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156
SECTION 4. CEREBROVASCULAR
DISEASE

157
Introduction

Death rates from stroke have been declining in developed coun-
tries since the 1920s (28). Between 1968 and 1975 there was a sharp
decline in the age-adjusted mortality rates from coronary heart
disease, cerebrovascular diseases, and all major cardiovascular
diseases among U.S. white and nonwhite males and females (50). As
shown in Table 1, the decrease is close to 33 percent for stroke.

Additional major reductions in disability and death from stroke
can come largely from preventive measures, not from further
innovations in treatment of the completed catastrophe. Formulation
of a preventive program is greatly aided by an understanding of the
epidemiology of cerebrovascular disease, including the chain of
circumstances leading to its occurrence, the identity of vulnerable
subgroups of the population, the existence of modifiable predisposing
factors, and the natural history of the disease.

Magnitude of the Problem

Cerebrovascular diseases, both ischemic and hemorrhagic, are a
public health problem of major proportions. They constitute the
third leading cause of death, after coronary heart disease and cancer,
and are responsible for 9 percent of all deaths in the United States
(33). There are about 1.8 million stroke victims in the United States,
and about a half-million new events occur each year; there are
approximately 200,000 deaths annually in the United States from
strokes. In the Framingham study it was estimated that the chances
of suffering a stroke before age 70 are 1 in 20. The incidence was
found to double in each successive decade after age 45. Although
stroke incidence becomes substantial only after age 65, 20 percent of
strokes occur before that age. In men, the average annual incidence
of atherothrombotic brain infarction is only one-third that of
myocardial infarction, with stroke incidence lagging behind myocar-
dial infarction by more than 10 years. In women, on the other hand,
brain infarction incidence and myocardial infarction incidence are
virtually identical (56). The reasons that brain infarction is manifest-
ed later in life than CHD in men and exhibits little male predomi-
nance are unclear. In the United States, stroke mortality is higher
among blacks than among whites, and the difference decreases with

age.

The Stroke Entity

There are three major specific forms of cerebrovascular diseases:
(1) cerebral insufficiency associated with transient blood flow
deficiencies; (2) cerebral infarction caused either by the blocking of a
vessel by an embolism or by thrombosis; and (3) cerebral hemor-
rhage, including parenchymal and subarachnoid. The terms “stroke”

159
TABLE 1.—Percentage of change in mortality rates of
causes of death in persons aged 35 to 74, by
sex and color, United States, 1968-1976

 

Percentage of change

 

 

White White Nonwhite Nonwhite
Cause of death men women men women All
Coronary heart disease ~21.0 -26.5 ~30.7 -39.1 -24.3
Cerebrovascular diseases 30.6 ~30.4 43.7 AT ~32.7
Major cardiovascular diseases -20.9 -26.1 -33.2 40.7 -24.6
All causes ~-15.3 -16.4 -24.8 32.7 -17.3

 

SOURCE: Stamler (50).

and “cerebral vascular accident” are nonspecific; they refer to a
variety of clinical entities and are usually used in reference to
syndromes accompanying ischemic or hemorrhagic lesions.

The underlying process of a stroke may be an atheroma (i.e., fatty
deposit in the inner lining of an artery wall), thrombosis, embolism,
a bleeding disorder, a developmental anomaly, an aneurysm, inflam-
mation, failure of flow, or increased blood viscosity. The chief causes
of cerebral ischemia are atherothrombosis and embolism. Intracrani-
al hemorrhage is generally due to hypertensive intracerebral
hemorrhage, rupture of a saccular aneurysm, or bleeding from an
arteriovenous malformation. A cerebral embolism usually originates
in the heart, particularly when atrial fibrillation, rheumatic valvu-
lar deformity, myocardial infarction with a mural thrombus, or a
valve prosthesis is present; it may also arise from ulcerated
atheroma in the carotid, vertebrobasilar, or middle cerebral arteries.
The main trunk of the middle cerebral artery and its branches are
the most common sites for the formation of intracranial thrombosis.

The reliability of stroke diagnoses and case ascertainment in
diverse populations has presented problems for epidemiological and
clinical research. With the fairly recent development of new
technology such as computer-assisted tomography, however, the
accuracy and the quality of differential diagnosis as to type of stroke
are improving. It is unlikely that any single etiology or set of risk
factors applies equally to all types of stroke. Atherothrombotic brain
infarction is the most common variety of stroke, accounting for
about 59 percent of the total number of strokes in the Framingham
population (56).

Cardiovascular Risk Factors

Since the underlying pathologic features of atherosclerosis in the
cerebral, cardiac, and peripheral circulation are virtually identical,

160
it is not unexpected to find that they share a number of precursors.
Although some significant differences in their impact exist, there are
a number of modifiable risk factors common to brain and myocardial
infarction (22). In fact, when five major cardiovascular risk factors
(systolic blood pressure, serum cholesterol, glucose intolerance,
cigarette smoking, and electrocardiogram-left ventricular hypertro-
phy (ECG-LVH)) are considered jointly as a cardiovascular risk
profile, they are actually more highly predictive of brain infarction
than of coronary heart disease (24). The top decile of multivariate
risk using this profile identifies half the strokes evolving in the
Framingham population, compared with only 25 percent of the
coronary events (22). However, for cerebrovascular disease, systolic
blood pressure and ECG-LVH were the chief determinants of this
multivariate predictive capacity. In addition to these risk predictors,
various cardiac impairments such as coronary heart disease, cardiac
failure, and atrial fibrillation are major predisposing factors (55).
Cigarette smoking, which is a major predictor for coronary heart
disease, has been less consistently predictive for cerebrovascular
disease; but nevertheless appears to play a significant role among
men at younger ages.

Hypertension

A consistent finding in epidemiologic studies is that elevated blood
pressure is the most important risk factor for stroke. This seems to
apply for virtually all varieties of stroke (56). It is the key risk factor
for intracerebral hemorrhage, occlusive cerebral vascular disease,
and perhaps subarachnoid hemorrhage (28). About 50 to 60 percent
of strokes occur in the 20 percent of the population with definite
hypertension. Hypertension predisposes powerfully to stroke at all
ages and in both sexes, and even mild elevations in blood pressure
double the risk. The stroke risk for isolated systolic hypertension is
substantial, and the exclusive use of diastolic pressure to judge the
risk in the elderly with systolic hypertension can be misleading. No
component of blood pressure, including the pulse pressure, mean
arterial pressure, or diastolic pressure, is more closely related to
stroke incidence than systolic pressure (25). Also, lability of the
pressure has not been shown to reduce the risk, and it is not safe to
use the lowest pressure recorded to determine whether treatment is
indicated.

Blood Lipids

Lipids and their lipoprotein vehicles, closely linked to coronary
disease incidence, are of uncertain importance for stroke. Neither
cholesterol nor triglyceride levels have any predictive value beyond
age 55, when strokes are common, and partition of the serum total
cholesterol into its atherogenic low density lipoprotein (LDL) and

161
protective high density lipoprotein (HDL) components does not
clarify the role of cholesterol in stroke as it does for coronary heart
disease in advanced age (11). In women there is actually a paradoxi-
cal, strong negative association of brain infarction incidence with
LDL cholesterol. This inverse relationship to atherogenic cholesterol
has also been noted in Japanese men and for intracerebral hemor-
rhage (79). Hence, further clarification is needed.

Glucose

Atherothrombotic brain infarction incidence is increased threefold
in diabetics. In contrast to coronary heart disease, the impact of
impaired glucose tolerance does not diminish with advancing age
and is not greater for women than for men. The effect of diabetes
mellitus is independent of other risk factors, but is greatly influ-
enced by coexistent hypertension or cardiac disease (23).

Cardiac Disease

Even if asymptomatic, cardiac changes such as ECG-LVH, cardiac
enlargement on X-ray, atrial fibrillation, coronary disease, cardiac
failure, or rheumatic heart disease powerfully predispose to the
occurrence of strokes. ECG-LVH is the most powerful ECG predictor.
Atrial fibrillation, chronic as well as intermittent, increases stroke
risk sixfold, and when accompanied by rheumatic heart disease,
seventeenfold (55). Although each contributes independently to risk,
coexistent hypertension further augments the risk associated with
any cardiac impairment.

Environmental Factors

Few modifiable environmental contributors to stroke incidence
have been convincingly demonstrated. The demonstrated association
of obesity with stroke incidence appears to derive mainly from the
higher blood pressure and glucose intolerance that it promotes.
Physical activity is weakly and inconsistently related to stroke
incidence (55). The apparent influence of coffee intake disappears on
adjustment for coexistent alcohol and cigarette use. Alcohol seems to
be associated with an increased risk of stroke in some studies,
possibly because of higher blood pressure in alcohol users.

Cigarette Smoking

The contribution of cigarette smoking to the incidence of stroke
may vary depending on the type of stroke or clinical manifestation of
cerebrovascular disease. The evidence for such a relationship

suggests that smoking is more strongly associated with premature
(i.e., before age 55) and nonfatal strokes than with fatal strokes (22).

162
With 16 years of followup data on 293,000 insured US. veterans,
Rogot and Murray (43) reported that 653 excess stroke deaths were
associated with cigarette smoking, producing a mortality ratio of
1.47, Earlier, with 8.5 years of followup, Kahn (21) had found stroke
mortality to be 1.4 times higher in smokers and rates to increase
with amount smoked. In the more recent study, a slight dose-
response relationship was found for both current and ex-smokers,
with mortality ratios lower among former smokers than among
current smokers. Mortality ratios for stroke were near unity for
smokers of only cigars or pipes—1.07 and 0.99, respectively (43). A
study of 54,460 men employed in British industries revealed no
relationship between the cigarette habit and stroke mortality over 3
years, but demonstrated a threefold excess coronary mortality (3).

Kuller (28), in a review of the epidemiology of stroke, concluded
that there was no consistent evidence of a relationship of cigarette
smoking to stroke in several population and case-control studies.
Data after 24 years of followup in the Framingham study showed no
overall statistically significant relationship between the incidence of
atherothrombotic brain infarction (ABI) and cigarette smoking
among males. The stroke incidence was lower in nonsmoking males
only between the ages of 45 and 54, and no clear dose-response was
evident (56). In a comparison of stroke prevalence—not specified as
to type—among Japanese in Japan, Hawaii, and California, prelimi-
nary analyses revealed positive correlations between stroke and
increased blood pressure, ECG-LVH, and cigarette smoking for all
ages (20). Paffenbarger et al. (37) found no relationship between
cigarette smoking and stroke in a 22-year followup of 3,686 long-
shoremen.

In an earlier study of chronic diseases among male former
students at Harvard, Paffenbarger and Wing (38) noted a slight
excess of nonfatal stroke among those who had smoked during
college. They also found that hypertension, overweight, and short
stature were predisposing characteristics for stroke in later life. The
data must be interpreted with some caution, however, because they
were abstracted from existing school records and the smoking
information was not collected in a standardized manner. In a
Canadian retrospective study (1), a relative risk of 2.4 (p<0.001) was
found for stroke and smoking, but these results are also subject to
potential bias in the recording of the smoking history.

Hammond and Horn (15) studied the relationship between smok-
ing and disease among 187,783 white men, 50 to 69 years old,
followed from May 1952 through October 1955. Of the 11,870 deaths
during this period, 1,050 were from cerebral vascular lesions. A
statistically significant mortality ratio of 1.30 was found for smokers
and a dose-response relationship was apparent.

163
TABLE 2.—Mortality ratios for cerebrovascular disease
related to smoking, United States, 1969?

 

Mortality ratios (V=4,099), by age

 

 

Cigarettes/day 40-49 50-59 60-69 70-79
Males

Never smoked 1.00 1.00 1.00 1.00
1-9 2.79 1.95 1.30 0.95

10-19 1.14 148 1.44? 0.92

20-30 2.21 2.03 1.62 1.22

>40 1.64 2.40 1.72 0.68?

Females

Never smoked 1.00 1.00 1.00 1.00
1-9 1.50 1.26 1.26 0.83

10-19 2.60 2.70 2.15 0.573

20-30 2.90 2.67 1.83 1.28

>40 5.70? 3.52? _ -_

 

1 Population included 358,584 males and 445,875 females, 40-79 years of age at entry. Data collected from
questionnaire and 6-year followup of death certificate.

? Based on only five to nine deaths.

SOURCE: Hammond and Garfinkel (14).

In a large-scale prospective study of male British physicians, Doll
and Hill (8) found that the results differed somewhat between the
10th and 20th year of followup. A stroke mortality ratio of 1.2 was
found for smokers at the 10-year followup, with no dose-response
relationship evident. After 20 years of followup, a relative risk for
cerebral thrombosis of 1.52 was found for heavy smokers and a
strong dose-response relationship was apparent (9).

In an analysis of the 1,094 deaths that occurred among female
British physicians who had been followed for 22 years, Doll et al. (7)
found no effect of smoking on mortality from cerebral thrombosis;
however, there were only 68 such deaths.

The American Cancer Society studied prospectively more than a
million men and women enrolled in 1959, following them for 13
years. With 6 years of followup, mortality ratios for cerebral
vascular disease were found to be increased among male and female
smokers compared with nonsmokers, with the highest ratios evident
among the 40- to 49-year-olds (Table 2). The excess risk was not
present in either sex past age 70. There was no significant dose—
response relationship (13, 14).

A study of the differences in mortality ratios by the type of
cigarette smoked (29) and a later analysis of data from the American
Cancer Society study indicated lower mortality ratios from stroke
among males who smoked low tar and nicotine or filtered cigarettes
than among smokers of higher tar and nicotine cigarettes or of
“plain” cigarettes (6). No such differences were found among

164
females. A study conducted by the Tobacco Research Council in
England showed mortality ratios that were lower, but not signifi-
cantly so, among smokers of lower tar and nicotine cigarettes (6).

In 1965, Ostfeld began a prospective study among random samples
of the elderly in Cook County, Illinois, to determine variables
associated with stroke. They found that stroke-prone persons can be
identified even among the elderly. Stroke risk was higher among the
blacks and among persons with preexisting cardiovascular disease,
transient ischemic attacks (TIAs), diabetes mellitus, or hypertensive
cardiovascular disease. Cigarette smoking was, however, unrelated
to any class of stroke in the elderly, with or without preexisting
cardiovascular precursors (36).

Kimura (26) reviewed the results of six prospective studies of
cardiovascular disease in Japan and found a correlation of cigarette
smoking with myocardial infarction when accompanied by abnor-
malities in serum cholesterol and blood pressure; no relationship of
cigarette smoking to stroke was noted. Okada et al. (34) studied
stroke prospectively in Japanese men 40 years old or older residing
in two rural communities and found relative risks of intracerebral
hemorrhage and brain infarction among nonsmokers that were not
statistically significantly lower than those in smokers.

In an 8-year prospective study of a random sample of 35- to 59-
year-olds in two counties in eastern Finland, age, blood pressure,
diabetes mellitus, and previous stroke were found to be predictive of
stroke incidence in both men and women. Cigarette smoking and
serum triglyceride levels were found to be positively associated with
stroke among men, but not among the women (47). In an effort to
predict coronary heart disease and other mortality rates, Menotti et
al. (32) analyzed 14 CHD risk factors using a multiple logistic
function model. The study included 1,524 men between 40 and 59
from two rural areas in Italy who were measured for all 14 risk
factors upon entry. After 15 years, 37 men had had a stroke. Of the
14 risk factors considered, age and blood pressure were the only
factors found to be significantly associated with stroke risk, ranking
1 and 2, respectively. Smoking ranked third for predicting stroke,
but was not statistically significant.

In a retrospective study (16) of 126 stroke patients and 212
matched controls in Tilburg, Holland, a significantly increased risk
of stroke associated with cigarette smoking was not found. Hyperten-
sion was found to be related to stroke, and the risk was age
dependent, being strongest among the younger patients.

An investigation in Finland (70) of 128 men and 85 women under
50 years of age with ischemic stroke revealed 1.5 times as many
cigarette-smoking men and three times as many cigarette-smoking
women in the stroke group as in the Finnish population of the same
age. Hypertension, abnormal electrocardiographic findings, and oral

165
contraceptive use in women were also shown to increase risk. Ina
large prospective study (40) of women under 55 years of age in
California who were followed for 6.5 years, cigarette smoking
increased the risk of subarachnoid hemorrhage 5.7 times and use of
oral contraceptives increased it 6.5 times. The relative risk was 21.9
among women who both smoked and used the pill compared with
nonsmoking nonusers. In a case—control study (4) involving 12
university hospitals, 598 nonpregnant women with strokes between
age 15 and 44 were identified. Compared with controls, current use
of oral contraceptives was considerably higher in women with
thrombotic strokes (ninefold) and somewhat higher in women with
hemorrhagic strokes. It was also found that 74 percent were current
or past smokers. In an investigation of 75 hemiplegics aged 18 to 50
years, Steinmann (51) found that cardiac disease and hypertension
were the predominant risk factors. In men, but not in women, heavy
smoking was a risk factor.

Further confirming the general impression that cigarette smoking
is a stroke risk factor in young men are the results of three case—
control studies. Among 100 male stroke patients, aged 40 to 69, Koch
et al. (27) found a relative risk of 11.2 for smokers of more than 20
cigarettes a day. In a study (30) of 56 male and 34 female patients
under 66 years of age with cerebral hemorrhage or infarction,
significantly more stroke patients than their matched controls were
found to be smokers, and more smoked at least a pack of cigarettes a
day. Other factors predisposing to stroke in this study population
were high blood pressure, oral contraceptive use, and a family
history of stroke, plus cerebral neoplasm and thrombocytopenia. In
another study (52), among 39 male and 28 female ischemic stroke
patients, cigarette smoking was found significantly more frequently
among male cases than among matched controls. In the young
females, use of oral contraceptives was the predominant risk factor.

Haberman et al. (12) summarized mortality and incidence studies
dealing with smoking and stroke (Tables 3 and 4). They pointed out
that the relationship between smoking and cerebrovascular disease
is not a uniform finding of the epidemiologic studies of this disease
process. The authors cautioned that the studies are not strictly
comparable because of variations in methodologies, but they suggest-
ed that an association between smoking and stroke may exist but be
age dependent. An age dependency is suggested by the Framingham
and Paffenbarger studies.

Transient Ischemic Attacks

Some evidence connects cigarette smoking with transient ischemic

attacks (TIA). In a 6-year followup for TIA of 7,895 men aged 45 to 68
years in the Honolulu heart study (42), prior cigarette smoking was

166
TABLE 3.—Results of stroke incidence studies

 

Relationship between Approximate

 

Study Type ' Date Disease? stroke and smoking* relative risk
Hiroshima P 1958-64 cl None -
Washington P 1961-71 Stroke None 09

Cl None 0.8-1.1
Framingham P 1949-73 ABI Yes. Not sig 1.1-2.7 (males)
Manitoba R 1970-71 of Yes. Sig? 2.4
Rural Japan P 1964-70 Stroke Yes. Not sig 1.9-2.7
Harvard P 1916-66 Nonfatal CI Yes. Sig 16
Walnut Creek P 1969-76 SAH Yes. Sig 5.7
Queen Square R 1965-78 Aneurysm Yes. Sig? 3.8

 

1 P denotes prospective; R denotes retrospective.

* Cl: cerebral infarction; ABI: atherothrombotic brain infarction; SAH: subarachnoid hemorrhage.
*? denotes doubt about the study design.

SOURCE: Haberman et al. (12).

TABLE 4.—Results of stroke mortality studies

 

 

Relationship between Approximate

Name Type’ Date stroke and smoking mortality ratio
Longshoremen P 1951-69 None 11
Washington P,R 1962-71 None 0.9
Harvard P 1916-66 Yes 2.1
Dorn P 1954-62 Yes 13-19
British doctors

(10 year) P 1951-61 None 12
British doctors

(20 year) Pp? 1951-71 Yes 11-15
American Cancer

Society P 1959-65 Yes 1.3-2.8

 

 P denotes proapective; R denotes retrospective.
* Based on cerebral thrombosis only.
SOURCE: Haberman et al. (72).

associated with TIA, even in multivariate analysis taking other risks
into account. However, Ostfeld et al. (35) found conflicting results.

Subarachnoid Hemorrhage

A retrospective study (2) of patients with subarachnoid hemor-
rhage demonstrated an association with cigarette smoking. In this
study, smoking was estimated to increase the risk of a subarachnoid
hemorrhage almost fourfold in both sexes. In the Walnut Creek
contraceptive study this was confirmed, with a 5.7-fold increased risk
compared with nonsmokers (39). Also, in a 6.5-year followup of this
cohort of 16,759 white middle-class women aged 18 to 54, cigarette
smoking was associated with a fivefold to sevenfold relative risk of
subarachnoid hemorrhage and also with a 4.8-fold risk for other
strokes (40).

167
Smoking Cessation

Controlled clinical trial data measuring the effect of smoking
cessation on cerebrovascular disease are not available; observational
studies have been published. In the 16-year followup of 293,000
insured veterans (43), specific causes of death were studied in
relation to smoking status. Mortality ratios for ex-smokers were
found to be much lower than for current smokers. For stroke, the
mortality risk for the ex-smoker rapidly returned to the nonsmoker
rate after the cessation of smoking. Koch et al. (27) found an
increased risk of stroke in young patients that was not detectable in
ex-smokers after 1 year.

Oral Contraceptives

Oral contraceptives (OCs) have been widely used for more than 20
years, and many reports suggest that women who use them are at
increased risk of stroke (4, 5, 18, 44, 53, 54), Firm, undistorted
prospective data on the risk of cigarette smoking in women taking
OCs are sparse, owing to the generally low incidence of stroke in
women of childbearing age. Reliance is placed chiefly on retrospec-
tive data subject to unavoidable selective bias or on multicenter
prospective data based on small numbers of events. Such data as
exist strongly suggest a synergistic effect of smoking and oral
contraceptives that may be related to “hemorrhagic stroke” (42, 46),

In 1969, the Walnut Creek Contraceptive Drug Study began a long-
term study of the effects of OC use on the health of women aged 18 to
54 at study initiation. After 6.5 years of followup, Petitti and
Wingerd (39) analyzed the data from 15,260 women. The authors
found relative risks associated with OC use of 6.5 and 7.6 for
subarachnoid hemorrhage and thromboembolism, respectively. The
risk of subarachnoid hemorrhage for smokers was 5.7 times that for
nonsmokers; the relative risk of subarachnoid hemorrhage for
women who smoked and used oral contraceptives was 21.9. Among
the small number of ex-users, past use significantly increased the
risk of subarachnoid hemorrhage, but not of other vascular diseases
(39). In another study, cigarette smoking in itself was evidently not a
demonstrable risk factor for stroke among women, even at an early
age (42).

In a two-part review article, Stadel (48, 49) indicates that OC use
multiplies, rather than adds to, the risk of age and other factors in
the development of myocardial infarction (MI) and stroke. On the
basis of a total of only 31 cases reported in two studies and 134
reported in a third, Stadel (49) further indicates that current and
past use of OCs appears to increase the risk of subarachnoid
hemorrhage in women near age 35 or older (77). Stadel suggests that
the risk of cardiovascular disease among current users of oral

168
TABLE 5.—Annual death rate for oral contraceptive users
related to age, duration of use, and smoking

 

 

habits
User characteristic Annual death rate
Age group
15-34 years 1 per 20,000
35-44 years 1 per 3,000
45-49 years 1 per 700
Duration of use
< 5 years 1 per 8,000
> 5 years 1 per 2,000
Smoking habit
Nonsmoker 1 per 10,000
Smoker 1 per 3,000

 

SOURCE: McQueen (31), Royal College of General Practitioners (42).

contraceptives is related to the estrogen and progestogen content of
the pill.

A large prospective study in England (46,000 British women) found
that both the incidence and the mortality rates of a variety of
diseases, including cerebrovascular disease, were increased among
users of oral contraceptives versus nonusers (45). The number of
stroke deaths in the Royal College of General Practitioners (RCGP)
study was small; thus, risk estimates were subject to error. Women
over 35 and women who smoked and took oral contraceptives were
found to be at substantially higher risk than were nonsmokers and
nonusers of OCs.

Additional analysis of the RCGP study including followup through
1976 showed that current or previous users of oral contraceptives
had a standardized mortality rate for cerebrovascular disease 4.7
times that of controls. Increases in total death rates were found
among older women, women who had used the pill for 5 or more
years, and women who smoked cigarettes (44) (Table 5).

Results from a case-control study conducted by the Collaborative
Group for the Study of Stroke in Young Women (5) showed that
cigarette smoking and the use of oral contraceptives were indepen-
dent risk factors for subarachnoid hemorrhage; the relative risk was
2.6 for smokers and 4.1 for users of OCs. When a heavy smoker also
took oral contraceptives, the risk increased to 6.1 or 7.6, depending
upon the control group used for comparison. In an earlier report, the
same group (4) reported that risk of cerebral ischemia or thrombosis
was approximately nine times greater among women using oral
contraceptives than among nonusing controls. They also reported

169
However, former cigarette smokers appear to have a lower risk of
stroke than do continuing smokers.

The key to stroke prevention is early, vigorous, sustained control
of hypertension and the cardiac impairments that escalate the risk,
Cigarette smoking cessation may also play a role, particularly in
young male stroke candidates or in women using oral contraceptives.

atherosclerotic cardiovascular disease, including stroke.

Women cigarette smokers experience an increased risk for sub-
arachnoid hemorrhage; the use of both cigarettes and oral contracep-
tives appears to synergistically increase this risk.

170
Conclusions

1. Data from numerous prospective mortality studies have shown
an association between cigarette smoking and cerebrovascular
disease. This risk is most evident in the younger age groups, and
the effect diminishes with increasing age, with little or no effect
noted after age 65. No consistent dose-response effect has been
demonstrated.

2.Women cigarette smokers experience an increased risk for
subarachnoid hemorrhage. However, the use of both cigarettes
and oral contraceptives greatly increases the risk for subarach-
noid hemorrhage among women.

171
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