(Circulation. 1998;97:1871-1873.)
© 1998 American Heart Association, Inc.
Passive Smoking and Coronary Heart Disease
Dr Gio Batta Gori
The Health Policy Center,
Bethesda, Md
To the Editor:
In the past, Kawachi et al have been deservedly cautious in
interpreting their surveys of the Nurses Health Study cohort, but they
seem to have thrown caution to the wind in their article, "A
prospective study of passive smoking and coronary heart
disease" (Circulation. 1997;95:2374-2379), as reflected by
explosive reports in the news.
In earlier reports by the authors, lack of statistical significance
usually prevented conclusions of causality, coupled with a keen concern
about confounding and bias. Indeed, this article criticizes other
studies that have not adjusted "for the full range of
potential confounding factors," while the authors claim to
have adjusted "for a broad range of
cardiovascular risk factors"-adjustments that have
markedly reduced all crude risks, making most of them not statistically
significant. It is not clear, however, what further reductions would
have been achieved if the study had also adjusted for other confounders
previously identified by the same authors in the same cohort and for
which directly applicable data must have been at hand-notably the
considerable influence of shift work,1 weight
change,2 trans-fatty acid
intake,3 and height.4
Possibly, such adjustments might have been inconsequential, but the
report is silent.
Although the study is said to represent the prospective
experience of >32 000 nurses, a scant 152 cases make it comparable to
a modest case-control study subject to the uncertainties of a remote
one-time determination of exposure, of misclassification, and of
clinical verification of markers-inter alia-as the report
acknowledges. The authors mention the negative reports from the
American Cancer Society and National Mortality Followback Survey
databases5 6 7 but resist warning that a
nonsignificant risk from their frail database is inconsistent
with the no-risk reports from those very much larger databases.
The authors are justifiably troubled in endorsing passive smoking risks
substantially greater than the CHD risk attributed to active smoking by
the Surgeon General.8 In attempting to circumvent
the problem, however, they appear to have produced a larger one by
arguing that the CHD risk of active smoking is understated because
smokers are usually compared with nonsmoking control subjects, many of
whom are exposed to passive smoking CHD risk. Yet, smokers are also
exposed to passive smoking risk at doses and durations far exceeding
nonsmoker exposures, which would call for a drastic reduction of the
apparent risk attributable to active smoking, assuming the argument and
the high passive smoking risks claimed in this report were true.
The article laments the absence of a positive gradient in relation to
exposure duration and adduces uncertainties of recall as a reason, but
it should be said that the absence of a gradient could very much be
real. Also, the authors insist in relating risks to "women," and
although it may be true that all nurses of this cohort are women, not
all women are nurses. The authors themselves have documented in almost
100 articles that the women of the Nurses Health Study are quite
exceptional and hardly representative of the US female
population.
Speculation, of course, is essential and cognoscenti may see through
the lines, but feeding such problematic messages to the
unwary media challenges responsibility, especially if messages are
endorsed by presumed luminaries. Of course, I may be blinded as an
occasional consultant to the tobacco industry-still, if there
are no answers to the points just raised, perhaps the authors or the
Circulation editors might consider releasing appropriate
cautionary messages to correct what may have become quite unwarranted
public perceptions.
References
1.
Kawachi I, et al. Circulation.. 1995;92:3178–3182.[Abstract/Free Full Text]
2.
Willett WC, et al. JAMA.. 1995;273:461–465.[Abstract/Free Full Text]
3.
Willett WC, et al. Lancet.. 1993;341:581–585.[Medline]
[Order article via Infotrieve]
4.
Rich-Edwards JW, et al. Am J Epidemiol.. 1995;142:909–917.[Abstract/Free Full Text]
5.
Layard MW. Regul Toxicol Pharmacol.. 1995;21:180–183.[Medline]
[Order article via Infotrieve]
6.
LeVois ME, Layard MW. Regul Toxicol Pharmacol.. 1995;21:184–191.[Medline]
[Order article via Infotrieve]
7.
Steenland K, et al. Circulation.. 1996;94:622–628.[Abstract/Free Full Text]
8.
The Health Consequences of Smoking.
Cardiovascular Diseases: A Report of the Surgeon
General. Rockville, Md: US Public Health Service, Department of Health
and Human Services; 1983.
Response
Ichiro Kawachi, MD, PhD
Harvard School of Public Health,
Boston, Mass
Dr Adlkofer suggests that selection bias could have accounted
for our finding of an association between passive smoking and CHD. This
possibility is based on two assumptions: that passive smokers were less
likely to visit their doctors and receive a diagnosis of CHD, and that
excluding women with a history of CHD at the beginning of each
follow-up period led to a higher prevalence of undiagnosed CHD cases in
the group of passive smokers. We believe that both assumptions are
untenable. The Nurses' Health Study participants are all registered
nurses and have excellent access to health care. For instance, in 1992
when we asked about the participants' screening behaviors, only 2.4%
of the cohort had not had their blood pressure checked during the last
2 years. Moreover, there were no important differences in screening
behavior according to passive smoking status. Dr
Adlkopfer suggested that selection bias was introduced by our exclusion
of women with a history of CHD at the beginning of each follow-up
period. As we mentioned in our article (p 2375),1
we did this to avoid potential misclassification caused by women who
alter their exposure to passive smoking after developing a major
illness and to assess newly incident disease in a population at risk.
By using this methodology, 20 medically confirmed cases of CHD were
excluded during the 10-year follow-up period. When we repeated the
analysis including these 20 cases, the
multivariate adjusted relative risk of total CHD among
regular passive smokers compared with women not exposed was 1.73 (95%
confidence interval [CI], 1.06 to 2.84) compared with the estimate of
1.91 (95% CI, 1.11 to 3.28) published in our
article.1
Both Dr Adlkopfer and Dr Coggins question the plausibility of the
magnitude of the relative risks we obtained by comparing them with
smaller relative risk estimates obtained from other studies of active
smoking-for example, the American Cancer Society (CPS II) Study, which
reported a relative risk of 1.8 for CHD in female smokers. On this
issue, Drs Adlkopfer and Coggins were selective in their choice of
cited studies; we are aware of just as many cohort studies (eg, the
Swedish cohort study by Cederlof et al,2 the
Rancho Bernardo Study,3 the Finnmark
Study,4 and our own Nurses' Health
Study5 ) that found relative risks of CHD of
between 2.6 and 3.6 in female current smokers.
Dr Coggins simply reiterates the limitation that we already
acknowledged in our article, that measurement of passive smoking was by
self-report and at baseline only. Yet, as we discussed in our
article1 as well as
elsewhere,6 any resulting random
misclassification of exposure could only change the relative risk
estimates in the direction of the null. If misclassification were
nonrandom, the "nonexposed" group in our study is more likely to
have included passive smokers than vice versa, because people
consistently underestimate their exposure to secondhand
smoke.6 Furthermore, workplace restrictions on
smoking became more common during the study period, so that the
"exposed" group in our study probably became progressively mixed
with women who were no longer exposed. Both types of misclassification
push the relative risk estimates in the direction of the null.
Although Dr Coggins questions our use of questionnaire assessment of
ETS exposure, he himself places much weight on the study by
Layard,7 which also used questionnaires completed
by surrogate respondents. We did not cite Layard's pooled estimate of
relative risks across just three studies because a more thorough
meta-analysis incorporating data from 12 studies has been
published,8 which suggests a statistically
significant increase in risk of CHD with passive smoking.
Dr Brennan suggests that studying the risks of passive smoking is
analogous to making mountains out of molehills. We were unable to
follow the logic of his calculations; however, we would point out that
according to credible estimates,9 some 35 000 to
40 000 deaths from coronary disease each year may be
attributable to passive smoking.
Dr Gori speculates about how our relative risk estimates might have
been influenced by adjusting for other risk factors such as height and
shift work. As we stated in our article,1 we
adjusted for a very broad range of factors that we determined a
priori to be potential confounders. The reason for not adding shift
work to our models was that this exposure was not assessed until the
1988 questionnaire,10 whereas passive smoking was
ascertained in 1982. We nonetheless repeated our analysis from
1988 through 1992, including shift work as a covariate. On the basis of
73 cases of total CHD, the multivariate adjusted
relative risk among women regularly exposed to passive smoking compared
with those never exposed was 2.12 (95% CI, 0.92 to 4.89). This point
estimate is quite similar to the relative risk of 1.91 reported in the
full study; the width of the 95% CIs reflects the halving of cases
caused by shorter follow-up duration. Lacking a sound rationale as to
why other variables such as height might act as important
confounders in the relation between passive smoking and
coronary disease, we believed that it would be pointless to
keep adding more variables to our models.
We were puzzled by why Dr Gori refers to the American Cancer Society
CPS-II Study11 as a "negative report."
Although two consultants funded by Philip Morris published an
analysis of the CPS-II study reporting no association between
passive smoking and CHD risk,12 this report was
superseded by a more thorough analysis carried out by the
American Cancer Society investigators, which did report a positive
association.11
Finally, Dr Gori states that we "have documented in almost 100
reports that women of the Nurses' Health Study are quite exceptional
and hardly representative of the US female
population." Although this population was selected for study because
their training and motivation would provide superior data quality,
there is no reason to believe that biological relations based on our
findings are not relevant to women in general.
References
1.
Kawachi I, Colditz GA, Speizer FE, Manson JE, Stampfer
MJ, Willett WC, Hennekens CH. A prospective study of passive smoking
and coronary heart disease. Circulation. 1997;95:2374–2379.[Abstract/Free Full Text]
2.
Cederlof R, Friberg L, Hrubec Z, Lorich U. The
Relationship of Smoking and Some Social Covariables to Mortality
and Cancer Morbidity: A 10-Year Follow-up in a Probability Sample of 55
000 Swedish Subjects Age 18 to 69. Stockholm, Sweden:
Karolinska Institute, Department of Environmental Hygiene;
1975.
3.
Barrett-Connor E, Khaw KT, Wingard DL. A ten-year prospective
study of coronary heart disease mortality among Rancho Bernardo
women. In: Eaker ED, Packard B, Wenger NK, Clarkson TB, Tyroler HA,
eds. Coronary Heart Disease in Women. Bethesda, Md:
National Heart, Lung, and Blood Institute, National Institutes of
Health; 1987.
4.
Njolstad I, Arnesen E, Lund-Larsen PG. Smoking, serum lipids,
blood pressure, and sex differences in myocardial infarction: a 12-year
follow-up of the Finnmark Study. Circulation. 1996;93:450–456.[Abstract/Free Full Text]
5.
Kawachi I, Colditz GA, Stampfer MJ, Willett WC, Manson JE,
Rosner B, Speizer FE, Hennekens CH. Smoking cessation and time course
of decreased risks of coronary heart disease in middle-aged
women. Arch Intern Med. 1994;154:169–175.[Abstract/Free Full Text]
6.
Kawachi I, Colditz GA. Confounding, measurement error, and
publication bias in studies of passive smoking. Am J
Epidemiol. 1996;144:909–915.[Free Full Text]
7.
Layard MW. Ischemic heart disease and spousal smoking
in the National Mortality Followback Survey. Regul Toxicol
Pharmacol. 1995;21:180–183.
8.
Wells AJ. Passive smoking as a cause of heart disease.
J Am Coll Cardiol. 1994;24:546–554.[Abstract]
9.
Steenland K. Passive smoking and the risk of heart disease.
JAMA. 1992;267:94–99.[Abstract/Free Full Text]
10.
Kawachi I, Colditz GA, Stampfer MJ, Willett WC, Manson JE,
Speizer FE, Hennekens CH. A prospective study of shift work and risk of
coronary heart disease in women. Circulation. 1995;92:3178–3182.
11.
Steenland K, Thun M, Lally C, Heath C Jr. Environmental
tobacco smoke and coronary heart disease in the American Cancer
Society CPS-II Cohort. Circulation. 1996;94:622–628.
12.
LeVois ME, Layard WW. Publication bias in the environmental
tobacco smoke/coronary heart disease epidemiologic literature.
Regul Toxicol Pharmacol. 1995;21:184–191.
