcohol use). bTo environmental tobacco smoke.Howard et al. JAMA. 1998;279(2):119-124.

Ex-smokers with

Exposureb

CurrentSmokers

Nonsmokerswithout

Exposureb

Pro

gre

ssio

n o

f In

tim

a-M

edia

l T

hic

knes

s, µ

m/3

y (

95%

CI)

a

Ex-smokerswithout

Exposureb

Nonsmokerswith

Exposureb

43.043.0

38.838.8

31.631.6 32.832.8

25.925.9

Smoking: Increased Risk of Fatal and Smoking: Increased Risk of Fatal and Nonfatal Stroke in WomenNonfatal Stroke in Women

1.0

3.8

2.92.5

0

1

2

3

4

5

6

1-14 15-24Nonsmokers

Rel

ativ

e R

isk

(95%

CI)

a

aThe probability of an event (developing a disease) occurring in exposed people compared with the probability of the event in nonexposed people. Adjusted for age, follow-up period, history of diabetes, hypertension, high cholesterol levels, and relative weight (in 5 categories).Colditz et al. N Engl J Med. 1988;318(15):937-941.

≥25

Cigarettes/DayCurrent Smokers

0

2

4

6

8

10

12

Smoking: Increased Risk of Hemorrhagic Smoking: Increased Risk of Hemorrhagic StrokeStroke

aThe probability of an event (developing a disease) occurring in exposed people compared with the probability of the event in nonexposed people.Adjusted for age, exercise, alcohol consumption, body mass index, history of hypertension, and history of diabetes. Kurth et al. Stroke. 2003;34:2792-2795.

Total Hemorrhagic Stroke

Rel

ativ

e R

isk

(95%

CI)

a

Intracerebral Hemorrhage

Subarachnoid Hemorrhage

Nonsmokers (n=20,339)

<15 Cigarettes/day (n=1914)

15 Cigarettes/day (n=3265)

2.062.06

3.433.43 2.392.39 2.892.891.741.74 4.044.04

Smoking: Increased Stroke MortalitySmoking: Increased Stroke Mortality

Cigarette smoking increases the risk of mortality from stroke in menCigarette smoking increases the risk of mortality from stroke in men

aTwenty-year age-adjusted mortality per 10,000 person-years for men. P<.014 for trend. Hart et al. Stroke. 1999;30:1999-2007.

30.9

39.0

50.6

0

10

20

30

40

50

60

15-241-15

Mo

rtal

ity

Rat

ea

≥25

Cigarettes/DayCurrent Smokers

Summary: Smoking and StrokeSummary: Smoking and Stroke

Smoking contributes to 12% to 14% of all stroke deathsSmoking contributes to 12% to 14% of all stroke deaths

Increased risk ofIncreased risk of– Progression of carotid atherosclerosisProgression of carotid atherosclerosis– StrokeStroke– Hemorrhagic strokeHemorrhagic stroke– Intracerebral hemorrhageIntracerebral hemorrhage– Subarachnoid hemorrhageSubarachnoid hemorrhage

Increased stroke-related mortalityIncreased stroke-related mortality

Cardiovascular Disease (CVD) and Cardiovascular Disease (CVD) and Environmental Tobacco SmokeEnvironmental Tobacco Smoke

Effects of Environmental Tobacco Smoke Effects of Environmental Tobacco Smoke on Cardiovascular Diseaseon Cardiovascular Disease Effects of environmental Effects of environmental

tobacco smoketobacco smoke risk of heart diseaserisk of heart disease platelet and endothelial platelet and endothelial

functionfunction arterial stiffnessarterial stiffness atherosclerosisatherosclerosis oxidative stressoxidative stress inflammationinflammation– ↓↓ heart rate variabilityheart rate variability energy metabolismenergy metabolism infarct sizeinfarct size

American Heart Association. Scientific Position, Risk Factors and Coronary Heart Disease, 2005. http://americanheart.org. Accessed February 2007; Barnoya et al. Circulation. 2005; 111:2684-2698; http://www.istockphoto.com/file_closeup/abuse/smoking/tobacco_products/3383715_cigarette_burning.php?id=3383715. Accessed October 11, 2007.

Environmental Tobacco Smoke: Prevalence of Environmental Tobacco Smoke: Prevalence of Heart DiseaseHeart Disease

Adjusted for age, systolic blood pressure, diastolic blood pressure, total cholesterol, HDL cholesterol, FEV, height, preexisting CAD, body mass index, triglycerides, white cell count, diabetes, physical activity, alcohol intake, and social class. aLight active refers to men smoking 1-9 cigarettes a day. bHeavy passive refers to upper three quarters of cotinine concentration combined (0.8 to 14.0 ng/mL). cLight passive refers to lowest quarter of cotinine concentration among nonsmokers (0-0.07 ng/mL). Whincup et al. BMJ. 2004;329:200-205.

Exposure to environmental tobacco smoke increases the risk of Exposure to environmental tobacco smoke increases the risk of heart disease among nonsmokers by 30%heart disease among nonsmokers by 30%

Years of Follow up

Pro

po

rtio

n W

ith

Maj

or

CA

D

0 5 10 15 200

0.05

0.10

0.15

0.20

Light activea

Heavy passiveb

Light passivec

Environmental Tobacco Smoke: Environmental Tobacco Smoke: Platelet ActivationPlatelet Activation

ns=not significant. a Unless marked as “ns,” differences for each value between groups were statistically significant at a level of P<.05. Schmid et al. Thromb Res. 1996;81:451-460.

Nonsmokers Current Smokers

pg

/mL

a

36.8

34.8

32.8

30.8

28.8

26.8

24.8

22.81 2 3 4 5 12

11-dehydro-thromboxane B2

nsns

ns

Day

Min

/10°

Pla

tele

tsa

1 2 3 4 5 12

Malondialdehyde

Day

5.6

2.5

3.2

3.6

4.0

4.4

4.8

5.2

ns ns nsns

ns

ns

ns

ns

nsns

Environmental Tobacco Smoke: Environmental Tobacco Smoke: Vascular Endothelial DysfunctionVascular Endothelial Dysfunction

CFVR is a measure of endothelial function in the coronary circulation. Otsuka et al. JAMA. 2001;286:436-441.

Acute exposure to environmental tobacco smoke significantly reduces Acute exposure to environmental tobacco smoke significantly reduces mean coronary flow velocity reserve (CFVR) in nonsmokersmean coronary flow velocity reserve (CFVR) in nonsmokers

CF

VR

(M

ean

±S

D)

PP<.001<.001

2.0

2.5

3.0

3.5

4.0

4.5

5.0

5.5 Nonsmokers Current Smokers

Before Acute Exposure After Acute Exposure

Environmental Tobacco Smoke: Environmental Tobacco Smoke: Risk of Acute Myocardial Infarction (MI)Risk of Acute Myocardial Infarction (MI)

aThe ratio of the odds of development of disease in exposed persons to the odds of development of disease in nonexposed persons. Adjusted for age, sex, region, physical activity, and consumption of fruits, vegetables, and alcohol. Adapted from Teo et al. Lancet. 2006;368:647-658.

NonsmokersNonsmokers

Od

ds

Rat

io (

95%

CI)

Od

ds

Rat

io (

95%

CI)

aa

Environmental Tobacco Smoke Exposure (Hours per Week)Environmental Tobacco Smoke Exposure (Hours per Week)

NeverNever 1-71-7 8-148-14 15-2115-21 2222

44

22

11

0.750.75

Exposure to environmental tobacco smoke increased the risk Exposure to environmental tobacco smoke increased the risk of non-fatal acute MI in a graded mannerof non-fatal acute MI in a graded manner

Summary: Cardiovascular Disease and Summary: Cardiovascular Disease and Environmental Tobacco SmokeEnvironmental Tobacco Smoke

Exposure to environmental tobacco smoke increases Exposure to environmental tobacco smoke increases risk ofrisk of– Heart disease, by 30%Heart disease, by 30%– Acute myocardial infarction (MI)Acute myocardial infarction (MI)

Environmental tobacco smoke affects multiple factors Environmental tobacco smoke affects multiple factors associated with the development of coronary artery associated with the development of coronary artery disease, includingdisease, including– Platelet activationPlatelet activation– Vascular endothelial dysfunctionVascular endothelial dysfunction

Cardiovascular Benefits of Cardiovascular Benefits of Smoking CessationSmoking Cessation

Cardiovascular Benefits of Cessation: Cardiovascular Benefits of Cessation: FibrinogenFibrinogen After 2 weeks of cessation by formerly chronic smokers, both fibrinogen After 2 weeks of cessation by formerly chronic smokers, both fibrinogen

concentration and the rate of fibrinogen synthesis are reducedconcentration and the rate of fibrinogen synthesis are reduced

ASR=absolute rate of fibrinogen synthesis. aAbstention period of 2 weeks. Hunter et al. Clin Sci (Lond). 2001;100(4):459-465.

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

0

5

10

15

20

25

30

Fib

rin

og

en A

SR

mg

/kg

Fib

rin

og

en A

SR

mg

/kg

Pla

sma

Fib

rin

og

enP

lasm

a F

ibri

no

gen

Co

nce

ntr

atio

n (

g/L

)C

on

cen

trat

ion

(g

/L)

P<.001 P<.001

SmokingSmoking AbstentionAbstentionaa SmokingSmoking AbstentionAbstentionaa

16.1

24.12.49

3.06

6.1

7.0

0

1

2

3

4

5

6

7

8

Cardiovascular Benefits of Cessation: Cardiovascular Benefits of Cessation: White Blood CellsWhite Blood Cells

aAbstention period of 17 weeks.Eliasson et al. Nicotine Tob Res. 2001;3(3):249-255.

AbstentionaSmoking

Wh

ite

Blo

od

Cel

ls (

×10

9 /l) P<.026

0.420.33

0.0

0.2

0.4

0.6

0.8

1.0

1.321.16

0.0

0.5

1.0

1.5

2.0

2.5

3.0

Cardiovascular Benefits of Cessation: Improved Cardiovascular Benefits of Cessation: Improved Lipid ProfileLipid Profile

HDL=high-density lipoprotein; LDL=low-density lipoprotein. aAbstention period of 17 weeks.Eliasson et al. Nicotine Tob Res. 2001;3(3):249-255.

P<.001

HD

L (

mm

ol/L

) 3.523.78

0.0

1.0

2.0

3.0

4.0

5.0

LD

L (

mm

ol/L

)

Smoking Abstentiona

Smoking Abstentiona

HD

L/L

DL

Rat

io

P<.015

P<.001

Smoking Abstentiona

7276

0

20

40

60

80

100

120

Cardiovascular Benefits of Cessation: Cardiovascular Benefits of Cessation: Hemodynamic ProfileHemodynamic Profile Smoking cessation is associated with an improvement in Smoking cessation is associated with an improvement in

hemodynamic parameters.hemodynamic parameters.

a Abstention period of 6 months. Oren et al. Angiology. 2006;57(5):564-568.

8790

0

20

40

60

80

100

120

Hea

rt R

ate

(Bea

ts/m

in)

P<.05

Mea

n A

rter

ial

Pre

ssu

re (

mm

Hg

)

Smoking

P<.05

SmokingAbstentiona Abstentiona

0

10

20

30

40

50

60

70

80

90

Au

gm

enta

tio

n In

dex

(%

)b

Cardiovascular Benefits of Cessation: Cardiovascular Benefits of Cessation: Hemodynamic Profile (cont’d)Hemodynamic Profile (cont’d) Smoking cessation is associated with an improvement in arterial Smoking cessation is associated with an improvement in arterial

compliancecompliance

aProvides an assessment of small arteriolar compliance. bThe amplitude of the reflected wave depends on the stiffness of the small vessels and large arteries and thus provides a measure of systolic arterial stiffness.cAbstention period of 6 months. Oren et al. Angiology. 2006;57(5):564-568.

6.3

5.1

0

2

4

6

8

10

Osc

illat

ory

Co

mp

lian

ce

(mL

/mm

Hg

× 1

00)a

P<.01

P<.05

Smoking Abstentionc Smoking Abstentionc

63.1

50.6

Cardiovascular Benefits of Cessation: Cardiovascular Benefits of Cessation: Platelet EffectsPlatelet Effects Smoking is associated with reduced platelet volume and enhanced platelet Smoking is associated with reduced platelet volume and enhanced platelet

cAMPcAMPcc response to stimulation of adenylate cyclase with prostaglandin E response to stimulation of adenylate cyclase with prostaglandin E11

aPGE=prostaglandin E1; bMPV=mean platelet volume; ccAMP= cyclic adenosine monophosphate.Terres et al. Am J Med. 1994;97:242-249.

0 1 2 1 4 8 9 1 4 8 9 12Weeks

4

8

10

12

6

cAM

P A

fter P

GE

(nm

ol/L

) (95

% C

I)a

P=.02

MPV

(fL)

(95%

CI)b

Weeks

P<.001

8.2

8.4

8.6

9.0

8.8

0 1 2 1 4 8 9 1 4 8 9 12

NicotineChewing

Gum

Smoking Nonsmoking/Nonchewing

Smoking NicotineChewing

Gum

Nonsmoking/Nonchewing

Cardiovascular Benefits of Cessation: Cardiovascular Benefits of Cessation: Platelet Effects (cont’d)Platelet Effects (cont’d)

aQuit smoking for 28 days. bResumed smoking after quitting for 14 days.ADP=adenosine diphosphate. ADP is a platelet aggregation agonist.Morita et al. J Am Coll Cardiol. 2005;45:589-594.

Smoking abstinence is associated with reduced platelet Smoking abstinence is associated with reduced platelet aggregabilityaggregability

ADP=5.0 µmol/L

Group Aa Group Bb

Pla

tele

t A

gg

reg

atio

n (

%)

0

20

60

100

40

80

Time (Days)

0 7 14 21 28

NS

P<.01

NS

NS

P<.01

Cardiovascular Benefits of Cessation: Cardiovascular Benefits of Cessation: Reduced Risk of Arrhythmic DeathReduced Risk of Arrhythmic Death Cessation of cigarette smoking is associated with a reduction in arrhythmic Cessation of cigarette smoking is associated with a reduction in arrhythmic

death for patients with post-myocardial infarction left ventricular dysfunctiondeath for patients with post-myocardial infarction left ventricular dysfunction

Peters et al. J Am Coll Cardiol. 1995;26(5):1287-1292.

P=.040

Survival in Years

Su

rviv

al (

%)

0

20

40

60

80

100

0 2 31

Ex-smokers

Smokers

Cardiovascular Benefits of Cessation: Cardiovascular Benefits of Cessation: Reduced Risk of Acute Myocardial Reduced Risk of Acute Myocardial Infarction (MI)Infarction (MI)

aThe ratio of the odds of development of disease in exposed persons to the odds of development of disease in nonexposed persons. Adjusted for sex, region, diet, alcohol, physical activity, consumption of fruits, vegetables, and alcohol.Adapted from Teo. Lancet. 2006;368:647-658.

PP<.0001<.0001

CurrentCurrent >1-3>1-3 >5-10>5-10 >10-15>10-15 2020

Ex-smokers (Years Since Cessation)Ex-smokers (Years Since Cessation)

>3-5>3-5 >15-20>15-20

Od

ds

Rat

io (

95%

CI)

Od

ds

Rat

io (

95%

CI)

aa

44

22

11

Cardiovascular Benefits of Citywide Smoke-Cardiovascular Benefits of Citywide Smoke-Free Ordinance: Reduced Incidence of Acute Free Ordinance: Reduced Incidence of Acute MIMI

Bartecchi et al. Circulation. 2006;114:1490-1496.

27% reduction in the incidence of acute myocardial infarction (MI) after 27% reduction in the incidence of acute myocardial infarction (MI) after implementation of a smoke-free ordinance in Pueblo City, Coloradoimplementation of a smoke-free ordinance in Pueblo City, Colorado

AM

I C

ou

nts

per

100

,000

Per

son

-Yea

rs

257

119

187

116

0

50

100

150

200

250

300

Pueblo City El Paso County

Preordinance Postordinance

P<.001

Cardiovascular Benefits of Cessation: Reduced Cardiovascular Benefits of Cessation: Reduced Risk of Recurrent Cardiac ArrestRisk of Recurrent Cardiac Arrest The risk for recurrent cardiac arrest is lower among those who quit smoking The risk for recurrent cardiac arrest is lower among those who quit smoking

than among continuing smokersthan among continuing smokers

aAbstention period of 3 years. Hallstrom et al. N Engl J Med. 1986;314:271-275.

27

19

0

5

10

15

20

25

30

Current Smokers Ex-smokersa

Occ

urr

ence

at

3 Y

ears

(%

)

P=.038

Recurrent Cardiac Arrest

Cardiovascular Benefits of Cessation: Reduced Cardiovascular Benefits of Cessation: Reduced Mortality After Percutaneous Coronary Mortality After Percutaneous Coronary RevascularizationRevascularization Current smokers had a significantly greater risk of overall mortality after Current smokers had a significantly greater risk of overall mortality after

percutaneous coronary revascularizationpercutaneous coronary revascularization

Su

rviv

al (

%)

100

80

60

40

20

00 2 3 4 5 6 7 8 9 10 11 12

Years After Index Procedure

Hasdai. N Engl J Med. 1997;336(11):755-761.

Quitters

Persistent Smokers

Cardiovascular Benefits of Cessation: Reduced Cardiovascular Benefits of Cessation: Reduced Mortality After Coronary Artery Bypass GraftMortality After Coronary Artery Bypass Graft

Estimated survival benefit associated with smoking cessation Estimated survival benefit associated with smoking cessation increased from 3% at 5 years to 10% at 10 years and 15% at 15 yearsincreased from 3% at 5 years to 10% at 10 years and 15% at 15 years

Adapted from van Domburg et al. J Am Coll Cardiol. 2000;36(3):878-883.

Pro

bab

ilit

y o

f S

urv

ival

(%

)

0 5 10 15 20

Years

PP<.0001 (Ex-smokers vs <.0001 (Ex-smokers vs Current Smokers)Current Smokers)

Nonsmokers

Persistent Smokers

100

80

60

40

20

0

Quitters

Cardiovascular Benefits of Cessation: Cardiovascular Benefits of Cessation: Reduced Progression of Peripheral Vascular Reduced Progression of Peripheral Vascular DiseaseDisease

Jonason et al. Acta Med Scand. 1987;221:253-260.

Years

Res

t P

ain

, C

um

ula

tive

(%

)

30

20

10

0

P=.049

2 71 6543

Abstention

Smoking

Cardiovascular Benefits of Cessation: Cardiovascular Benefits of Cessation: Reduced Risk of StrokeReduced Risk of Stroke

aThe probability of an event (developing a disease) occurring in exposed people compared with the probability of the event in nonexposed people. Adjusted for age and treatment assignment.Robbins et al. Ann Intern Med. 1994;120(6):458-462.

1.0

2.5

2.0

1.2

0

1

2

3

4

Nonsmokers Ex-smokers CurrentSmokers

(<20 cig/d)

CurrentSmokers

(≥20 cig/d)

Rel

ativ

e R

isk

(95%

CI)

a

P for trend <.0001

Cardiovascular Benefits of Smoking CessationCardiovascular Benefits of Smoking Cessation

Short-term BenefitsShort-term Benefits fibrinogen concentrationfibrinogen concentration rate of fibrinogen synthesisrate of fibrinogen synthesis WBCsWBCs Improved HDL/LDL ratioImproved HDL/LDL ratio risk of strokerisk of stroke HDL; decreased LDLHDL; decreased LDL arterial pressurearterial pressure HRHR Improved arterial complianceImproved arterial compliance risk of arrhythmic death after MIrisk of arrhythmic death after MI platelet volumeplatelet volume Enhanced platelet cAMP response to Enhanced platelet cAMP response to

stimulation of ADP with prostaglandin E1stimulation of ADP with prostaglandin E1 smoking-induced platelet aggregabilitysmoking-induced platelet aggregability

Long-term BenefitsLong-term Benefits Reduced risk ofReduced risk of

– Stroke Stroke – Repeat CABG Repeat CABG – Recurrent coronary events Recurrent coronary events

after MIafter MI– Arrhythmic death after MIArrhythmic death after MI– Secondary CVD events Secondary CVD events – Revascularization procedure Revascularization procedure

after CABGafter CABG Reduced Reduced

– Mortality after CABGMortality after CABG– Mortality after PTCAMortality after PTCA– Levels of inflammatory Levels of inflammatory

markers associated with markers associated with progression of CVD progression of CVD (C-reactive protein, WBC, and (C-reactive protein, WBC, and fibrinogen)fibrinogen)

Twardella et al. Eur Heart J. 2004;25:2101-2108; Morita et al. J Am Coll Cardiol. 2005;45:589-594; Oren et al. Angiology. 2006;57:564-568; Terres et al. Am J Med. 1994; 97:242-249; Nilsson et al. J Int Med. 1996; 240:189-194; Peters et al. J Am Coll Cardiol. 1995;26:1287-1292; Rea et al. Ann Intern Med. 2002;137: 494-500; Hasdai et al. N Engl J Med. 1997;336:755-761; van Domburg et al. J Am Coll Cardiol. 2000; 36:878-883; Bakhru et al. PLoS Med. 2005;2:e160; Eliasson et al. Nicotine Tob Res. 2001;3 :249-255; Hunter et al . Clin Sci. 2001;100 :459-465; Wannamethee et al. JAMA. 1995;274:155-160.