Summary of Observational Studies

In a meta-analysis of cohort and case-control studies of cigarette smoking and stroke
(Shinton and Beevers 1989), the overall relative risk of stroke among former smokers
was 1.17 compared with never smokers (95-percent CI, 1.05-1.30). This estimate is
based on a summary of 18 relative risks from 13 studies that separately identified former
smokers (Kahn 1966: Doll and Peto 1976; Abbottet al. 1986; Colditzet al. 1988: Ostfeld
et al. 1974; Kono et al. 1985; Khaw et al. 1984; Vessey. Lawless, Yeates 1984: Bell
and Symon 1979; Bell and Ambrose 1982; Bonita et al. 1986; Bonita 1986; Taha, Ball.
I!lingworth 1982). As observed for the relation between current smoking and stroke.
the risk among former smokers was greater when the analysis was repeated using only
those studies with stroke occurring before age 75 (RR=1.47. 95-percent CI. 1.15-1.88
compared with never smokers). By comparison. the relative risks for current smokers
were 2.9 for those younger than 55 years and 1.8 for persons aged 55 to 74 years. Thus,
although a modest elevation in risk persisted among younger former smokers, this
relative risk was substantially less than that which was observed among current
smokers.

Intervention Studies

Intervention trials described above provide little direct evidence relating to change
in risk of stroke after smoking cessation. Only the trial of smoking cessation conducted
among 1.445 British men used a single intervention (Rose et al. 1982). During 10 years
of followup, five men in the normal care group died because of stroke, and seven men
in the intervention group died because of stroke. The small numbers in each group and
the small difference in smoking cessation rates between the intervention and control
groups limit any conclusion regarding the impact of smoking cessation in this popula-
tion.

Other intervention studies have included management of hypertension and
cholesterol as well as smoking cessation programs. As discussed under randomized
trials of smoking cessation and CHD, these multiple interventions make drawing
conclusions difficult regarding the relation between smoking cessation and risk of
stroke (Steinbach et al. 1984; Wilhelmsen et al. 1986; MRFIT Research Group 1982.
1986; Salonen, Puska, Mustaniemi 1979; Hjermann 1980; Holme 1982).

In a nonrandomized intervention, Rogers and colleagues (1985) measured changes
in cerebral artery blood flow among volunteers who were encouraged to abstain from
cigarettes. Cerebral perfusion was improved after smoking abstinence.

Influence of Prior Levels of Smoking

Using data from the followup of 248,046 U.S. veterans monitored for 15 years, Rogot
and Murray (1980) reported the mortality ratio for stroke among former cigarette
smokers who stopped smoking for reasons other than a physician’s orders according to
the level of prior cigarette smoking. Based on 1,279 strokes among past smokers, the
mortality ratio for stroke among former smokers relative to never smokers increased
with higher previous daily cigarette consumption from 0.94 for those smoking less than
10 cigarettes per day to 1.34 for those smoking 40 cigarettes or more per day compared
with never smokers (Figure 7). Data from ACS CPS-II also address this relationship
(Table 8). Within each level of previous smoking, the risk of stroke was clearly lower
for former smokers than for continuing smokers, except among men who smoked 21
cigarettes or more per day. Other studies have had too few former smokers to classify
them according to previous number of cigarettes smoked.

 

 

 

 

STROKE (330-334)

<10 cig/day 10-20 cig/day 21-39cig/day >40 cig/day

Ex-Smokers Wi Current Smokers

FIGURE 7.—Mortality ratios for stroke for current smokers and ex-smokers
compared with never smokers, by daily cigarette consumption,
US Veterans Study, 1954-69

SOURCE: Adapted trom Rogot and Murray (1980).

Effect of Duration of Abstinence

The relation between duration of abstinence and risk of stroke has been addressed in
only a few studies. In a case-control study that included 145 former smokers who
suffered stroke, Donnan and coworkers (1989) observed that the relative risk of stroke
declined monotonically over the 10 years following quitting: at the end of 10 years. a
significant excess risk of stroke was still evident.

Using 5-year intervals. Rogot and Murray (1980) reported the mortality ratios for
those who had abstained. Assuming that an individual classified as a former smoker at
the beginning of the study would remain a former smoker throughout the 15 years of
TABLE 8.—Prospective cohort studies of smoking cessation and risk of stroke

 

Relative risk compared with never smokers"

 

 

Cases among Former Current
Reference Population Followup former smokers Outcome smokers smokers
Ostfeld et al. (1974) 2,748 Cook County, IL 3yr 23 All strokes oo? 1-9 cipfday: 1.29

Nomura et al. (1974)

Doll and Peto (1976)

Okada et al. (1976)

residents receiving old age
assistunce aged 65-74

47.423 Washington County,

MD residents

British physicians: 34,440
men

4.186 Japanese

2 yr morbidity

20 yr

27 (men)

X (women)

NR

NR

Thrombosis
Hemorrhage
Undifferentiated
Total

Thrombosis
Hemorrhage
Undifferentiated
Total

Cerebral thrombosis
mortality

Cerebrovascular
attacks

tO 19 cig/day: 0.85
220 cigAlay: O.81

1.a3e 0.79
0.79 0.86
1.00 1.30
0.97 0.90
1.08 lid
2.00 091
Ld 0.36
1.26 0.92
1.22 1.24

Relative risk of cerebral hemorrhage
in nonsmokers was lower than in
smokers or ex-smokers, but the
difference was not statistically
Significant
he

TABLE 8.—Continued

 

Relative risk compared with never smokers”

 

 

Cases among Former Current
Reference Population Followup former smokers Outcome smokers smokers
Doll etal. (1980) British physicians: 6,194 22 yr NR Death due to cerebral 1.18 I-14 cig/day: 0.93
women thrombosis 14-24 cig/day: 0.45
225 cig/day: 0.19
Rogot and Murray US veterans: 248,046 men 15 yr 1,279 Stroke ICD 330-343 1.02 1.32
(1980) (7th revision)
Fuller et al. (1983) Whitehall civil servants: LO yr 34 Stroke mortality 1.52 1-9 cig/day: 1.0°
[8.403 men aged 40-64 10-19 cig/day: 2.0
220 cig/day: 2.3
Vessey. Lawless, 17,000 UK women aged 10-16 yr 2 Subarachnoid 2.3 3.0
Yeates (1984) 25-39 4 Nonhemorrhagic 1.3 14
Abbott et al. (1986) Honolulu Heart Study: 7,895 12 yr, tl Thromboembolic 1.6 (0.7-3.8) 3.00
men of Japanese origin: 658 6 yr 3 Hemorrhagic 1.8 (0.4-9.0) 6.10
smokers who quit in first 6 yr Total 1.5 (1.0-2.3) 3.50
Welin et al. (1987) 789 men living in Gothenburg, 18.5 yr: NR Excluded subarachnoid 1.18" 1.67
678 examined I yr hemorrhage
Carstensen, 25,159 Swedes 16 yr 124 Cerebrovascular mortality 1.10 1-7 g/day: 0.9
Pershagen, Eklund ICD 430-438 8-15 g/day: 0.9
(1987) >IS g/day: 1.4
TABLE 8.—Continued

 

. . a
Relative risk compared with never smokers

 

 

; Cases among Former Current
Reterence Population Followup former smokers Outcome smokers smokers
Wolf et al. (1988) Framingham Study: 4,255 26 yr N/A Stroke and transient Risk significantly Men:
men and women ischemic attack lower than that of 1.42 stroke
current smokers 1.56 brain
infarction
Women:
1.61 stroke
1.86 brain
infarcuion
Colditz etal. (1988) Nurses Health Study: 118.539 8 yr 65 Subarachnoid 3.0 (1.3-6.6) l-l4cig/day: 4.3
US women aged 30-55 hemorrhage 15-24 cip/day: 5.1
225 cig/day: 10.3
Thromboembolic 1.3 (0.7-6.6) l-t4cig/day: 1.8
stroke 15-24 cig/day: 3.2
225 cig/day: 3.1
Total stroke LS (1.12.2) 1-l4cig/day: 2.5
15-24 cig/day: 2.9
225 cighlay: 3.8
US DHHS (1989) ACS CPS-I (25-State Study) 6 yr (1959-65) NR Men"

1.79 (1.55 2.08)"
145 (1.02 1.30)"

35 64 yr: 1.02 (0.83 1.25)"
265 yr: O93 (O80 LOX
TABLE 8.—Continued

 

Relative risk compared with never smokers"

 

 

 

Cases among Former Current
Reference Population Followup former smokers Outcome smokers smokers
. Men <21 cig/day
ACS (unpublished ACS CPS-H(SO0-State Study) 4d yr (1982-86) NR Mortality due to
tabulations} cerebrovascular Quit <] yr 3.94 2.43
disease yr dtl

3-S yr $.55
6-10 yr L.64
H1-15 yr 0.62

216 yr 0.72

Men 221 cig/day

 

Quit <1 yr 0.37 2.07
l-2 yr b.43
3-5 yr 1.39
6-10 yr 2.27
TH) US yr 2.34
>l6yr 1.92

Women <20) cig/day

 

Quit<! ye NR 1.77
I-2 yr 1.92
3-5 yr 0.79
6-10 yr 0.59
1-15 yr $.23
2l6yr 0.93
TABLE 8.—Continued

+ . . a
Relative risk compared with never smokers

 

 

Cases among Former Current
Reference Population Followup former smokers Outcome smokers smokers
ACS (unpublished Women 220 cig/day
tabulations) Quit <P yr 0.29 2.33
(continued) | 2yr 0.51
3 Syr 0.71

6-10 yr O84
[1-15 vr 0.23
2l6yr 0.73

NOTE: N/A=not applicable: ACS CPS-E and -H=American Cancer Society Cancer Prevention Studies Land Ik NR=not reported: ICD=International Classification of Disease
“95% confidence interval shown in parentheses when available.
h . . .
Relative risk calculated from data presented in original paper.
“Relative risk reported by Shinton and Beevers (1989)
{ . .
“Data for women former smokers not presented separately.
“Excluding those with a history of cancer, heart disease, or stroke at enrollment.
followup, these investigators reported mortality ratios close to 1.0 for all durations
except for S to 9 years after quitting.

Based on 26 years of studying 4.255 men and women in the Framingham Study (Wolf
etal. 1988), the risk of stroke among persons who stopped was significantly lower than
that among persons who continued to smoke cigarettes. Furthermore. persons who quit
smoking developed stroke at the rate of never smokers soon after discontinuing
cigarette smoking (Figure 8). Wolf and coworkers (1988) estimated that the risk of
stroke among smokers had decreased significantly 2 years after quitting and reverted
to the level of never smokers within 5 years. These results persisted after controlling
for age. blood pressure. serum cholestrol level, relative weight, left ventricular hyper-
trophy on electrocardiogram, and blood glucose level. Thus. the reduction in risk after
smoking cessation is not attributable to differences in other risk factors for stroke
between those who quit and those who continue to smoke.

In the Nurses Health Study (Colditz et al. 1988), a lower risk of stroke was observed
with increasing time from cessation. Compared with the risk among never smokers.
the relative risk was 2.6 among women who had stopped for less than 2 years
(95-percent Cl. 1.44.7). However. among women who had stopped for 2 years or
more, the relative risk was reduced to 1.4 (95-percent CI. 1.0-2.0).. Women currently
smoking 15 to 24 cigarettes per day had a relative risk of 2.9 compared with never
smokers. Again, the elevation of the relative risk during the first 2 years after cessation
is consistent with high recidivism among these women.

Prospective data from ACS CPS-II showed that among men who quit smoking. the
risk of stroke returned to that of never smokers after 11 years or more of smoking
abstinence for those originally smoking tewer than 21 cigarettes per day. However. for
men who previously smoked 2] cigarettes or more per day. the risk among former
smokers did not return to the level of never smokers, even after 16 years or more of
cessation. Among women who quit. the rate of decrease was much more rapid: by 3 to
5 years after cessation, the risk of stroke was similar to that of never smokers (Table
8).

Oral Contraceptives and Smoking Cessation

In two studies the risk of subarachnoid hemorrhage was augmented among cigarette
smokers who also take oral contraceptives (Petitti and Wingerd 1978: Collaborative
Group for the Study of Stroke in Young Women 1975). In the Collaborative Group
Study of stroke among young women (1975), the category of former smokers was not
clearly detined: rather, a group of “once regular smokers” was compared with “never
regular smokers.” In this study there was no association between current smoking or
former smoking and risk of thrombotic stroke. Overall. the relative risk for hemorrhagic
stroke was 1.8 among once reguliur smokers and 3.3 among current smokers. Within
the group of once regular smokers. women currently using oral contraceptives had
approximately twice the risk compared with women not using oral contraceptives. The
Royal College of General Practitoners study of oral contraceptives did not separate
former smokers from never smokers (Layde. Beral, Kay 1981). Hence, data to address
the relationship among oral contraceptives. smoking cessation, and risk of subarachnoid

258
100 4

 

 

 

 

£
° 90°
“A
6
@
@
we
x 80"
70 T T T T r v =
0 5 10 15 20 5 10 15 20

Years of Follow-up

FIGURE 8.—Survival free of stroke in cigarette smokers (dotted line), never

smokers (solid line), and former smokers (dashed line), aged 60,
using Cox proportional hazard regression model, among men and
women

SOURCE: Wolf et al. (19%),
hemorrhage are not available from that study. Because oral contraceptive preparations
used today provide substantially lower doses, the risk of cardiovascular disease as-
sociated with their use and their interaction with cigarette smoking may be different
than observed for the early high-dose preparations.

Effect of Smoking Cessation After Stroke

In contrast with CHD, in which the focus after MI is prevention of recurrent disease.
the center of attention after a major cerebrovascular event is rehabilitation. For CHD.
substantial evidence shows the benefits of abstaining from smoking after onset of CHD.
Comparable data are not available on the benefits of abstinence after stroke.

Summary

Risk of stroke resulting from occlusion of the cerebral arteries and from subarachnoid
hemorrhage is increased approximately twofold to fourfold among current smokers
compared with never smokers. After cessation, the excess risk decreases steadily. In
some studies, the risk of stroke among former smokers becomes indistinguishable from
that of never smokers within 5 years: in other studies. this decrease did not occur until
after 10 years or more of smoking abstinence. The reduced risk of stroke among persons
who stop smoking is independent of the amount previously smoked and other known
risk factors for stroke. Similar reductions in risk of stroke after cessation are seen
among men and women, but tew data are available for minority populations.

CONCLUSIONS

1. Compared with continued smoking, smoking cessation substantially reduces risk of
coronary heart disease (CHD) among men and women of all ages.

2. The excess risk of CHD caused by smoking is reduced by about half after | year of
smoking abstinence and then declines gradually. After 15 years of abstinence, the
risk of CHD is similar to that of persons who have never smoked.

3. Among persons with diagnosed CHD. smoking cessation markedly reduces the risk
of recurrent infarction and cardiovascular death. [In many studies. this reduction in
risk of recurrence or premature death hits been S50 percent or more.

4. Smoking cessation substantially reduces the risk of peripheral artery occlusive

disease compared with continued smoking.

. Among patients with peripheral artery disease. smoking cessation improves exercise

tolerance, reduces the risk of amputation after peripheral artery surgery. and

In

increases overall survival.

6. Smoking cessation reduces the risk of both ischemic stroke and subarachnoid
hemorrhage compared with continued smoking. After smoking cessation, the risk
of stroke returns to the level of never smokers: in some studies this has occurred
within 5 years. but in others as long as [5 years of abstinence were required.

260
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CHAPTER 7
SMOKING CESSATION AND
NONMALIGNANT RESPIRATORY DISEASES

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