Changes in cardiac function of rats acutely exposed to nitrogen
dioxide were examined by electrocardiographic records. Bradycardia
and arrhythmias were observed following exposure to 20 ppm for 3
hours (76). These alterations were attributed to changes in parasym-
pathetic nervous activity following exposure. The levels used were
high relative to those obtained from unaged tobacco smoke. In
addition, it has been suggested that enzyme-inhibiting effects
associated with cigarette smoking are due to nicotine N-oxide and
nitrogen dioxide. Because thiols are readily oxidized to disulfides by
either nitric oxide or nitrogen dioxide, they are potent inhibitors of
thiol-dependent enzymes (116). In the presence of cigarette smoke,
scavenger cells such as macrophages may not be readily activated. In
the respiratory system, the major histological sites of damage by
nitrogen dioxide are the terminal and respiratory bronchioles and
the proximal portions of the alveolar ducts. N itrogen oxides are also
suspected of contributing to the development of pulmonary emphyse-
ma (43) and the acceleration of platelet aggregation (101).

Carbon Disulfide

Epidemiological studies have incriminated carbon disulfide (CS2)
as a factor for the increased risk of arteriosclerotic diseases in
workers in the viscose-rayon industry (39). The reported acute dose
levels of CS2 during workers’ exposure were 20 ppm and higher (39).
In cigarette mainstream smoke, carbon disulfide can amount to as
much as 4 pg per cigarette (72, 114). It appears that the sulfur-
containing amino acids and proteins and certain pesticides serve as
major precursors for CS2in tobacco smoke (16, 72).

Cadmium

The soil supplies tobacco with traces of cadmium (Cd), which are
selectively retained by the plant. Depending on the soil, the Cd in the
leaf can amount to a few parts per million (50). The mainstream
smoke of a blended U.S. cigarette may contain up to 0.2 pg Cd (97,
102). In the blood of cigarette smokers, Manthey et al. (99) found 2.47
+ 1.72 yg per liter; Cd levels in the blood of nonsmokers were only
0.43 + 0.22 ug per liter. Cd appears to accumulate in the kidney, and
has been found in higher concentrations in the kidneys of cigarette
smokers than of nonsmokers (118).

The potential consequences of increased lifetime exposure to low
levels of cadmium are not known. However, autopsy studies have
revealed increased cadmium levels in persons with emphysema and
hypertension (131). Cigarette smoke is known to contain traces of
cadmium (0.1 to 0.2 vg per cigarette) (97, 102). It is chiefly
accumulated in the liver and kidneys, and has been found in levels
about twice as high in the kidneys of hypertensive cigarette smokers
compared with nonsmokers in the normotensive range (113). It is

226
possible that an increased body burden of cadmium may be related
more directly to blood pressure (208), although animal studies have
implicated genetic differences in susceptibility to cadmium-induced
hypertension (709, 110). Furthermore, epidemiological studies may
be confounded by failure to separate cigarette smokers from drinkers —
of soft water in determining risk of elevated blood pressure from
cadmium intake (77).

Cadmium has also been implicated in accelerated atherogenesis
and altered lipoprotein patterns in White Carneau pigeons, a species
often used to investigate risk factors for arterial disease (119). The
results of these studies showed that the number and size of
atherosclerotic plaques were increased in pigeons given drinking
water containing cadmium or lead and that the lipoprotein profile
was altered in an independent fashion. The possible mode of action of
cadmium on atherogenesis is unknown, but endothelial damage is
suggested by the work of Rohrer and colleagues (121). In their
studies, pregnant rats received a single administration of cadmium
(0.5 to 2.0 mg/kg), and vacuoles were observed in the endothelial
cells of fetal brains. These vacuoles distorted the shape and
orientation of the endothelial cells in the caudate nucleus.

Data on the relation between cigarette smoking and cadmium
' intake remain inconclusive. Drinking water and genetic factors may
overwhelm the effects of cadmium as a cigarette smoke constituent
on cardiovascular disease, and more work in this area is necessary
before a cause and effect assignment can be made.

Zinc

The average zinc (Zn) content in commercial cigarettes varies
between 50 and 80 ppm (140) and in the mainstream smoke of U.S.
cigarettes between 0.05 and 0.4 pg (102). So far, Zn has been
determined only in the urine of cigarette smokers, where it occurs in
significantly higher concentration than it does in the urine of
nonsmokers (46). Zinc is a metal component of many important
enzyme systems; its availability controls the rate of synthesis of
nucleic acids and protein (98). In fact, zinc deficiency has been
associated with poor growth (30), and depressed plasma zinc levels
have been used as indicators of myocardial infarction (94. In
general, low zinc levels have been found to be associated with

depressed health status, and supplemental zinc has not been
correlated with increased risk of disease development.

Tar

The total particulate matter (TPM) of a cigarette, often referred to
as tar, is defined as that portion of the smoke that is retained by a
glass fiber filter. This definition is widely accepted and can be
regarded as a quantitative approach, since the Cambridge glass fiber

227
filter retains 99.9 percent of particles of the mainstream smoke that
have diameters of >0.2 » (154). Different methods of smoking
cigarettes and of determining tar in the smoke have been applied
throughout the world; this needs to be considered when comparing
data on cigarette smoke yields in various countries (28).

According to the U.S. Federal Trade Commission report of March
1983, the tar yields of commercial U.S. cigarettes vary from <0.5 to
30 mg (146). All cigarettes with >20 mg tar yield are nonfilter
cigarettes, and practically all cigarettes with tar yields <12 mg are
cigarettes with perforated filter tips (146). As discussed before, it has
to be realized that the standard machine smoking method developed
for a comparison of the smoke yields of commercial cigarettes does
not reflect the average smoking habits of cigarette smokers, especial-
ly of those who smoke low-nicotine cigarettes (64, 65, 89, 127). A
person’s smoking habit is largely dependent on the smoker’s need for
nicotine. Consumers of low-nicotine cigarettes take larger puff
volumes and inhale more frequently than do the smokers of
cigarettes with high nicotine yields (>1.0 mg cigarettes) (64). At
present, the most reliable assay for determining the uptake of
particulate matter by an individual smoker is seen in the analysis of
nicotine and cotinine in his or her serum (58).

In theory, reduction of the toxic components in cigarette smoke
should reduce the risk for neoplasms and cardiovascular diseases.
Therefore, the introduction of filter cigarettes, which should pre-
clude the inhalation of some of the tobacco tar constituents, would be
expected to reduce the incidence of respiratory and cardiovascular
dysfunctions. End point analysis of the long-term followup of the
Framingham cohort made it possible to test the hypothesis that
those who smoke filter cigarettes would be less likely to manifest
clinical symptoms of cardivascular disease than would those who
smoke nonfilter cigarettes. Despite what seemed a more favorable
smoking history, the filter cigarette smokers did not have lower
incidence rates of cardiovascular diseases than the nonfilter smok-
ers. This finding was unchanged after multivariate logistic regres-
sion analysis to adjust for age, systolic blood pressure, and serum
cholesterol (32). The relationship of this seemingly negative finding
to the tar component of tobacco smoke must remain imprecise
because other smoke constituents covary with the tar fraction.

Respiratory complications and immune hypersensitivity have
been correlated with intake of particulate phase components of
tobacco smoke. Cigarette smokers exhibit greatly increased risks for
pulmonary diseases, including emphysema and chronic obstructive
lung disease (144). Such diseases can also place increased stress on
the cardiovascular system. Cigarette smokers demonstrate more
frequent macroscopic and microscopic lung abnormalities than do

228
nonsmokers, with a dose-response relationship being apparent in
regard to these changes and the self-reported intensity of smoking.

Research Needs and Priorities

The evidence linking cigarette smoking to cardiovascular diseases
is strong. Understanding of the mechanisms whereby cigarette
smoking initiates or accelerates disease processes remains imprecise
because a variety of smoke constituents exert multiple effects upon
body systems.

Epidemiologic studies have correlated increases in atherosclerotic
CVD death rates with increased use of cigarettes and also have
shown that those persons who stop smoking do in fact exhibit lower
death rates than those who continue to smoke. Despite the demon-
strated association of smoking with enhanced atherogenesis, risk of
coronary death in persons who stop smoking appears to revert to
lower levels in a relatively short period following cessation. It is
quite likely that the precipitating events leading to thrombus
formation and occlusion are decreased, although fibrous plaques will
not regress so rapidly (82).

Methods for cessation of cigarette smoking, especially among high
risk populations, must be a priority in the research endeavor to
reduce cardiovascular disease morbidity and mortality. Although
termination of the habit is the ideal goal, it must be recognized that
this is a difficult task for a number of smokers.

Reduction of the harmful components delivered to the smoker has
been another priority objective, aimed at those smokers who will not
give up the habit. This task has resulted in the introduction of a
variety of low- and ultra-low-yield cigarettes. Whether risks for
cardiovascular diseases are truly reduced when these products are
used remains to be demonstrated. Several recent studies have shown
that smokers alter their smoking behavior when they switch to low-
yield cigarettes and can receive increased smoke constituents as they
attempt to satisfy a nicotine demand (64, 65). This compensatory
behavior may lead to accelerated atherogenesis through increased
uptake of smoke constituents such as carbon monoxide, hydrogen
cyanide, and nitrous oxides. Recently it was reported that the risk of
a nonfatal first myocardial infarction in young men was not related
to the nicotine or carbon monoxide levels of the cigarette. This could
be due to compensatory behavior (83).

‘One should not ignore the proportion of the population that
continues to smoke, nor should one accept unchallenged the concept
of a “safe” cigarette. The main objective is to reduce the harmful
constituents present in tobacco smoke. It is probable that promotion
of ultra-low-yield products will not suffice, since compensatory

229
mechanisms may be triggered by sensory needs for taste as well as
for nicotine.

A cigarette considered less harmful for cancer etiology might not
reduce the risk for coronary disease. It appears to be a formidable
task to develop a product that satisfies the smoker and does not
increase disease risk through exposure to carbon monoxide, hydro-
gen cyanide, nitrous oxide, or still unknown agents.

Of the major cardiovascular risk factors, cigarette smoking is a
powerful, prevalent, and potentially correctable contributor that
deserves the highest priority among preventive measures to control
cardiovascular disease (82).

Conclusions

1. Over 4,000 different compounds have been identified in tobacco
smoke.

2. Nicotine exerts an effect on ganglionic cells, producing transient
excitation. The pharmacological effects are small, but are
reinforced several times daily in habitual smokers. The exact
mechanisms whereby nicotine might influence cardiovascular
events are unknown, but a lowering of the ventricular fibrilla-
tion threshold is dose related to nicotine levels.

3. Carbon monoxide may act to precipitate cardiac symptomatolo-
gy or ischemic episodes in individuals already compromised by
coronary disease. In addition, carbon monoxide binds to hemo-
proteins, potentially inhibiting their functions.

4. Several studies have shown that smokers may alter their
smoking behavior when they switch to low-yield cigarettes. This
compensatory behavior may lead to the increased uptake of gas
phase constituents including carbon monoxide, hydrogen cya-
nide, and nitrous oxides.

5. It is unlikely that a “safe cigarette” can be developed that will
reduce cardiovascular risk.

230
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SECTION 7. CHANGES IN
CIGARETTE SMOKING
BEHAVIOR IN
CLINICAL AND
COMMUNITY TRIALS

241
Introduction

This section examines the changes in cigarette smoking behavior
resulting from intervention strategies. The next section presents
detailed data on CHD outcome resulting from these trials compared
with those prospective epidemiologic studies for which cessation
outcome information is available.

Large-scale primary preventive trials have used both single and
multifactorial intervention in high risk populations in an attempt to
test the effect of the modification of major risk factors, either alone
or in combination, on coronary heart disease (CHD) or respiratory
disease. Several of these trials have been developed and implement-
ed since the early 1970s, and provide a valuable opportunity for
assessing the efficacy and outcomes of smoking intervention tech-
niques in particular high risk populations and the impact of smoking
behavior change on disease. The objective of this section is to present
and critically appraise the smoking intervention programs and the
smoking cessation outcomes in the large-scale controlled preventive
trials.

At present there are two types of preventive trials in cardiovascu-
lar or respiratory disease that either have been completed or are
currently in progress. One type includes clinical investigations in
which individuals are randomized either to an intervention group
for a risk factor reduction program or to their usual source of
medical care. These randomized trials are either single factor trials
that intervene on one variable such as cigarette smoking, as in the
London Civil Servants smoking trial (55, 60, 61), or multifactorial
trials that generally attempt to change the alterable risk factors of
cigarette smoking, hypercholesterolemia, and hypertension, or some
combination of these risk factors. In this group are the Géteborg
(Sweden) trial (78, 79, 80), the Oslo (Norway) study (26, 17), and the
Multiple Risk Factor Intervention Trial (MRFIT) (79, 43).

The randomization of entire populations to an intervention or a no-
intervention group comprises the second type of trial. In this group
of community investigations are trials based on random allocation of
factories to intervention or regular care, as in the WHO study (62),
which involves four centers—London, Brussels/Ghent, Rome, and
Warsaw—using a common protocol, and trials in which entire
geographic areas are randomized, as in the North Karelia project
(52, 53, 54, 63, 64, 65). Although the Stanford study has been
described by its investigators as a community-based investigation
(13, 14, 36, 41), it did not involve random allocation of communities
and thus does not belong in this group as defined here. Although the
Stanford group studied three different communities, individuals
within one community were randomized to intensive or to communi-
ty intervention only. Therefore, for the purposes of this review, the

243
Stanford study will be included with the first group of trials,
although it somewhat overlaps both groups.

Smoking intervention methods and smoking behavior change
outcomes for each of these trials will be presented and critically
evaluated. These prospective studies use experimental design meth-
odology that maximizes comparability of treated and untreated
groups by maintaining a high degree of quality control on all aspects
of randomization, data collection, and evaluation; by utilizing
unbiased statistical treatment of the data; and by detailing a priori
specification of the intervention (38).

A major problem in assessing outcomes of smoking intervention
studies has been research that has often been poor in methodology,
quality control, and design. Although preventive trials have general-
ly conformed to the desired methodology as noted above, they too, as
with other smoking intervention studies, have been deficient in some
of the methods used or in the reporting of the data. The deficiencies
of smoking intervention studies have been well reviewed in past
investigations (5, 34, 45, 67) and will be only briefly summarized here
to provide a basis on which to critically review the research and
smoking intervention designs in preventive trials.

Problems in Smoking Intervention Studies
Lack of Objective Data to Verify Self-Reported Outcomes

A major deficiency in smoking cessation evaluation research has
been the use of self-reported smoking data that have not been
validated with objective measures. These data depend on the
subjects’ honest and accurate reporting and often lead to an
overestimation of success, especially among participants who feel the
pressure to stop smoking, as in an intervention program. Neaton et
al. (46) found that when the reported quit-rate of the intervention
group in MRFIT was adjusted using serum thiocyanate (SCN) levels,
the overreporting ranged from 5 to 9 percent, while a much smaller
overreporting rate was found in the usual care group not treated in
the program. The demand characteristics of the intervention pro-
gram may prompt some individuals to falsely comply with the
expectations of the interventionist (2).

One approach to validation of self-reported data involves the use of
serum thiocyanate (SCN) determinations as objective measures of
smoking status, with a critical cutoff point used to differentiate
smokers from nonsmokers (3). SCN is the metabolite of hydrogen
cyanide, a pyrrolic product in tobacco smoke. In addition to cigarette
smoking, SCN may be elevated by the use of pipes, cigars, or
cigarillos. However, the interpretation of SCN concentration is
potentially confounded by at least two factors. Certain foods,
particularly those of the Brassica genus (cabbage, cauliflower, kale,

244
kohlrabi, broccoli, brussels sprouts, turnips, and rutabagas), as well
as fruit pits and almonds, may elevate levels. Also, diuretics tend to
raise SCN levels by an average of 8 pmol/liter (51). With such
limitations in mind, the biologic half-life of SCN, approximately 14
days (51), still makes it a measure well suited for corroboration of
self-reports. Determinations of SCN in saliva and urine have also
been used and are more adaptable to some settings (11, 42).
Measurement of carbon monoxide (CO) concentrations in serum or
expired air also can be used as a validation tool (29, 57, 76). The
major drawback of this measure is CO’s short half-life of several
hours (56, 72); it may also be affected by various environmental
factors (72, 77).

The most specific objective indicator of tobacco use is nicotine
itself or its major metabolite cotinine, both of which can be measured
in blood, saliva, or urine (22, 31). The extremely short half-life of
nicotine, on the order of 30 minutes, makes it unsuitable for
verification of cessation or for quantifying estimates of tobacco
intake, but the 20- to 30-hour half-life of cotinine is much more
useful for these purposes (4, 82). Unfortunately, cotinine analyses
are rarely used in clinical trials because of the expense and the
relative unavailability of the complex analytic technique compared
with SCN determination.

Lack of Comparison Groups

Only recently have clinical assessments of smoking in intervention
programs been more consistent in their use of an experimental
design that includes random allocation to the experimental smoking
cessation condition or to an appropriate comparison group. Investi-
gators using a minimal treatment or attention-placebo comparison
group have demonstrated that these groups produce smoking
cessation results beyond those that no intervention would be
expected to produce (28, 32, 37). These outcomes have been partially
accounted for by certain “nonspecific factors” common to all
treatment settings and cannot be attributed to a specific interven-
tion technique. These nonspecific factors include the use of self-
monitoring, a structured program that promotes the expectation of
success, and a therapist’s attention (J, 5, 40). Determination of the
effect of a proposed treatment on outcome results is not possible
without rigorous designs that include appropriate experimental
controls, preferably a minimal-treatment control group (37).

Classification Differences

Smoking control studies use variable criteria for grouping individ-
uals; this makes it difficult to compare outcomes. For example,
Straits’ (73) successes achieved at least an 85 percent reduction in
smoking, whereas Keutzer’s (25) successes achieved at least a 50

245
percent reduction. Kanzler et al.’s (23) “continuing successes” (3 1/2
to 4 years after treatment) were subjects who had not recidivated at
any time for “longer than a week,” while Ockene et al.’s (50)
“continuing successes” were at zero cigarettes for at least 2 years,
and self-reports were validated with SCN measurements.

Similarly, in some studies a smoker is someone who smokes pipes,
cigars, or cigarettes (e.g., Oslo study), while in other studies a subject
is classified as a smoker on the basis of whether or not he or she
smokes cigarettes only (e.g., MRFIT). Because of the lack of
consistency in groups compared and criteria used, outcomes of
studies are difficult to evaluate, and cross-validation can provide

onflicting outcomes. In order to avoid these problems, standard
classification categories have been suggested (69).

Followup Differences and Deficiencies

Experimental studies of smoking have used different followup
points to assess outcomes and to determine predictor variables.
These followup points have included immediately post-treatment
(25), 2 weeks’ post-treatment (2), 3-month followup (22), 6-month
followup (6), 1-year followup (70), and 3- to 4-year followup (23, 30,
50). In most studies, cessation rates at followup points refer to
“nonsmoking prevalence” at that point in time, rather than to
continued abstinence from immediately post-treatment onward.
Such studies give no indication of the dynamics of cessation and
relapse that determine the nonsmoking prevalence rate, nor do they
indicate what is happening long term with a cohort of smokers.
Ockene et al. (48, 49), in their analyses of the smoking data from the
Multiple Risk Factor Intervention Trial (MRFIT), demonstrate the
importance of following cohorts of smokers from baseline to followup
points in addition to determining cessation rates at a single point in
time. Careful definition of cessation rates should be given in all
research reports so that the reader can distinguish whether a given
rate refers to a single probe measure or to a quit status of some
known duration. Shipley et al. (71) have discussed this problem in
depth and offered potential standards for reporting in the smoking
cessation literature.

Because of the high recidivism rate in the first year of abstinence
(20), the comparison of a study that measures cessation at immediate
post-treatment to one that assesses cessation at 1-year post-treat-
ment will demonstrate very different outcomes. As explained above,
the smoker reporting cessation at immediate post-treatment could
become either a continuing success or a recidivist at l-year post-
treatment. In effect, comparing stoppers at different points is similar
to comparing different groups (47). The smoker’s continuing suscepti-
bility to relapse, even after being cigarette free for more than 2
years, needs to be reflected in smoking research and intervention by

246
the inclusion of followup and maintenance programs beyond the
usual 6 to 12 months (49).

Most studies also fail to note whether a followup point (e.g., 1 year)
indicates a period of time since the entire study began or since the
smoker entered the program. If it indicates the former, it is possible
that there is a different length of followup for participants in the
same study, depending on when they entered the program. Outcomes
for these participants should not be compared unless appropriate
analytic techniques such as life tables (7) or person-years (7) are used
to adjust for the differing lengths of followup.

Methods of Data Reporting

The continuing susceptibility of the smoker to relapse, as well as
the fact that it is long-term rather than short-term cessation that has
an impact on disease outcomes (48, 49), needs to be reflected in the
way data are reported in smoking cessation research, although this
rarely occurs. Cross-sectional cessation data are generally measured
and reported giving little indication of the dynamics of cessation and
relapse that determine the cessation rate at any one point in time
(49). Thus, a cessation rate of 30 percent at 2-year followup does not
mean that 30 percent of the smokers in a study remained cigarette
free for 2 years. Perhaps only 10 percent were nonsmokers for the
entire 2-year period. Studies of smokers quitting both with and
without formalized aid show that people often pass through several
cycles of cessation and relapse before permanent cessation is
achieved (70, 56). Analysis of data from cohorts of baseline smokers
followed longitudinally provides a more complete understanding of
smoking behavior change and “true” long-term cessation. It also
provides relevant data for evaluating the effect of cessation on
disease outcome. Cohort analyses are missing in all but a very few
studies.

The primary evaluation of treatment results should be based on
abstinence data for several reasons, as summarized by Pechacek (75),
including the following: abstinence is the primary goal of most
smokers enrolled in programs; smoking behavior change followup
data have indicated that most smokers who reduce their smoking
without totally stopping return to baseline smoking levels; a
clinically insignificant proportion of smokers at followup can be
abstinent and yet analyses of rate data can show statistically
significant treatment effects; and reports of abstinence rather than
reduction are less susceptible to exaggeration and the demands of
the program placed on the smoker. In spite of the importance of
cessation data and of true long-term data, these are often missing in
outcome reports.

247
The Use of Various Methods for the Determination of
Treatment Outcomes

Methods for determining treatment outcomes include telephone
calls (23), in-person interviews (19, 70), and mailed questionnaires
(12). The variability of the groups of smokers reached by these
different methods and their effects changes the criterion groups and
can be responsible for an extraneous source of variance leading to
distortion of the comparisons. Those subjects who respond immedi-
ately to smoking behavior assessment or followup are more often ex-
smokers, but those reached only after repeated tries are often smokers
(68). Therefore, the success and failure groups in a study in which
there is a high followup response (19, 47, 70) may be quite different
from these same groups in a study with a followup response of less
than 50 percent (23). It would be valuable to pursue a random sample
of nonresponders in order to be able to study and compare
responders with nonresponders in terms of generalizability of
outcomes.

Lack of Information and Precautions Needed to
Adequately Interpret Outcomes

A smoking cessation program or trial cannot be adequately
evaluated or interpreted without sufficient information about the
methods used in the design and implementation of the study, the
data included for determination of outcomes, and the methods used
for the analysis of the outcomes (9). DerSimonian et al. (9) surveyed
67 clinical trials reported in 4 well-respected medical journals, and
found that only 56 percent were clearly reported with respect to 11
important variables. The 11 variables were selected with regard to
their importance in determining the confidence that a reader could
place in the author’s conclusions, their ability to be discerned by the
scientifically literate general medical reader, and their applicability
across a variety of medical specialties.

A related point specifically aimed at the clinical trials reviewed in
this section is the need to specify all treatments other than smoking
cessation (e.g., modification of other risk factors) that participants
received. What precautions should be taken comparing smoking
cessation results from a trial modifying only smoking behavior to a
trial simultaneously modifying several risk factors? Specific as well
as nonspecific treatment differences are probably operative on
outcomes.

In summary, a critical evaluation of any smoking intervention
program needs to consider the deficiencies inherent in the study and
data analysis design as well as the deficiencies manifested in the
study report by the lack of adequate information. Precautions
regarding comparison with other studies and generalizations should
also be considered. In the following section, the eight major large-

248
scale preventive trials implemented since 1970 that include a
smoking intervention component and have reported smoking cessa-
tion outcomes will be reviewed. (Three-year followup data are
available for most of the trials; therefore, whenever possible these
data will be presented in addition to whatever other data are
available and relevant for comparisons.)

Individual Allocation Trials
Single Factor Controlled Clinical Trials
The London Civil Servants Smoking Trial

The participants in the London Civil Servants smoking trial were
drawn from the 16,016 men, aged 40 to 59, who had undergone a
cardiorespiratory screening examination in the Whitehall study of
London Civil Servants carried out between 1968 and 1970 (55, 60, 61).
The results of the screening were used to select smokers for the trial
who had the highest risk of CHD or chronic bronchitis or both, based
on a risk score calculated from the multivariate combination of risk
factors (60, 61). Men were excluded if they had heart disease, severe
hypertension (DBP>115 mm Hg), diabetes mellitus, or major
concomitant disease; were taking psychotropic drugs; or had a
history of previous inpatient psychiatric treatment. The selected
men were randomly allocated to an intervention group (IG) or to a
“normal care” (NC) group. The results were first sent to the
participants’ general practitioners, who had the opportunity to
withdraw their patients from the study. Random allocation resulted
in an intervention group of 714 men and a control group of 731 men
(Table 1). The two groups were well balanced on all characteristics
measured, with a mean age of approximately 53 years and a mean
number of cigarettes smoked of 19 in the two comparison groups.

The smokers randomized to the intervention group were sent a
letter inviting them to come and discuss “one or two points
personally with a physician” (58). This session took about 15
minutes, and the smokers were advised of the health gains of
cessation rather than the dangers of continuation and then asked to
decide if they wanted further help and support (58, 59, 60). Booklets
prepared for the study were handed out at this visit. Most men
indicated that they would like help and were seen on an average of
three more visits in the first 10 weeks, and then at 6 months, with
each visit taking about 15 minutes. The only other health advice
given was on calorie restriction for those who gained weight. Close
contact was maintained over several months, and help was available
for those smokers who continued to need it. A special substudy was
implemented in which a group of intervention participants were
randomly allocated either to the usual procedure of further contact

249
Ose

TABLE 1.—Population, randomization,

trials

and baseline smoking data for five major controlled clinical

 

Clinical trial
(duration)

Population

Randomization methods/
study groups

Baseline age and
smoking data

 

 

London Civil Servants 1,445 healthy males Randomized to smoking X age = 53
Smoking Trial intervention or normal care X cigs = 19
(60, 61) Aged 40-59
(10 years) High risk for CHD and/or Intervention (IG) = 714 males
chronic bronchitis based on Normal care (NC) = 714 males
risk score
Goteborg (Sweden) 30,000 males Randomized to intervention X age = 51
Study for smoking, hypertension, X cigs = ?
(78, 79, 80) Aged 47-54 hypercholesterolemia, and
(4 years) Living in Géteborg low physical activity; or to 65% of 7,455 screened
(Screening 1970-1974) control group in IG were smokers
(Reexamination:
1974-1977) Intervention group (IG) = 10,000 males 16% of IG smoked

Two control groups (CG) = 20,000 males

215 cigs/day

 

Oslo (Norway) Study
(16, 17, 18)
(5 years)

1,232 healthy normotensive
males

Aged 40-59

Upper quartile CHD risk
based on risk score

Randomized to intervention
for smoking and cholesterol,
or to control group

Intervention group (I) = 604 males

Control group (C) = 628 males

X age = 45
X cigs (I) = 125
X cigs (C) = 13.0

80% were smokers