The Health

Consequences

of SMOKING

A PUBLIC HEALTH SERVICE REVIEW : 1967

U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE
           i,`. -, ' Public Health Service


Public Health Service Publication No. 1696

For sale by the 6uperluten~t of Dommsl t+3, us. oo- t RintiIlE omce
         we&bgton, D.C. 204W - Wee 60 -ta


The Federal Cigarette Labeling and Advertising Act of 1965 (Pub-
lic Law 89-92) requires that the Secretary of Health, Education, and
Welfare submit regular reports to the Congress on the health conse-
quences of smoking, together with any legislative recommendations
he may wish to make.
This 1967 Surgeon General's Report was pr&tred to provide the
Secretary and the public with a review of the research findings which
have taken place in smoking and health in the approximately 3% years
which have elapsed since the Surgeon General's Advisory Committee
issued its monumental 1964 report. Part I of this document was in-
cluded as part of the Secretary's 1967 Report which he sent to Congress
in July 196'7. Part II, which provides detailed discussions of the re-
lationship of smoking to specific diseases, is issued here for the first
time.

The 1967 report represents a review of more than 2,000 research
studies published since the 1964 report. These additional studies con-
firm and strengthen the conclusion of the Surgeon General's Advisory
Committee that: "Cigtlrette smoking is a health hazard of sutllcient
importance in the United States to warrant appropriate remedial
action."

In a separate section of this report, acknowledgments have been
made for the help of numerous scientists both within and outside the
Public Health Service, who participated in the preparation of this
report. These include the 10 distinguished scientists who made up the
Surgeon General's 1964 Advisory Committee, all of whom were kind
enough to review part I of the 1967 report before its publication. A
special word of thanks is due Leonard M. Schuman, M.D., one of the
1964 committee members, who advised the staff in the final editing of
the entire document.

SURGEON GENERAL.


Table of Contents

Part I. Current Information on the Health Consequences of
    Smolring-_-------------------------------------
      Introduction__-------------------------------
    Smoking and Overall Mortality- _ _ _ __ __ _ __ _ _ _ _ _
        Some Oeneral Considerations- _ _ _ _ _ ___ ___ __
    Smoking and Overall Morbidity-- _ __ __ _ _ _ _ _ _ _ _ _
    Smoking and Cardiovascular Diseases,,- _ _ _ _ _ _ _ _
    Smotig and Chronic B~onchopulmonary Dis-
           eases (Non-neoplastic) _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
     Smoking and Cancer--- _ _ _ _ _ __ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
     Other Conditiona and Areas of Research- _ _ _ _ _ _ _
      Cited References----- -----I------------------
II. Technical Reports on the Relationship of Smoking to
    Specific Disease Categories- _ _ _ __ __ _ __ _ _ _ __ _ _ _ _ _ _
    Chapter 1. Smoking and Cardiovascular Diseases-
        2. Smoking and Chronic Bronchopul-
          monary Diseases (Non-neoplastic) _
              3. Smoking and Cancer- _ _ __ __ __ _ __ _ __
         4. Other Conditions and Areas of Re-
             search--------------------------

1
3
7
11
19
25

29
33
39
41

43
45

87
125

179

V


Acknowledgments

Responsible for the preparation of this report was the National
Clearinghouse for Smoking and Health, Daniel Horn, Ph. D., director.
Staff director for this report was Albert C. Kolbye, Jr., M.D., M.P.H.,
LL.B.

The professional staff has had the assistance and advice of a number
of experts in the scientific and technical fields in and outside govern-
ment. The staff gratefully acknowledges their contributions, often
made at considerable sacrifice of time from their own professional
duties. Although space does not permit a listing of all those who have
participated in this project, the staff wishes to express appreciation
for their cooperation and help. Special thanks are due the following:
hNAHT1, FBAITC~S R., D.V.M, PH. D.-Chief, Virology and Rickettaiologs
Branch, Extramural Program, National Institute of Allergy and Infectious
Dra~aesq National Institutes of Health, Bethesda, Md.
AMES, BBUCE N., M.D.-Laboratory of Molecular Biology, National Institutes
of Health, Bethesda, Md.
hEaD, WILLTAM P., M.D.-Medical consultant, Stroke Section, Heart Disease
Control Pro&m, National Center for Chronic Disease Control, U.S.P.H.S.,
Arlington, Va.
Aunns~on, Oecq M.D.-Senior medical investigator, Veterans Administration
Hospital, East Orange, N. J.
AXEUOD, DA=, M.D.-Medical consultant, Laboratory of Biology of Viruses,
National Institutes of Health, Bethesda, Md.
Am, Srnr~nrv M., M.D.-Dire&or, Cardiopulmonary Laboratory, Saint Vin-
cent's Hospital and Medical Center of New York, New York, N.Y.
AYEW, W= R., M.D.-Medical of&X& Heart Disease Control Program, Na-
tional Center for Chronic Disease Control, U.S.P.H.S., Arlington, Va.
Bmena, JOHH J., M.D.-Head, Department of Otolaryngology, Evanston Hos-
pital, Evanston, Ill.
BEBENDES, Hews, W., M.D.-Chief, National Institute of Neurological Diseases
and Blindness, Perinatal Research Branch, National Institutes of Health,
Bethesda, Md.
Bnao, Connon W;-`Statistician, Operational Studies Section, Cancer Control Pro-
gram, National Center for Chronic Disease Control, U.S.P.H.S., Arlington, Va.
Bsa~~nna, Ronmw, M.D.-Director, oface of Director of Research, National Heart
Institute, National Institutes of Health, Bethesda, Md.
BIBG, RIO- J., MD-Professor and chairman, Department of Medicine,
Wayne State University, Detroit, Mich.
BLEBE, STIJA~~ R, MD.-Medical consultant, Heart Disease Control Program,
National Center for Chronic Disease Control, U.S.P.H.S., Arlington, Va.

VII


BOBEN, HOUS, M.D.-Clinical investigator, Veterans A-Uin Hospital,
Denver, 62010.
CABBO& BENJAMIN E.-Biometric Bknch, National Cancer Institute, National
Inetitutea of Health, Bethesda, Md,
CHADWICK, DONALD IL, M.D.-Director, National Center for Chronic Dkaae
Control, U.S.P.H.S., Arlington, Va.
DE LA PUEITTIZ, Joema L.+hief, statistical methods, Cancer Control Program,
National Center for Chronic Disease Control, lJ.S.P.&S.. Arlington, Va.
DEYKIIT, DAXIZL, M.D.-Assistant proteseor of medicine, Harvard Medical Scholl,
Boston, Masf3.
DOBBS, GEOFCO~ M.D.-Aesociate chief. Dlvlalon of Sclentitl~ Ophio~, Eweral
Trade Commission, Washington, D.C.
DOYLE, JO~EPE, M.D.-Dir&or, Cardiovascular Health Center, Albany Medical
College, Union University, Albany, N.Y.
~ETMAH, NICOLAS J., M.D.-Profmr emerlhm of obatetrl~ Johns Hopldna
Hoepital, Woman's Clinic, Baltlmore, Md.
EPSTEIN, ~lcBIC!K H., M.D.--f-r, University of Mlcbigan School of Pt&llc
Health, Department of Epidemiology, Ann Arhor, AXich.
P~ELZOE, 8. PAUL, Jr., M.D.-Deputy chief, Heart Dlaeaae Control w Na-
tional Center for Chronic Disease Control, U.S.P.ES., Arllngbn, Va
EVANS, B~BEBT, Ph. D.-Department of sodology, University of Wisconein,
Madison, Wis.
FALK, HANS L., Ph. D.-Associate scientifk dlreetor for carcinogenesb, National
Cancer InstLtute, Natlonal Institutes of Health, Bethesda, Md.
Fmurxs, BEXJAMI~J G., Jr., M.D.-Professor, Deperbnent of Physiology, Harvard
School of F'ubllc Health, Harvard University, Boston, Masc.
Fox, BE~R~BD H., Ph. D.-Acting Chief, Experimental -Branch,Injnry
Control Program, National Center for Urban and Industrial Health, U.S.P.H.S.,
Arlington, Va.
Fox, SAHUEL M., III.,. M.D.Ahlef, Heart Disease Control Program, National
Center for Chronic Disease Control, U.S.P.ES.. ArRqbn, Va.
GIITLESOHN, ALLAN, Ph. D.-Professor, Johns Hopkins gob001 of P&c Health
and Hygiene, Johns Hopkins University, Baltimore, Md
GOLD, B~XALD J.-Statistician, Operational Stndies Section, Cancer Control Pro-
gram, Na,tional Center for Chronic Disease Control, U.S.P.HB., kiington. Va.
H~SZEL, WILLIAM M.-Chief, Biometry Branch, National Cancer Institute,
National Institutes of Health, Bethesda, bfd
mm, Max, Ph. D.-Assistant chief, Biometrics Besear& Branch, National
Instktntea of Health, Bethesda, Md.
HAMMOXD, E. Cm, SC. D.-Vice president., epidemiology and statistical IX+
sea&b American Cancer Society, New York, N.Y.
HA~ELL, WILLIAM L, Ph. D.-Physical activity consultant, Heart Disease Con-
trol Program, National Center for Chronic Disease Control, U.S.P.H.S., Arllng-
ton, Va.
HAYES, RICHAR.D, D.D.S.-Assistant to the chief, cancer detection. Cancer Control
Program, National Center for Chronic Disease Control, U.S.P.H.S., Arllnq-
ton, Va.
HEIXZELXAN, F&D, Ph. D.--Research peyeholagbt, Heart Disease Control Pro-
gram, Natfonal Center for Chronic Disease tints& U.S.P.ES.. Arlington, Va.
HESS. CATHERINE B., M.D.-Assistant to the chief, Cancer Control Program, Na-
tional Center for Chronic Disease Control, U.SS,H.S., Arlington, Va.
HIGQINS, I. I. T., M.D.-Professor, University of Michigan School of Pnhllc
Health, Department of Epidemiology, Ann Arbor, Mlch.


HO~FXAX~, D~TEICJH, M.D.-Associate member, environmental carcinogenesis,
Sloan-Kettering Inatltute for Cancer Research, New York, N.Y.
IMBODEN, C. &, Jr., M.D.-Chief, (&ronic Re8piratory Disease Control Frogram,
National Center for Chronic Dleease `Control, US.P.Hd., tilington, Va.
IBXBANT, Ar.aan~ P.-Uhief, Epidemiology and SurveilMnce Branch, Injury
Control Program, National Center for Urban and Industrial Health, U.W.P.H.S.,
Arlington, Va.
KANNEL, WISXJAM B., M.D.-Associate medical director, National Heart Institute,
Harvard Medical School, Boeton, Ma&a
KENNEB, HAIEZS, M.D.-Medical c&k&ant, Heart Ditveaae Dontrol Program,
National Center for Chronic Disease Control, U.S.P.H.S., Arllngton, Va.
KOOLBYE, SUBAX~AE M+Sclentiat, Chevy Chase, Md.
Korxx, Pam, M.D.-Director, National Environmental Health Sciences Center,
Research Triangle Par& N.C.
Krkmox& Dw E.-Statl&ician, Biometrics Section. Natlonal Heart Institute,
National Institutes of Health, Beth&a, Md.
LANDAU, EMANUEL, Ph. D.-Statistical advisor, OlIlce of the Director, National
Center for Air `Pollution Control, U.S.~P.ES., Washington, D.C.
LEQAT~B, Mmvrxv S., M.D.-Chief, Cell Biology Branch, Division of Nutrition,
Food and Drug Adminletration, Washington, D.C.
LEMAISTBE, CHABLKS A., M.D.-Vice chancellor of health affaire, Otllce of the
Chancellor, University of !kxas, Austin, Tex.
LILXEHFELD, ABMHAY, M.D.-Professor, Johns Hopkins School of Hygiene and
Public Health, Baltimore, Md.

LONOIN, Hmwwr, M.D.-O&X of associate director for collaborative studies,
National Heart Institute, National Institutes of Health, Bethesda, Md.
LOUDON, R. G., M.D.-Profeeeor, Department of Internal Medicine, University
of Texas, Da&la. Ta.
MABIAND, Rx- ,E., Ph. D.-Injury Control Program, National Center for
Urban and Industrial Health, U.S.P.H.S., Arlington, Va.
MoL~Ax, Roes, M.D.-Pro-C-r of medicine (pulmonary disease), Emory Uni-
versity, School of Medicine, Atlanta, Ga.
MOBBISON, BAYA~~ H., Ph. D.-Ofllce of the Director, National Cancer Institute,
National Institutes of Health, Bethesda, Md.
MOUNT, FBANK W., M.D.-Deputy chief, Ohronic Respiratory Disease Control
Program, U.S~P.HS., Arlington Va.
MUBPHY, EDYOND A., M.D.-Associate professor, University of Colorado Medical
Center, medicine and biostatietics, Denver, Cola.
PETQLBorv, WILLXAX `F., M.D.--chief, Obstetrics and Uynecolopy Service, USAF
Ho&al Andrews, MSHCB, Andrewa Air Force Basf?, Washington, D.C.
PETTY, THOMAS L., M.D.-Assistant professor of medicine, University of Colo-
rado Medical Oenter, Denver, Colo.

Romxe, Moxrox-chief, program evaluation and project design, Heart Disease
Control `Program, <National Center for Chronic Dlaeaae Control, U.S.P.H.S.,
Arlington, Va.
Eoss, WILLIAM L., M.D.-Chief, Cancer Control Program, National Center for
`Chronic Disease Control, U.S.P.H.S., Arlington, Va.
SCHUYAN. Lxor?~an M., M.D.-Professor of epidemiology, University of Minne-
sota, School ot Public Health, Mlnneapolie, Mlnn.
%2HWAmz, J. Tnxononr., M.D.-Se&on head, Epidemiology Branch, National
In&it&e of Neurological Diseases and Blindness, National Institutes of Health,
Bethezda, Md

Ix


SHBAB, MUBBAY J., Ph. D.-Special advisor, Once of &he D&&or, National
Cancer Institute, National Imt&ut.ea of Health, Betk%b, Md
SIBEL, JAM= S., M.D.-Chief, Field Staff, CoonlinaUon and Development 8ection.
Heart DBase Control w, National Center for Chronic Dlseatx an-
U.S.P.H.S., Arlhgton, Va
STEIN- WILLXAx, M.D.-Medical o5ker. Heart Dleeaee (h&r01 Prosrmb Na-
tional Center for Ohrouk Disease Control U.S.P.H.S, ArIingbIb Vk
&BONO, JACK, M.D.-airman of Deparbaent of Pathology, Ii4mwaM state
University, Sclmol of Medicine, New Orle!am#, Ii
THO& THOMAS J.-Stati&lclan, Heart Dlmxwe Control Program, National Center
for Chronic Disease Control, U.S.P.ES.. Arlingkm, Va
UNDEBWOOD, PAUL,  M.D.- A.sUtant professor of ohste&rics and g~necolfH%Y,
University of SoutI~ Carolina MedicsI Se&& went of (Bobtrim and
Gynecology, Charleston, 8.0.
WESTUBA, EDWIR, M.D.-Chief, Applied Phyhlogy Iaboratory, Heart Diseaee
Control Program, Nbbml Center for Chronic Diaeam Control, U.S.P.H.S.,
Arlhngton, Va.
WHITE, EZIJAH L.-A&g Director, Division ai Health Interview St&bt&
National Ceuter for Health Statistics, U.S.P.H.S., Wahhgb, D.C.
WOOLSEY, TH~DOM D.-`Deputy director, O&e d the Center Dhector, National
Center for Health Statietlca, U.S.P.&III, Washington, D.C.
WYRDEB, E~NBST L., M.D.-Associate member, Sloan-Kettering Institute for !kh-
nology, New York, N.Y.
YAKMOLINSKY, ~CEAEL, M.D.-tid chemist, Ircaborntiry d ~Ohcuhr
Biology, National Infkitutea of Health, Beth- Md
ZUKEL, WILLIAM J., MD.-Aseociate Dkeetor for Cdlabomtlve Studies, National
Heart Institute, National Inatltutes of Health, Bethesda, Md
The following professional staff of the National Clearinghouse for
Smoking and Health contributed to the preparation of this report:
Robert F. Clarke, Ph. D., Emil Con-in, Bobert S. H&hings, Selwyn
Waingrow, and David G. Wember, M.D.

X


PART 1

Current Information on the
Health Consequences of
         Smoking


Introduction

I n January 1964, an Advisory Committee appointed by the Surgeon
General of the Public Health Service issued its report (16) on the
relationship between smoking and health.* The conclusions of that
&nmittee were summed up in the sentence: uCigarette smoking is a
health hazard of sutllcient importance in the United States to warrant
appropriate remedial action."
In the 3% years since the publication of that report, an unprece-
dented amount of pertinent research has been completed, continued,
or initiated in this muntry and abroad under the sponsorship of
governments, universities, industry groups, and other entities. This
research has been reviewed and no evidence has been revealed which
brings into question the conclusions of the 1964 report. On the con-
trary, the research studies published since 1964 have strengthened
those conclusions and have extended in some important respects our
knowledge of the health consequences of smoking.
The present state of knowledge of these health consequencB8 can,
in the judgment wf the Public Health Service, be summarized as
follows :

1. Cigar&a smokers have substantially higher rates of death
and disability than their nonsmoking counterparts in the popu-
lation. This means that cigarette smokers tend to die &, earlier
ages and experience more days of disability than comparable
nonsmokers.

2. A substantial portion of earlier deaths and excess disability
would not have occurred if those affected had never smoked.
3. If it were not for cigarette smoking, practically none of the
earlier deaths from lung cancer would have occurred; nor a sub-
stantial portion of the earlier deaths from chronic bronchopul-
monary diseases (commonly diagnosed as chronic bronchitis or
pulmonary emphysenra or both) ; nor a portion of the earlier
deaths of cardiovascular origin. Excess disability from chronic
pulmonary and cardiovascular disectsss would also be less.

o ?????o? and Health. Report of the Advisory Cmnmittee to the Surgeon
~~~1 of the Public Health Service." It la frequently r&err& to in t& mann-
SeriPt a8 "the SW General'8 1964 Report."

3


4. Cessation or appreciable reduction of cigars& smoking
could delay or avert a substantial portion of deaths which occur
from lung cancer, a substantial portion of the earlier deaths and
excess disability from chronic bronchopulmonary diseases, and a
portion of the earlier deaths and excess disability of cardiom-
cular origin.

NATURE OF RECENT RESEARCH FINDINGS

Since the Surgeon General's Report was published in January 1964,
there has been a proliferation of additional studies and reports on
smoking research. In the 12 years preceding that report, some 3,000
articles were published reporting research; since 1964, there have been
more than 2,000 additional studies.

These studies have helped to clarify the role that age plays in the
relationship of smoking to health ; the similarities and diiIerences in
the ways in which men and women are affected by smoking; and the
influences and effects of stopping smoking, particularly in the case of
lung cancer where there is significant data to show thst sharp redue
tions in lung cancer deaths follow closely reductions. in cigarette
smoking. The studies also suggest the importance of a variety of
measures of exposure ; add substantial new information on the magni-
tude of the morbidity problem associated with smoking; and provide
more adequate data upon which to base estimates of the magnitude
of the mortality problem.
Historically, concern about the effects of smoking began with ob-
servations of the extremely high frequency with which lung cancer
patients were identified as cigarette smokers. These observations took
on a fuller meaning with the first publication of the prospective studies
in 1954 when higher overall death rates among cigarette smokers
were identified. The rates were found to exceed the difference that
could be accounted for by lung cancer alone. Until that time, the
possibility remained that although more cigarette smokers appeared to
suffer from lung cancer, if there were no significant excess overall
mortality, some other cause or causes of mortality would have had to
be underrepresented among cigarette smokers.

The Surgeon General's 1964 Report concluded that cigarette smokers
do have higher death rates than their nonsmoking counterparts. Thii
has changed the emphasis of the present problem away from the ques-
tion "does cigarette smoking cause diiP' to the more precise
questions of :
    1. How much mortality and excess disability are associated with
smoking?

4


    2. How much of this early mortality and excess disability would
not have occurred if people had not taken up cigareti smoking?
  3. How much of this early mortality and excess disability
could be averted by the cessation or reduction of cigarette
SlllOkillg?
  4. What are the biomechanisms whereby these effects take place
and what are the critical factors in these mechanisms?
To answer these questions one must not only study the details of
the relationship of ovdl mortality with cigarette smoking, one must
also turn to the specific causes of death and disability and to other
kinds of evidence.
The research carried on since 1964 is of three principal varieties :
Epidemiological studies, especially those which involve surveys of
large portions of the population ; a health survey which has revealed
new information about the relation between smoking and illness; and
a vast amount of experimental, clinical, pathological, and behavioral
research which adds to the understanding of the precise ways in which
smoking affects the body, plus other closely related or peripheral
information.
In the area of morbidity or `illness, the primary addition to our
knowledge is from "Cigarette Smoking and Health Characteristics,"
a report (16) of the National Center for Health Statistics on the
frequency of illness among smokers and nonsmokers in a large proba-
bility sample of the U.S. population. Regarding epidemiologioal data,
new reports from four of the major population studies have been
published since 1964 :
  1. The Dorn study of smoking and mortality among U.S. vet-
  erans (18).
  2. Hammond's study on smoking in relation to the death rates
  of 1 million men and women in 25 States (11).
  3. The Doll and Hill study on the mortality of British physi-
  cians in relation to smoking (8,&M).
  4. A Canadian Smoking and Health Study of Canadian pen-
sioners, including veterans and dependents (1).
The principal features of the additional data provided by these
four studies are.: (1) The extension of the time period of followup,
(2) the additional data available for specific age groups among men,
and (3) the inclusion of substantial data on women. In all, the pro-
spective study reports now available are based on more than 108,000
dwths, an increase of about 43,000 deaths over the 65,023 summarixed
in the 1964 report. About 19,960 of these additional deaths were among
women.


THE NATURE OF THIS REPORT

This report which provides a summary of current information on the
health consequences of smoking, is based on the review of the research
reports which have become available since the study of the Surgeon
General's Advisory Committee was releasexl. Public Health Service
staff members consulted the literature and requested additional infor-
mation or interpretations of the published data from the research
scientists when needed. During this review a complete bibliography,
containing some 5,766 citations, was compiled; it is .now in manu-
script form and will be published shortly (19).
The advice and comments of experts within the Public Health Serv-
ice, particularly the Bureau of Disease Prevention and Environmental
Control and the National Institutes of Health, as well as of specialists
outside the Public Health Service, were solicited especially on matters
involving judgment and evaluation.
The general criteria used by the Surgeon General's Committee have
been followed. First, epidemiological data were evaluated to determine
whether an association exists. In judging the significance of the as-
sociation, its consistency, strength, specificity, temporal relationship,
and coherence were utilized. The convergence of evidence from animal
experiments, clinical and autopsy studies, and population studies re-
mains the essential basis for evaluation of the significance of the
associations identified.

This report presents, under the following headings, the major find-
ings of research studies published in the past 3 to 4 years :
1. Smoking and Overall Mortality.
2. Smoking and Overall Morbidity.
3. Smoking and Cardiovascular Diseases.
4. Smoking and Chronic Bronchopulmonary Diseases (Non-neo-
    plastic).
5. Smoking and Cancer.
  6. Other Conditions and Research Areas.
Each of these sections is introduced by pertinent conclusions from
the Surgeon General's 1964 Report, which are followed by discussion
and conclusions of the present study.


Smoking and Overall Mortality

   CONGLIJNONS OF TEE SURGEON G ENElrAL's 1934 RsPoRT

CIGARETTE smoking is associated with a 70-percent increase in
the age-spe.cXc death rates of males, and to a lesser extent with in-
creased death rates of females. The total number of excess deaths
causally related to cigarette smo -II0 in the U.S. po ulation cannot
be accurately estimated. In view of t  continuing 811 if mounting evi-
dence from many sources, it is the judgment of the Committ.sc that
cigarette smoking contributes substantially to mortality from certain
specific diseases and to the overall death rate.

hi In general, the greater the number of cigarettes smoked daily, the
% her the death rate. For men who smoke fewer than 10 cigarettes
a ay, according to the seven
all causes is about 40 percent tl respective studies, the death rata from

who smoke from 10 to 19 ci   `gher than for nonsmokers. For those
        %T rettes a day, it is about 70
than for nonsmokers ; for t ose who smoke 20 to 39 a cir rcent higher

hi                          y, 90   cent
her; and for those who smoke 40 or more, it is 120 percent
&!                  KY?
igarette                       `gher.
     smokers who stopped smoking before enrolling in the.
seven studies have a death rate about 40 percent higher than non-
smokers, as against `70 percent higher for current cigarette smokers.
Menwhobegansmo'
     9
death rata than those w before age 20 have a substantially higher
          o began after age 25. Compared with non-
smokers, the mortality risk of cigarette smokers, after adjustments for
differences in age, increases with duration of smoking (number of
years), and is higher in those who stopped after age 55 than for those
who stopped at an earlier age.

In two studies which recorded the degree of inhalation, the mortality
ratio for a given amount of smoking w&s greater for inhalers than for
noninhalers.
The ratio of death rates of smokers to that of nonsmokers is hi  est
at the earlier ages (44-50)          %I
with increasing age.    represented in these studies, and dec *  es

Possible relationships of death rates to other forms of tobacco use

were also investi  ted
than 5 cigars a r  * * *. The death rates for men smoking less
       ay are about the same as for nonsmokers For men

Smoking more than 5 ci T rs daily death rates are slightly higher.
There is some indication t at these higher death rates occur  rimaril
in men who have bean smoking more than 30 years and w o i inhd
the smoke to some d
if at all hi her than or nonsmokers, even for meu who smoke 10 or
  ifll   Y . The death rates for pipe smokers are little

more pipe
30 years.  s a day and for men who have smoked pipes more than

271-224o-67-2                           7


CURRENT INFORMATION, 1967

The primary addition to knowledge in the nreas of smoking and
overall mortality comes from the four major population studies. Ad-
ditional periods of followup have provided a broader base from which
it .becomes possible to estimate the excB8s deaths related ,to cigarette
smoking in the U.S. population and from which firmer conclusions
may be drawn as to the role of various exposure factors in the associa-
tions found.

The contributions since 1964 of each of the four population studies
to the relation of smoking and overall mortality, as summarized by the
authors, are set forth below.

&tTJlY OF U.S. VETERANS

  (An 854 year followup of 293,658 persons holding U.S. Government
  life insurance polides. Commonly referred to as the Dom Study after
  the late Dr. Harold F. Dom. The most recent report is by Kahn (IS).)
"* * * the increased mortality risk associated with cigarette smok-
ing was found to be higher in the more recent calendar time period
than in khe initial years of the study.
"* * * mortality ratios of current cigarette smokers compared with
those who have never smoked are 1.7 for death from all causes, 10.9
for lung cancer, 12.2 for ssnphysema without bronchitis, and 1.6 for
coronary heart disease. Paralysis agitans was the only cause of death
associated with significantly lower mortality for smokers than for
nonsmokers.

"For all categories of current smokers, risk was related to amount
smoked. The risk for cigarette smokers was much greater than that for
pipe or cigar smokers. Current smokers of cigarettes, cigars, or pipes
experienced a mortality risk significantly greater than that for non-
smokers if they smoked more than four pipes or four cigars daily or
more than an occasional cigarette.
"There was a positive relationship between duration of cigarette
smoking and mortality risk from all causes of death for at least some
classifications of smokers,

"* * * probabilities of death for ex-smokers of cigarettes revealed a
downward trend in risk as duration of time discontinued increased,
when other variables--age began smoking, amount smoked, and cur-
rent age-were controlled * * *. The data can be regarded as evidence
against the constitutional hypothesis."
Calculations are presented to note that observations made during
the study suggest the possibility that data from respondents (those
who answered the smoking questionnaire) may in fact underestimate

8


the risk associated with smoking. The Surgeon General's 1964 Report,
had considered the possibility that di&ences between respondents
aud nonrespondents to the questionnaire might have introduced a
bias and had attempted to calculate a maximum estimate of that
bias.

STUDP OF MEN AND WOIKICN IN 25 STATIW

(This report is baaed on 3,764,671 Wrson-years of experience and 43,!2!21
deatha occurring among l,OQ3,ZZQ eubject8-M ,668 men and S.3,671
women-between the ages of 35 and 34 from October 1.1969. to Feb-
ruary 16,lQ60, when they enrolled in a proepe&ve study and answered
detailed queetionnairea including questions on their smoking habits.
Hammond. (II) .)

"Death rates of both men and women were higher. among subjects
with a history of cigarette smoking than among those who never
smoked regularly.

"Death rates of current cigarette smokers increased with number of
cigarettes smoked per day and degree of inhalation.

"Death rates were higher among current cigarette smokers starting
the habit at a young age than among those starting the habit later in
life. Among both men and women, the difference between the death
rates of cigarette smokers and nonsmokers increased with age.

"Among men, ,the death rates for ex-cigarette smokers were lower
than for men currently smoking cigarettes when they enrolled in the
study. Death rates of ex-cigarette smokers decreased with the length
of time since they last smoked cigarettes.

"* * * Total death rates and death rates from most of the common
diseases occurring in both sexes were higher in men than women,
were higher in men who never smoked regularly than in women who
never smoked regularly, and were far higher in men with a history
of cigare6t.e smoking than in women with a history of regular cigarette
smoking.

"The difference ,between the death rates of subjects with a history
of cigarette smoking and subjects who never smoked regularly was
far greater among men than women. Female cigarette smokers (as
a group) have been far less exposed to cigarette smoke than male
cigarette smokers of the same ages, as judged by number of cigarettes
smoked per day, degree of inhalation, and the number of years they
have smoked. Many female cigarette smokers smoke only a few
cigarettes a day, do not inhale, and have been smoking for only a
few years; their death rates are about the same as the death rat.4~ of
women who never smoked regularly."

STUDY OF BRITISH P~~~CIANS

(The mortality of nearly 41,000 men and women in the medical profes-
sion in the TJnH.4 Kinflom has been followed for I.2 yeara During the

9


tit 10 yeara 4,697 of the men and s&B ai the women died. These deaths
were analyzed in relation to smoking habits reported by doctors in reply
  to a questionnaire sent to them in 196l-both sexes-au d again in lOti?,
  men, and 1090, women Doll and Hill (8, 9).)
`;* * * An association with smoking is found, in differing degrees,
in men for seven causes of death ,[which accounted for 39 percent of
the death rate]-namely, cancer of the lung, cancers of the upper
respiratory and digestive tracts, chronic bronchitis, pulmonary tuber-
culosis, coronary disease without hypertension, peptic ulcer, and
cirrhosis of the liver and alcoholism. No association is found with the
remaining 61 percent of the death rate, and this includes such major
causes as other forms of cancer, cerebrovascular accidents, hyperten-
sion, myocardial degeneration, suicide, and accidents.
"In women, the few deaths at present available show an association
only between smoking and cancer of the lung.
U* * * If the excess deaths in smokers under the age of 65 years
from (a) cancer of the lung, (6) chronic bronchitis and emphysema,
(c) coronary thrombosis without hypertension be taken as attributable
to their cigarette smoking, then the total mortality from all causes at
ages 45-64 years is increased thereby by approximately 50 percent."
The report states: "One of t.he striking characteristics of British
mortality in the last half-century has been the lack of improvement
in the death rate of. men in middle life. In cigarette smoking may lie
one prominent cause."

STUPY OF CANADUN PENEIONPXS

(The purpose d the study was to investigate the relationships between
residence, mtion, smoking ~habits, and mortality from chronic
Waaes .@cularly lung cancer. It was initiated by a que&ionndre
which was sent to Canadian veteran pension recipients doriug the
period September 1955 through June 196g.

Returns from ?S#OO men, and 14,000 women, mostly widows, were
analped. The men were mainly World War I and World War II vet-
erans, but some Boer War and Korean War veterans, as well aa some
non-veteran pension recipients were included. The age of most of the
men at the beginning of the study ranged from 30 to 90 years and the
distribution was characterised by the ages of men eligible for service
in the two World Wars.

For each respondent dying between July 1. 1956, and June 30, 196%
the cause oi death was related to information on his questionnaire
atint age, history of emoking habits, residence and occopation.
Among the respondents during the 6 years of followup there were Q&l
deaths of males, and l,?fM deaths of females which were analyaed
  (11.1
"Current cigarette smokers had a death rate for overall mortality
54 percent higher than that of nonsmokers * * * Ex-cigarette smok-

10


ers had a comparatively lower rate, which was still 36 percent above
the rate for nonsmokers * * * Men smoking combinations of ciga-
rettes plus cigars and/or pipe also had elevated death rates for overall
mortality, but these were not elevated to the same extent as those of
men smoking only cigarettes.
"The death rates for overall mortality of pipe smokers and cigar
smokers were not appreciably different from those of nonsmokers.
"For cigarette smokers as compared to nonsmokers, overall mor-
tality ratios were elevatd after 5 years of smoking at any time in
their life and remained elevated as long as they amtinued to smoke
cigarettes.

"Male current cigarette smokers who inhaled had a death rate for
overall mortality 52 percent higher than that of those who did not
inhale.

"An urban/rural comparison was made between males of equivalent
cigarette smoking habits and nonsmokers. It was found that the
death rate for overall mortality of urban dwellem @rsons with
a history of 5 years or more of city residence) was 12 percent higher
than that for rural dwellers of comparable smoking habits.
"Respondents were classified into occupational groups based on
their history of occupation. No evidence was found in this study of
clear-cut associations between cause of death and occupation. Further,
occupation did not appear to modiQ the e&ab%shed association of
cigarette smokers with death rates in ~XCCZB of those of nonsmokers."

SOME GENERAL CONSIDERATIONS

The problem of how best to measure the relationship between smok-
ing and mortality has been discussed in the Surgeon General's 1964
Report as well as in some of the proqective study reports. &4 the
amount of data available increases, the person-v of observations
in the many population subgroups that are worth examining increases
so that stable rates may be computed and compared. A brief discussion
of three measures of comparison available and their utility seems
desirable as confusion frequently arises over these measmes.
  1. Mortality Ratios: Obtained by dividing the death rate for
a classification of smokers by the death rate of a comparable
  group of nonsmokers.

2. Differences in Mortality Rates: Obtained by subtracting
from the death rate for smokers, the death rate of a comparable
group of nonsmokers.

3. Excess Deaths: Obtained by s&ra&ng from the number
of deaths occurring in a group of smokers, the number of deaths

11


which would have occurred if that group of smbkers had ex-
perienced the same mortality rates as a comparable group of
nonsmokers. In the example which follows this has been reported
as a percentage of all deaths in the appropriate age group.
Table 1 presents in summary form all three measures for five age
groups of men from both the U.S. veterans study and Hammond's
study and for the same age groups of women from the latter study.
The statistics were derived from the cited publications to provide
reasonable comparability and may vary slightly from the Bgures
combined in other ways. Also it should be noted that the age groups
are not defined identically and the experience reported covers some-
what different time periods. The smoking group analyzed is "cur-
rent cigarette smokers," i.e., those who were smoking at the time of
enrollment into the study, and the comparison group is %ever smoked
regularly," i.e., those who had never been regular smokers of any
form of tobacco.

The nmnber of deaths in each age-sex group is given to indicate
the relative stability of the figures in that column. The data in the
veterans study are largely concentrated in age groups X5-64 and
65-74. In Hammond's study, age group 3544 is less stable than the
succesding groups both for men and for women.
1. Morta&y Rat&x-For men, these are at their highest in
age group 45-54, diminishing in each subsequent decade. In both
studies mortality ratios appear to be somewhat lower in the preceding
decade 35-44. However, with the smaller numbers of cases available
in that age group, it may be that selective factors contribute to the
fluding. For women the mortality ratios are much smaller than for
men, although the same pattern is suggested. In general, a mortality
ratio has been considered to reflect the degree to which a classiflca-
tion variable identifies or may account for variations in death rates.
As such, it is a measure of relative risk which indicates the importance
of that variable relative to uncontrolled variables-an indicator of
phi?&zl biologicaz 8ifpG-8.

2. Difftmncerr ila Mort&y Ratea.-These increase consistently
with increasing age in all three study groups, except for the oldest
age group in women where there is practically no difference in the
rates for smokers and nonsmokers. Differences between smokers' rates
and nonsmokers' rates are much smaller for women than for men,
as are the death rates themselves for men and women classified simi-
larly with respect to smoking. This measure reflects the added proba-
bility of death in a l-year period for the smoker over that for the non-
smoker. As such it is a measure of peraon.& health &g&@n.ct?, a means
for the individual to estimate the added risk to which he is exposed.

12


TABLE l.-Compariam of 3 nmmm+s of relatkhip betwem cigarette
smoking and ovem?~ death rates by age and 8ex a8 derived from W
major proepective 8tu4698 (11,13)'

U.S. VETNRANB: &N

   Total deaths __________ _____,
Death rates per 100,000:
  Never smoked regularly _______,
  Current cigarette smokers- _ _ _ _.
Mortality ratio * __________________.
Difference in death rates per
100,000 * ----_-_--------__-----.
Exceaa deaths as percentage of
totsl'-------------------__---_.

   Total deaths __________ ___ __.
Death rates per 100,000:
  Never smoked regularly _______.
Current cigarette smokers- _ _ _ _
Mortality ratio f _______ __ ___ _ ___ __.
DiSerence in death rates per
100,000'~~~____~~~~~________~~.
Excess deaths as percentage of
total'----______-_-_______-----.

HAMMOND WOMEN

   Total deaths ___________ _ ___.
Death rates per 100,006:
Never smoked regularly-- __ _ ___
Current cigarette smokers-----.
Mortality ratio * ____________ ______.
DSerence in death rates per
100,000~ _-_____________________
Excess deaths aa percentage of
total'-----_--_---------_-----.

383    366  13,840  17,550  1,932


127    264   1, fm  2# 411  6,214
232    723   1,819  4032  s, 471
1. 83    2 76    L 72    L 67   1.36


105    464    763   1,621  5257

  33    43     21     17     8

631  5,297


210    406
397    925
1. 89   228


187    519


33    33

4125  39968

9168  7, a63
4788  9,674
1. 51   123

1, 620  1,811

  13     4

727


105
186
1. 13


21


  5

Kg=

304
334
L26


  30


  9

3,915

698
333
1. 20

5,115

1,913
s=
L 17

146


4

316

2

r,l@

5,914
5,846
.99


  68


-----

48-k

65-74

76-84
---


3. Eacea Deaths aa a Percentqe of Total Death-h with mor-
tality ratios, this statistic appears to be highest in the age group 45-54
where it reaches 43 percent in one group of men and 38 percent in
the other. Hammond's data by B-year age groups show the highest
rate at ages 45-49, where it is 44 percent. Reviewing both study groups
it appears that for men between the ages of 35 aud 60 approximately
one-third of all deaths that occur are excess deaths in the sense that
they would not have occurred as early as they did if cigarette smokers
had the same death rates as the nonsmoking group. For women, the
percentage is much lower, reaching a peak of 9 percent of all deaths
in age group 45-54. It should be noted that this measure not only de;
pends on the differences in death rates between the smokers and the
nonsmokers, but also on the proportion of smokers in the group. Thus,
even with a large difference in rates between smokers and nonsmokers,
a population with very few smokers would have very few excess
deaths. This measure is therefore an indicator of the p&Z& hea.Zth
Bisnificymrce of the differences found since it measures the number of
people affected and therefore the magnitude of the problem for society
as a whole.

Once the magnitude of the excessis identified the problem becomes
one of determining (1) how much of the excess would not have oc-
curred if it had not been for cigarette smoking and (2) how much
would have occurred anyhow. It should be noted that much of the ex-
cess has already been identified as belonging in the first category. Of
the remainder, little of the excess has been clearly identified as belong-
ing in the second category-t.hat is, not caused by smoking. With most
of that remainder there is uncertainty as to the category in which it
belongs.

Studies involving smoking, whether epidemiological or ,behavioral,
have been concerned with measures of exposure to tobacco smoke. For
the most part, these studies have been restricted principally to the in-
dex of number of cigarettes smoked over a spe&ed period of time,
usually an "average day." The heavy reliance on numbers of cigarettes
alone as a measure has produced important findings but it has possi-
bly obscured others. The new reports on the prospective studies have
provided a substantial amount of data to support the concept that
many elements should entsr into an overall measure of exposure. Such
factors as age at beginning smoking, duration of smoking, and inhala-
tion have all shown some independent contributions to the overall
effect, along with numbers of cigarettes. A recent report (16) has at-
tempted to develop a more adequate measure of exposure in which
various individual components of dosage would be combined to form
compositescores.

14


A dosage score was developed as a function of the average number
of cigarettes smoked per day, the "tar" (smoke solids minus moisture)
rating of the brand of cigarette smoked, and the portion of the ciga-
rette actually smoked. In addition, questions on both depth aud fre-
quency of inhalation were developed. Normative data have been ob-
tained from a national survey sample of smokers. In general, although
the various measures reflecting exposure are interrelated, there are
many individuals with high exposure on one measure but low ex-
posure on another. Furthermore, there are sysbma& differences in
some of these measures of dosage between men and women, between
heavy and light smokers (by the usual criterion of numbers of ciga-
rettes) , etc. The existence of a dose-response relationship between ex-
posure to cigarette smoke and the risks most clearly associated with
cigarette smoking is now generally accepted.
Wynder .and 4Hoffmann (90) have shown in laboratory experiments
with animals that the tumorigenicity of cigarette smoke can be
reduced by alteration in the cigarette which reduces the "tar" and nico-
tine content. They use the term "indicator" for %r" and nicotine con-
tent (the two measures tend to be used jointly since when one is high
the other tends to be high unless the nicotine has been removed in
processing), or other measures which reflect this Qpe of relationship,
lacking the identification of specific agents which are responsible for
the effect. Bock, Moore, and Clark (8) have independently shown a
similar variation in carcinogenic activity of tobacco Yati' obtained
from different types of cigarettes.
The preponderance of scientific evidence strongly suggests that the
"tar" and nicotine content of cigarette smoke is a meaningful factor in
the measurement of dosage.

The cessation of smoking is, of course, an extreme example of the
reduction of dosage. Data from the prospective studies show a reduc-
tion in both overall mortality axid mortality from specific diseases
among those who have stopped smoking when compared with those
persons who continue to smoke. This finding has been somewhat ob-
scured by the fact that ill health is a frequent cause of giving up
smoking so that death rates and disability rates for ex-smokers as a
group tend to be high for an initial period of time following cessation.

In this connection, the Study of British Physicians shows that
among the total group of physicians in the &udy (smokers, ex-
smokers, and those who never smoked, combined) there was a reduc-
tion in the standardized lung cancer death rate from 0.69 per 1,000
in the first 5 years of the study (1951-56) to 0.64 per 1,000 in the sec-
ond 5 years of the study (1956-61). This reduction occurred during

16


the time when there was also a substantial drop in cigarette smoking
among physicians in general, and during the time that lung cancer
rates were risii in the male population of Great Britain. This situa-
tion is not unlike that of a controlled cessation experiment in which
the effect of giving up smoking is judged by the mortality results in
an entire population in which the giving up of smoking is common
as against another population in which it is not common. A more recent
report by Doll (7) suggests that this trend is becoming more marked
as the rate of smoking among British physicians decreases and the
length of the cessation period increases.
These Endings are shown in Table 2, which has been derived from
Doll's report (7). The lung cancer death rate among men in England
and Wales increased from 1.49 per 1,000 in the period 1954-57 to 1.86
per 1,000 in the period 1962-64, a rise of 25 percent. At the same time,
the lung cancer death rate for British physicians dropped from 1.09
per 1,000 in &he first period to 0.76 per 1,000 in the second period, a
reduction of 30 percent. This reduction in death rates from lung can-
cer among all physicians is larger than would have been anticipated
from examining only the experience of those physiciaus who had
stopped smoking before the study began and indicates that the ex-
perience of ex-smokers in prospective studies probably understates
the benefits of giving up smoking.
With these fmdings the case for cigarette smoking as the principal
cause of lung cancer is overwhelming. The reduction of rates experi-
enced in ex-smokers as compared with continuing smokers is clearly
shown in the case of lung cancer to be a reflection of a sign&ant
change in risk. Since the concern that selective bias might have ac-
counted for the earlier findings has been contraindicated, a stronger
case csn now be made for interpreting reduced rates of overall mor-
tality for those who give up smoking as also reflecting a direct ahera-
tion of risk compared to those who continue to smoke.
There are no adequate data to evaluate the benefit of reductions in
exposure that are more mode& than those achieved by complete ceesa-
tion, although it seems reasonable to assume that a substantial reduc-
tion in exposure is likely to be accompanied by some reduction in risk
relative to those who do not reduce their exposure.

16


TABLE 2 .--changes
sicians     in the lung canw death rate in male British phy-
   (age 36-84) compared wit% chunges in the &es f&r talc ma&
popu.?ation of England and Wales for 3 time G&sv& bebxcn 1964
and 1964 (7)

The period

1954to 1957___________________________________
1958tJo 1961------______-______________________
1962to 1964--------____--_____________________
Percentage change:

1st to 2nd period- __ _ ___ _ __ _ ___________ _____
2nd to 3rd period---- _____ -- ________________
lstto 3rd period---_________________________

+15
++a%

-24
-8
-30

17


Smoking and Overall Morbidity

T TEIE TIME of the Surgeon General's 1964 Report there was no
A information available on the overall disability associated with
smoking. To investigate the relationship between smoking and mor-
bidity, the National Center for Health Statistics of the Public Health
Service introduced questions about cigarette smoking into its National
Health Survey, beginning in July 1964. This Survey is a continuing
study conducted since 1957.

In carrying on this Survey, interviewers each year visit 42,000 fami-
lies (selected as a probability sample of the civilian, noninstitutional
population of the United States) and question them about illness, dis-
ability, and days absent from work ,because of illness, as well as the
nature of the illness. In the year ending in June 1965, they inquired
(after all other questions about health had been asked) about the smok-
ing habits of persons in the family who were 17 years of age or over.

The National Health Survey is concerned with three overall meas-
ures of the impact of illness.
1. Daya Loat Frcnn Work.- These are days absent from job or busi-
ness because of illness or injury. They apply only to those persons
who are currently employed and are therefore heavily concentrated in
age groups 17-64.
2. Bed Day&-These are days when the person is su5iciently ill or
disabled so as to spend all or most of the day in bed, either at home
or in a hospital. All days spent as a hospital patient are included.
3. Days of Restricted Activity.-These are days when a person cuts
down his usual activities for most of a day because of an illness or
an injury. Days lost from work because of illness and bed days are, of
course, counted as days of restricted activity. This represents the most
general measure of, disability available in the United States today.
Table 3 summarizes the findings in a form similar to that used for
summarizing the overall mortality utilizing three measures of mor-
bidity effect : Morbidity ratios, differences in rates, and excess days of
disability.

19


TABLE 3.-tZlnnpa&m of 3 mexuurea of relakhip between cigar&
smoking and 3 types of didiZity days bg age and 8cx as cikiuedfrom
the Nat&maZ Et&h &uvcg (16)

WOESLoss DAYS

E&hated total days (millions)----..
Rate: '

112   127    21    80    5s     4

  Never smoked cigarettea _______   3.4   5.6   9.8   4.5   5.3
  History of cigarette smoking----   4.4   8.5   9.8   6.5   6.9
Morbidity ratio *-- _______________   1.3   1.5   1.0   1.4   1.3
DBerence in morbidity rhea * I--- _ _   1.0   2.9    0   2.0   1.6
Excess days as percentage of total a-   20    28     0    18    11

RESTEICTED ACTIVITY Days

Estimated t&al days (millions)-----
Rate: 1

305   386   271   543   489   395

  Never smoked cigarettea _______  7.5  15.0  32.9  13.3  22.6   40.1
  History of cigarette smoking- _ _  10.6  22.9  37.9  17.8  25.3   44.8
Morbidity ratio *--- ______ _ _ _ _____   1.4   1.5   1.2   1.3   1.1    1. 1
DiiTerence in morbidity ratea I4--- _ _   3. 1   7.9   5.0   4.5   2.7    4.7
Excess days as percentage of total I-   23    28    8    14    5     2

BED DAYS

E&ii&xl total daya (millions)-----
Rate: '

111   118

Never smoked cigarettes _______  2.7   4.6
  History of cigarette smoking- _ _  3.9   6.9
Morbidity ratio I-- _ --_-----______   1.4   1.5
Difference in morbidity rates * 4--- _ _   1.2   2.3
Excess days as percentage of total I-   23    28

AhIn

T

17-44

46-M

Bsnlld
OVW

100


13.4
13.0
.97
-0.4
-1

5.0
:
:

210   168    146

5.4   8.0   15.1
6.7   9.2   15.2
1.2   1.1    1.0
1.3   1.2    0.1
10    6     0

B5aud
OVW

' DiU- ln hfmbldity Ii&a-itforbidifv rate for c&art& amokem minas morblditv rota for thuw who
twmbmob4d~df.w.

` Exceaa deatha among c@rette amokas (I.E., addltionnl days o[ dlmbfflty that omur among c@mtte
smokem prr yew dove thorn whkb would hme ocamed li amokexa had the name rated aa thm who nevs
smoked cigamttss). TUJ Is expmmmd a~ a percmm of oil diw&Uity dnys ooxmfng in that ale-m gronp.

DAYS LOST FROM WORK

For those with a history of cigarette smoking, classified by heaviest
amount smoked, the average number of days was 7 percent higher for
men and 15 percent higher for women who had smoked less than 11
cigarettes per day; 33 percent higher for men and 60 percent higher

20


for women who had smoked 11-20 cigarettes per day ; 48 percent higher
for men and 79 percent higher for. women who had smoked 21-40
cigarettes per day; and 33 percent higher for men and 140 percent
higher for women who had smoked more than 40 cigarettes per day.
The relationships expressed by all three measures are somewhat higher
among men aged 45-64 than among men aged 17-44, but lower among
women aged 45-64 than among women aged 174. In the survey year,
there were an estimated 399 million workdays lost in the United States
because of illness. A total of `77 million days, or 19 percent, were excess
workdays lost because of the higher rates which exist among persons
who have ever smoked cigarettes as compared to those who never
smoked. This excess loss is highest in men 45-64 where it represents
28 percent of all days lost.

BED DAYS

For those with a history of cigarette smokiug, class&d by heaviest
amount smoked, the average number of days was 10 percent higher
for men and 4 percent lower for women who had smoked less than 11
cigarettes per day ; 22 percent higher for men and 17 percent higher
for women who had smoked 11-20 cigarettes per day; 22 percent high-
er for men and 57 percent higher for women who had smoked 21-40
cigarettes per day; and 53 percent higher for men and 192 percent
higher for women who had smoked more than 40 cigarettes per day.
Relationships with smoking are higher for men than for women for
all three measures except for age 17-44 in which the d.ifTereuces in mor-
bidity rates between smokers and nonsmokers are about the same. For
the entire population 17 years of age and older there were an estimated
853 million bed-days in the survey year. A total of 88 million of these
days, or 10 percent, were "excess" days lost because of the higher rates
which exist among persons who have ever smoked cigarettes as com-
pared to those who never smoked. Excess days as a percentage of total
bed-days is highest for men aged 45-64, where it is 23 percent.

DAYS OF RESFRICTED ACTIVITY

For those with a history of cigarette smoking class&d by heaviest
amount smoked, the average number of days was 12 percent ,higher
for men and 4 percent higher for women who had smoked leas than
11 cigarettes per day ; 32 percent higher for men and 22 percent for
women who had smoked 11-20 cigarettes per day; 39 percent higher
for men and 43 percent higher for women who had smoked 21-40
cigarettes per day ; and 81 percent higher for men and 146 percent
higher for women who had smoked more than 40 cigan&.es per day.
Again rates are higher for men than for women in all three measures
except for age group 1744, in which differences in morbidity rates
are higher for women. There were an estimated 2,369 million such days


in the survey year; 306 million, or 13 percent, were excess days lost
because of the higher rates which exist among persons who have ever
smoked cigarettes as compared to those who never smoked. Excess
days as a percentage total restricted activity days was highest in men
aged45-64.
To help evaluate these general indices of morbidity as measured by
various kinds of disability days it is necessary to turn to the conditions
which are reported more frequently by cigarette smokers than by non-
smokers. Since these are either self-reports or reports made by a re-
sponsible member of the household for others in the household, the
diagnostic accuracy of the reports is obviously less than one could ob-
tain from direct medical examination. Nevertheless, the bulk of the
reports on chronic conditions reflect what a physician has previously
told the patient or the family with regard to a diagnosis of the
condition.
Chronic conditions (one or more) are reported by 11 percent more
of the men and 9 percent more of the women who have ever smoked
cigarettes than by those who have never smoked. cigarettes. This is
especially high in those who have reported their highest consumption
rate to have ,been over two packs a day (32 percent higher for men
and 43 percent higher for women). At the lower levels of consumption
the rates reported are 21 percent and 25 percent higher for those
smoking 21-40 cigarettes per day, but only 5 percent higher for men
and 7 percent higher for women for those smoking 11-20 cigarettes per
day and only 1 percent higher for both men and women who have
never smoked more than 10 cigarettes per day. The differences are
especially marked among present smokers of more than two packs per
day whose rate of reporting three or more chronic conditions is 73
percent higher for men and 143 percent higher for women than for
those who have never smoked cigarettes.
Applying differences in prevalence rates to the entire U.S. popula-
tion 17 years of age and over yields the estimate that there are approxi-
mately 11 million more cases of chronic illness annually than there
would be if all people had the same rate of~`sickness as those who had
never smoked cigarettes. A large portion of these are accounted for by
conditions classified as "chronic bronchitis and emphysema," "heart
conditions," "peptic ulcers," and "sinusitis." All but the last of these
have previously shown substantially higher mortality rates among
cigarette smokers. Si.nusitis,`being a nonfatal condition, has not been
identified in the studies of mortality previously reported. The "heart
condition" relationship is most marked in the category "arteriosclero-
tic heart disease including coronary disease."
The age-adjusted incidence rate of acute conditions for persons who
had ever smoked was 14 percent higher among men and 21 percent
higher among women than the rates for "never smokers." However,


particular caution must be taken in interpreting the results relating
specific acute conditions to cigarette smoking because of the relatively
large sampling error connected with the estimates for the several types
of acute conditions.

Since the National Health Survey is not a prospective study, it does
not identify the rate at which various types of morbidity develop in
comparable groups of smokers and nonsmokers, but reports the recent
existence of such disability. Therefore, the tidings are much more
significant when they support relationships previously identified than
when new relationships are identified. It should not be surprising that
causes of mortality which are associated with cigarette smoking have
a counterpart in disease or disability associated with smoking.
As the primary source of data in the United States on disability,
the Survey report, being based on a national probability sample,
provides a solid base for estimating the excess overall disability asso-
ciated with cigarette smoking.

HIGHLIGHTS OF CTJRRENT INFORMATION ON OVERALL
        MORTALITY AND MORBIDITY

1. The previous conclusions with respect to the association between
smoking and mortality are both confirmed and strengthened by the
recent reports. The added period of followup and analysis of deaths
of nonrespondents as well as of respondents in the Darn Study sug-
gests that the earlier reports may have understated the relationship.
2. More information is now available for specific age groups than
previously. A comparison of three ways of measuring the relationship
indicates that cigarette smoking is most important among men aged
45 to 54 both in terms of mortality ratios and exc855 deaths expressed
as a percentage of total deaths. Nevertheless, although both of these
measures decline with advancing age, the increment added to the
death rate, which reflects one's personal chances of !being affected,
continues to increase with age. For men between the ages of 35 and 59,
the excess deaths among currant cigarette smokers account for one
out of every three deaths at these ages. For women, with their lower
overall exposure to cigarettes, the comparable figure is about one
death out of every 14 at ages 35 to 59.
3. Women who smoke cigarettes show significantly elevated death
rates over those who have never smoked regularly. The magnitude
of the relationship varies with several measures of dosage. By and
large the same overall relationships between smoking and mortality
are observed for women as had previously been reported for men, but
at a lower level. Not only are the death rates for men who have never
smoked regularly higher than those for women who have never smoked

27l-3a4o-674                           23


regularly, but the effect of smoking as measured either by differences
in death rates or by mortality ratios is greater for men than for
women. At least part of this can be accounted for by the lower ex-
posure of female cigar&e smokers whether measumd by number of
cigarettes, duration of smoking, or degree of inhalation.
4. Previous .&dings on the lower death rates among those who
have discontinued cigarette smoking are confirmed and strengthened
by the additional data reviewed. Kahn's analysis of ex-smokers in the
U.S. veterans study-controlling for age at which they began smoking,
amount smoked, and current age-reveals a downward trend in risk
relative to those who continued to smoke as the duration of time dis-
continued increases. The British physician study, in which a downward
trend is reported in lung cancer death ra&s for the entire group
(smokers, ex-smokers, and those who never smoked, combined) along
with a very sharp reduction in cigarette smoking by the physiciaus, is
the beet available example of a controlled cessation experiment with
reduction of risks resulting from reduction of smoking. The Sndings
of this report support the view that epidemiological data showing
lower death rates among former smokers than among continuing
smokers cannot ,be dismissed as due to selective bias and that the bene-
fits of giving up smoking have probably been understated.
5. Cigarette smokers `have higher rates of disability than non-
smokers, whether measured by days lost from work among the em-
ployed population, by days spent ill in bed, or by the most general
measurdays of "restricted activity" due to illness or injury. Data
from the National Health Survey provide abase for estimating that in
1 year in the United States an additional 77 million man-days were
lost from work, an additional 88 million man-days were spent ill in
bed, and an additional 306 million man-days of restricted activity were
experienced *because cigarette smokers have hiiher disability rates than
nonsmokers. For men age 45 to 64,28 percent of the disability days
experienced represent the excess associated with cigarette smoking.

24


Smoking and Cardiovascular Diseases

   CONOLUkUONS OF m &JRGlWN G- `8 1964 Rnronr
Male cigarette smokers have a higher death- rate from coronary
artcry disesse than nonsmoking males, but it IS not clear that the
association has causal sign&ance.

CURRENT INMIRMATION, 1967

Important additional epidemiological information from five pros-
pective mortality studies confirms that cigarette smokers have sub-
stantially higher death rates from coronary heart disesse `than do
nonsmokers. This is true for `both men and women although the
relationships are less marked in women. Cigarette smoking also
markedly increases an individual's susceptibility to earlier death from
coronary disease. In general, mortality rates increase with increasing
amounts emoked.

Cessation of cigarette smoking is followed by a reduction in the
risk of coronary heart disease mortality relative to those who con-
tinued to smoke. Epidemiological evidence indicates that there is
little risk of coronary heart disease associated with cigar and/or pipe
smoking.
The Surgeon General's 1964 Report indicated a median mortality
ratio of 1.7 for current cigarette smokers, with a range from 1.5 to 2.0.
Additional evidence from the Hammond study (11) indicates that
young smokers between the sges of 45 and 54 have the highest mortality
ratios-three times as great for men, and twice as great for women if
they smoke 10 or more cigarettes per day, as compared with non-
smokers. In general, the mortality ratio shows the most marked in-
creases with increasing amount smoked for the ages under 65. While
the cigarette smokers older than 65 have lower mortality ratios than
those under 65, the public health significance of the relationship in
the older population is subetantial because of the large numbers of
people over 65 who die of coronary heart disease. Studies of U.S.
veterans (18)) Canadian pensioners (1)) British physicians (8,9, JO),

25


and California long&oremen (3) also provide extensive additional
information about coronary heart disease in male cigarette smokeIs ss
ccunpared to nonsmokers, supporting the above statements as they
pertain to men.

The study of British physicians (8, 9, 10) suggests that #male
cigarette smokers have the largest increase in risk for death certi-
fied to coronary thromboeis-a subcategory of coronary heart disease
describing acute coronary events,, frequently occlusive, causing rnp
cardid infarction. For that subcategory, the mortality ratio is also
largest for the younger age groups 35-54.

Prospective morbidity studies confirm the relationships between
cigarette smoking and carom-q heart disesse. These studies also
provide the opportunity to evaluate the effect of smoking independ-
ently and in combination with other known %sk factors," such as
high blood ~RW.UW and high serum cholesterol that are also impor-
tant in the pathogen&s of coronary heart disease. It has been demon-
strated that cigarette smoking not only operates as an independent
"risk factor" but that it may combine with other "risk factors" to pro
dues even greater effects on cardiovascular health.
Other types of evidence have also been presented to con&m the
epidemiologic evidence. Autopsy studies show the& cigarette smokers
have a much greater frequency of advanced coronary arteriosclerosis
than do nonsmokers. Clinical and experimental studies demonstrate
that smoking produces abnormalities of cardiovascular physiology
that may help to explain the mechanisms of haw, smoking may pro-
duce earlier death from coronary heart disease.

Human and experimental studies indicate that the nicotine ab-
sorbed from smoking may cause an increase in the myocardial tissue
demand for oxygen yet at the same time the carbon monoxide absorbed
from smoking may cause a decrease in the supply of available oxygen
from the blood necessary to meet the increased myocardial tissue
demand. Studies indicate that some persons who already have pre-
existing Coronary heart d&ease, not necessarily clinically obvious,
may be especially susceptible to the adverse physiological effects of
smoking. Evidence also indicates that important differences may
exist ,betwwn normal individuals and those with coronary heart dis-
ease in their ability to increase coronary Iblood flow to compensate for
increased myocardial tissue oxygen demand. Smoking apparxmtly can
accelerate thrombus formation of human blood, suggesting another
possible mechanism whereby smoking might increase the mortality
from coronary heart disease, especially those acute coronary events
certihd as "coronary thrombosis."
The convergence of many typee of eviden~pidemiological, ex-
perimental, pathological, and clinical-strongly suggests that ciga-
rette smoking can cause death from coronary heart disease. These

26


biomechanisms may help to explain why cigarette smokers have such
au increased risk of developing coronary !heart disease and of dying
from it.
An increasing amount of evidence has been accumulated in the past
few years relating the development of clinical cerebrovascular disease
to cigarette smoking. Most of this information has come from mor-
tality studies (17, 18), both retrospeotive and prospective, which
show that Iboth male and female smokers of cigarettes under the age
of 75, as compared to nonsmokers, have higher death rates from cere-
brovdar disease designated as the underlying cause of death on
their death certificates. This may abe especially true for younger ciga-
rette smokers age 45-54 where males had death rates about 50 percent
bigher than nonsmoking males, and females had deathrates about 100
percent ,higher than nonsmoking females. Under age 75, mortality
ratios for stroke ~increase as the number of cigarettes smoked increases.
No association has been shown for those aged 75 and over.
The new epidemiological evidence, then, indicates that cigarette
smoking may be more closely associated with cerebrovascular disease
than previously indicated in the population between the ages of 45 and
74 years. If cerebrovascular thrombosis (thrombotic brain infarction)
accounts for this association, it is possible that some of the considera-
tions of how cigarette smoking may produce coronary ththrombosis also
apply to the pathogenesis of cerebrovascular disease. Further research
is essential to understand the relationships which exist between ciga-
rette smoking and cerebrovascular disease
Additional epidemiological evidence from prospective mortality
studies provides confirmation that cigarette smoking is associated with
increttsed death rates from aortic aneurysm (nonsyphilitic), for both
men and women. In one study of male smokers an increase in death
rates was noted with increases in amount smoked.

HIGHLIGHTS OF CURRENT INFORMATION

1. Additional evidence not only confirms the fact that cigarette
smokers have increased death rates from coronary heart disease, but
also suggests how these deaths may be caused by cigarette smoking.
There is an incressing convergence of many types of evidence concern-
ing cigarette smoking and coronary heart disease which strongly sug-
gests that cigarette smoking can cause death from coronary heart
disease.

2. Cigarette smoking males have a higher coronary heart disease
death rate than nonsmoking males. `This death rate may, on the aver-
age, be 70 percent greater, and, in some, even 200 percent greater or


more in the presence of other known "risk factors" for coronary heart
disease. Female cigarette smokers also have higher coronary heart
disease death rates than do nonsmoking females, although not ss high
as that for males. In #general, the death rates from this disease increase
with amounts smoked. Cessation of cigarette smoking is followed by
a reduction in the risk of dying from coronary heart disease when
compared with the risk incurred by those who continue to smoke.
3. A greater frequency of advanced coronary arteri~lerosis is
noted in male cigarette smokers, especially in those who smoke heavily.
4. Additional evidence strengthens the association between cigarette
smoking and ~rebrovascular disesse, and suggests that some of the
pathogenetic considerations pertinent to coronary heart disease may
also apply to cerebrovascular disease.

28


Smoking and Chronic Bronchopulmonary
Diseases (Non-Neoplastic)

CONCLUSIONS OF THE SURCIEON GENERAL'S 1964 REPORT

1. Cigarette smoking is the most important of the causes of chronic
bronchitis in the United States, and increases the risk of dying from
chronic bronchitis.

2. A relationship exists between pulmonary emphysema and cig-
arette smoking but it has not been established that the relationship IS
causal. The smoking of cigarettes is associated with an increased risk
of dying from pulmonary emphysema.
3. For the bulk of the population of the United States, the impor-
tance of cigarette smoking as a cause of chronic bronchopulmonary
disease is much greater than that of atmospheric pollution or occupa-
tional exposures.

4. Cough, sputum production, or the two combined are consistently
more frequent among cigarette smokers lthan among nonsmokers.
5. Cigarette smvkmg IS associated with a reduction in ventilatory
function. Among males, cigarette smokers have a greater prevalence
of breathlessness than nonsmokers.
6. Cigarette smoking does not ap ear to cause asthma.
7. Although death certification Ii
                            s ows that cigarette smokers have
a moderately increased risk of death from influenza and pneumonia,
an association of cigarette smoking and infectious diseases is not other-
wise substantiated.

CURRENT INFORMATION, 1967

Additional evidence from the four major prospective studies indi-
cates that cigarette smokers have a markedly increased risk of dying
from chronic bronchitis and pulmonary emphysema. The range of
risk varies for cigarette smokers between three and 20 times the mor-
tality rates for nonsmokers, and depends in part on the total amount
smoked and the age group studied. Female cigarette smokers have
similarly increased mortality risks although somewhat lower than
those for males. Cessation of cigarette smoking is followed by a lower
mortality risk relative to those who continue to smoke. Generally, pipe


and cigar smokers are much less affected than cigarette smokers by
tha3ediseases.

Problems of nomenclature and diagnosis make satisfactory differ-
entiation of chronic bronchitis from pulmonary emphysema di&ult
when considering the epidemiologic data. Nevertheless autopsy studies
support the relationship between smoking and motiity. In addition,
recent information from morbidity studies indicates that smoking is
associated with symptoms of ch.i~Cc bronchopulmonary disease. Even
relatively young cigarette smokers show increased respiratory symp-
toms and decreased ventilatory funation. Cessativn of smoking is
usually followed by improvement of these characteristics. Although
some individuals may have an increased susceptibility to respiratory
disease, studies of twin-pairs in Sweden (& 6,6, I.,$)-in which one
twin is a smoker and the other is not-show that those who smoke have
a much greater frequency of respiratory symptoms and abnormalities
of ventilatory function than do their nonsmoking twins. This dem-
onstrates that cigarette smoking is of greater importance than hered-
itary and constitutional factors in the pathogenesis of chronic bron-
chopulmonary disease. Similarly, occupational exposures and air
pollution may also cause respiratory disease, but cigarette smoking is
of much greater importance.
Additional cliical and experimental laboratory evidence confirms
the fact that constituents in tobacco smoke are harmful to the bronchial
mucosa of the respiratory tract. Bronchial changes have been produced
in experimental animals exposed to cigarette smoke.

It is suspected that smoking has a direct toxic effect upon the alveo-
lar tissue of human lungs, in which case this effect might be important
in the pathogenesis of many though not all cases of human pulmonary
emphysema. Additional indirect evidence exists to substantiate this
suspected toxic effect, but additional research is needed to confbm or
deny the presence of the effect. However, the presently available evi-
dence (epidemiologic al, clinical, pathological, and experimental)
strongly suggests that cigarette smoking may well play an important
pathogenic role in many, although not necessarily all, cases of pul-
monary emphysema. The fact that other causes of pulmonary emphy-
sema exist does not detract from the validity of this inference.
Additional evidence strongly supports the conclusion in the Surgeon
General's 1964 Report that cigarette smoking is the most important of
the causes of chronic bronchitis in the United States, and increases
the risk of dying from chronic bronchitis.

30


HIGHLIGHTS OF CURRENT INFORMATION

1. New data confirm and to some extent strengthen the conclu-
siom of the Surgeon General's 1964 Report.
2. Cigarette smoking is the most important of the causes of chronic
non-neoplastic bronchopulmonary diseases in the United States. It
greatly increases the risk of dying not only from both chronic bron-
chitis but also from pulmonary emphysema.
3. C!essa$ion of smoking is followed by a reduction in mortality from
chronic bronchopulmonary disease relative to the mortality of those
who continue to smoke.
4. Even relatively young cigarette smokers frequently have demon-
strable respiratory symptoms and reduction in ventilatory function.

31


Smoking and Cancer

CONCLUSIONS OF TEE SUIWEON GENER~L'S 1964 Rnronr

1. Cigarette smoking is causally related to lung csncer in men; the
magnitude of the effect of cigarette smoking far outweighs all other
factors. The data for women, though less extensive, point in the same
direction.
2. The risk of developin
smoking and the number o P lung cancer increases with duration of
           cigarettes smoked per day, and is dimin-
ishedb discontinuin smoking.
3. Tie risk of deve(iop'
       Yc cancer of the lun
of pipe smokers, cigar smo ers, and pipe an cf for the combined group
                 cigar smokers is greater

than for nonsmokersl but much less than for cmette smokers.
The data are insufficmnt to warrant a conclusion for each group
individually.
Oral Cancer

1. The causal relationship of the smoking of pipes to the develop-
ment of cancer of the lip appears to be estabhshed.
2. Although there are suggestions of relationships between cancer
of other specific sites of the oral cavity and the several forms of tobacco
use, their causal implications cannot at present be stated.
Layngeid Cancer

Evaluation of the evidence leads to the judgment that c&ret-b
smoking is a significant factor in the causation of laryngeal cancer in
the male.
h'eophaged can&r

The evidence on the tobacco-esopha eal cancer relationship supports
the belief that an association exists. %I owvever, the data are not ade-
quate to decide whether the relationship is causal.
Cancer of Urinmy Bladder
Available data suggest an association between cigarette smoking
and urinary bladder cancer in the male but a? not s$clent to sup-
port judgment on the causal significance of this association.
Btmch ca;ncer

No relationship has been established between tobacco use and
stomach cancer.

33


CURRENT INFORMATION, 1967

Additional chemical, experimental, pathological, and epidemiolog-
ical evidence has been reported that substantiates the conclusions of
the Surgeon General's 1964 Report concerning the various sites of
cancer that were shown to be associated with or caused by smoking.

LUND CANCER

Deaths from lung cancer in the United States are continuing to rise
rapidly. Epidemiological evidence concerning cigarette smoking and
lung cancer has confirmed positive relationships with increasing num-
bers of cigarettes smoked, with increasing duration, and with deem-
ing age of initiation of the habit. Male cigarette smokers of less than
one pack a day have mortality ratios as high as 10 and smokers of more
than one pack a day have mortality ratios as high as 30.
There is a much smaller increase of the lung cancer death rates
associated with pipe and/or cigar smoking than with cigarette
smoking.

Additional evidence provides specific information on the increased
mortality ratios of female cigarette smokers. T~CW have significantly
elevated mortality ratios ranging as high as 5 for the groups with
greatest exposure. Lung cancer rates appear to be somewhat lower
for women who have never smoked regularly t.han for men who have
never smoked regularly. The mortality rates for women who smoke,
although significantly higher than for nonsmokers, are lower than
for men who smoke. How much of this is due to lower exposure to
cigarettes and how much to other factors cannot be determined from
the data available.

Ex-cigarette smokers are shown to have significantly lower death
rates compared with those who continue to smoke. As discussed under
the general topic of cessation earlier in this report, the finding of re-
duced lung cancer rates in the population of British physicians (8,9,
10) over a period of time in which t.he proportion of cigarette smokers
was dropping significantly can be interpreted as similar to a con-
trolled cessation experiment and provides critical confirmation of the
judgment that cigarette smoking is the major cause of lung cancer
and that sharp reductions can occur in the risk from lung cancer with
the cessation of smoking.

Additional information is available concerning the presence of
known or suspected carcinogens in tobacco smoke. It has been reported
that the %ar" and nicotine content of cigarette smoke* tends to reflect
the tumorigenicity of this smoke, and that a reduction of the "tar" and

* The pluase I6 YmJ and nicotine" is nsed! here as a general indicator oi total
parthlata matter fn cigar&t.e smoke.

34


nicotine content is accompanied by a reduction in the tumor&@&y.
Research is needed to identify and separate the tumor-initiating and
tumor-promoting agents in tobacco smoke and to elucidate their inter-
actions in the pathogenesis of cancer. Similarly, while additional data
are available concerning experimental carcinogen&s, it is not yet
certain that the typical characteristics of human squamous-cell lung
cancer, with invasion and metastasis, have been experimentally pro-
duced by t.obacco smoke in animals. It should be noted that this may
never be achieved not only because it may not be possible to duplicate
man's smoking action for anatomic and physiologic reasons but also
because of species' differences in cellular response.

There is evidence that certain other exposures, for example, occupa-
tional exposures to asbestos and uranium ore may interact with the
cigarette effect to produce an enhancement of the tumor-producing
effect. There is also information to indicate that the occurrence of
second primary lung cancers in smokers may be more frequent than
previously indicated.

ORAL CANCER

Substantial mortality ratios are found for cancers of the buccal
cavity and pharynx. Mortality ratios for cancer of the pharynx are
especially high. There is some evidence implicating alcohol and/or
dietary deficiencies in some of these sites. With the exception of the
pipe-lip cancer relations there are too few cases related to the indi-.
vidual parts of the buccal cavity to evaluate each independently, and
data are inadequate on the interaction of smoking with other factors.
Although all forms of smoking have high mortality ratios with these
sites, mortality ratios for those smoking cigarettes appear to be some-
what higher than for those smoking pipes and cigars, especially in
t.he case of cancer of the pharynx.

LARYNGEAL CANCER

Continued evidence from the prospective studies supports the exist-
ence of a high laryngeal cancer mortality ratio for pipe and cigar
smokers as well as for cigarette smokers. Data on the smoking habits
of patients treated for buccal cancer subsequent to their therapy sug-
gests that continuing to smoke after therapy may increase the likeli-
hood of an independent laryngeal cancer. The epidemiological evi-
dence supports the previous conclusion that cigarette smoking is a
significant factor in the causation of cancer of the larynx.

ESOPHAGEAL CANCER

Additional data from the prospective studies confirm the high
mortality ratio previously found for smokers of all forms of tobacco.

35


Aubpsy studies of smokers compared with nonsmokers speoiflcally
observingpathologicalchaqzsinesopbagealtissue havebeenreported
from both smokers and nonsmokers who died from causes other than
esophageal cancer. The findings were similar to the abnormalities
generally accepted as representing premalignant tissue changes of
the epithelium of the rv+ratory tract; that is, epithelial cells with
atypical nuclei were found far more frequently in cigarette smokers
than in nonsmokers. Tissue sections with basal cell hyperplasia were
also found more frequently in cigarette smokers and, as with the
atypical nuclei, these findings increased with amount of cigarette
smoking. Additional data to evaluate the relative importance of smok-
ing and alcohol, independently and jointly, would help clarify the
significance of these fIndings.

The Darn (19) and the Hammond (11) studies both show mortality
ratios over 2.0 for smokers of over 20 cigarettes a day, but the Doll-Hill
study (8,9), based on only 38 deaths, shows no apparent relation-
ship. Two retrospective studies have shown signi6cantly higher pro-
portions of smokers among patients than among controls. Small scale
metabolic studies suggest that cigarette smoking may block the normal
metabolism of tryptophan, which would lead to the accumulation of
carcinogenic metabolites in the urine. Further studies to verify this
finding and studies analyzing changes in the bladder tissue of smokers
as compared with nonsmokers would be helpful in arriving at a judg-
ment of the significance of the elevated death rates found in smokers
in the largest of the prospective studies.

Smsuxx AND PLLNCBEBTIC CANOEE

Epidemiological evidence does not show a sign&ant relationship
between smoking and stomach cancer. An association between ciga-
rette smoking and pancreatic cancer is implied, but the signi5cance
of this association is not clear at the present t.ime.

HIGHLIGHTS OF CURRENT INFOBMATION

LUNG CANCER

1. Additional epidemiological, pathological, and experimental data
not only confirm the conclusions of the Surgeon General's 1964 Report
regarding lung cancer in men but strengthen the causal relationship
of smoking to lung cancer in women.

36


9. Cessation of cigarette smoking sharply reduces the risk of dying
from lung cancer relative to the risk of those who continue.
3. Although additional experimental studies substantiate previous
experimental data, additional research is needed to specify the tumor-
initiating and tumor-promoting agents in tobacco smoke and to elu-
cidate the basic mechanisms of the pathogenesis of lung cancer.

LARYNGEAL CANCER

The conclusion of the Surgeon General's 1964 Report that cigarette
smoking is a significant factor in t,he causation of laryngeal cancer in
the male is supported by additional epidemiological evidence.

OTHER CANCERS

Additional evidence supports the conclusions of the Surgeon Gen-
CIY#S 1964 Report and indicates a strong association between various
forms of smoking and cancers of the buccal cavity, pharynx, and
esophagus. In the absence of further information concerning the in-
teraction of smoking with other factors known or suspected as causa-
tive agents, further conclusions cannot be made at this time, although
:L causative relationship seems likely.
Additional epidemiological, clinical, and experimental data
strengthen the association between cigarette smoking and cancer ,of
t.he urinary bladder, but the presently available data are insudcient
to infer that the relationship is ~causal.

37


Other Conditions and Areas of Research

CONCLUSIONS OFTHESUBOEON GENERAL'S 1964 REKSZT

Epidemiological studies indicate an association between cigarette
smoking and peptic ulcer which is greater for gastric than for duodenal

ulcer.
Tobacco AmbZyopia

Tobacco amblyo
lesion] has been re ated to pipe and
     P
gions. The association has not
or experimental studies.
Cirrhosis of tice Liver

Increased mortality of smokers from cirrhosis of the liver has been
shown in the prospective studies. The data are not sufficient to support
a direct or casual association.

Women who smoke cigarettes during pregnancy tend to have babies
of lower birth weight. Information is lacking on the mechanism
by which this decrease in birth wei
whether this decrease in birth weig 1 ht is produced. It is not kuown
                        t
logical fitness of &he newborn.     has any influence on the bio-

Psycho8ocid kbpects

The overwhelming evidence points to the conclusion that smoking-
its beginning, habituation, and occasional discontinuation-is to a
large extent psychologically and socially determined. This does not
rule out physiological factors, especially m respect to habituation, nor
the existence of predisposing constitutional or heredity factors.

CURRENT INFORMATION, 1967

By and large the contributions to knowledge in thii area of varied
considerations ,have been meager, although a number of investigations

27ll-3s4o-674

39


on one or another aspect of &he problem of smoking and varied health
consequences have been undertaken.

PIWTIC ULQm

The relationship between cigarette smoking and death rates from
peptic ulcer, especially gastric ulcer, is confirmed. In addition, mor-
bidity data suggest a similar relationship exists with the prevalence
of reported disease from this cause.

TOBACCO ~BLYOPIA

Tobacco amblyopia is now believed to be a manifestation of nutri-
tional amblyopia, which is aggravated by the inhalation of tobacco
smoke. Various vitamin B faotor deficiencies may be involved and
there is evidence to,suggest that chronic low vitamin B1* levels may
potentiate the toxic effects of cyanide in tobacco smoke.

CkRRHOSIS OF THE LIVER

Increased mortality of smokers from cirrhosis of the liver is found
in the prospective studies. This has generally been thought to be
largely secondary to an association between smoking and heavy con-
sumption of alcohol. Published data are inadequate to test this
interpretation.

MATERNAL SBIOEINO AND INFANT BIRTH WEIGHT

F'urther studies have confirmed the fact that women who smoke
during pregnancy `tend to have babies of lower birth weight, but
data are lacking to determine either the mechanism or the significance
of this findii.
            PSYCHOSOCIAL ASPECTS

There has been a sharp increase in the attention devoted to be-
havioral research since the Surgeon General's Report. A number of
new concepts have been developed and more sophisticated multivariate
approaches are being used. However, because of the recency of these
studies very little in the way of findings has been published on which
firm conclusions may be based.

40


Cited References

(1) BIT, E. W. It. A Canadian study of smolcing and health. Ottawa, De
  partment of National Health and Welfare, 1966.137 pp.
(2) BOOK, F. cf., hfooaa, (3. E., CLasK, P. C. ckrcinogenic aeHvity of dgarette
  smoke condensate. III. Biological activity of refined tar from several
  Q~S of cigarettes. Journal of the National Cancer Institute (Washing-
  ton) 34 (4) : 481-493, April 1965.

(3) BOBHAIV& N. 0.. HECETBB, H. H., BBIEBU)W, R. Report of a l&year foBowup
  study of the San Francisco longshoremen. Mortality from coronary heart
   disease and from all causes. Journal of Chronic Diseases (St. Louis) 16 :
   x251-x%8,1983.

(4) CEDE&WF, R. Urban factor and prevalence. of respiratory symptoms and
  "angina pectoris." A study of 9,188 twin pairs with the aid of mailed
  questionnaires. Archives of Environmental Health (Chicago) 13(6) :
   743-748, December 1968.

(5) CEDEBLOF, R., Fmumo, L., Jonsson, E., KAIJ, L. Morbidity among monzy-
  gotic twins. Archives of Environmental Health (Chicago) lO(2) : 348-3S0,
   February 1965.

(6) OEDEELOF, R., Finnuae, L., Joua~ou, E., EALT, L. Respiratory symptoms
   and %ngina pectoris" in twins with reference to smoldng habits. An
   epidemiological study with mailed questionnaire. Archives of Environ-.
   mental Health (Chicago) 13(6) : 728-737, December IQ@.
(7) DOLL, R. Cancer bronchique et tabac. Branches (Paris) M(6) : 313-324,
   Septembetitober 1966.

(8) DOLL, R., HILL, A. B. Mortality in relation to smoking: 10 years' observa-
   tions of British doctors. (Part 1.) British Medical Journal (London)
   l(53Q5) : 13QQ-1410, May 30.1964.

(9) DOLL, R., HI& A. B. Mortality in relation to smoking: 10 years' observa-
  tions of British doctors. (Concluded. ) British Medkal Journal (London)
   l(5306) : 148Ql48'7, June 6,19&L

(16) DOLL, R., HILL, A. B. Mortality of British doctors in relation to smoFsing:
   observations on coronary thrombosis. I*: Haenszel, W., editor. Epi-
   demiological Approaches to the Study of Cancer and Other Chronic
   Diseases. Bethesda, U.S. Public Health Service, National Cancer Insti-
   tute monograph No. 19, January 1966. pp. 2Q6-288.

(11) HAMxouo, E. C. Smoking in relation to the death rates of 1 million men
   and women. In: Haenssel, W., editor. Epidemiological Approaches to the
   Study of Cancer and Other Diseases. Bethesda, U.S. Public Health Service,
   National Cancer Institute monograph No. 19, January lQ38. Pp. 127-204.
(12) HOG. D., I~arm, F., WAI~~BOW, 5. Dosage patterns of cigarette smoking
   in American adults. American Journal of Public Health and the Nation's
   Health: [Inpress].
(16) mnu. H. A. The Dom study of smoking and mortality among U.S. veterans :
   report on 8?4 Years of observation. In: Haensel, W., editor. Epidemiologi-
   Cal Approaches to the Study of Cancer and Other Diseases. Bethesda,
  B.S. Pubhe Health Service, National Cancer Institute monograph No. 19,
   January 1968. Pp. l-125.

41


(Id). L~~~DLIAX, T. Smoking in relation to coronary heart disease and lnng funs.
   tion in twina A cotwin control study. Acta Medica ScandinaVCa (Stock-
   holm) 130 (eupplement 455) : 1-75.1353.
(IS) U.S. Puanro H~AL.TE Sx~vrc!x Smoking and health. Report of the Advisory
   Committee to the Surgeon General of the Public Health Service (Wash-
   ington). U.S. Department of Health, Education, and Welfare, Public
   Health Service publication No. ll03,1364.337 pp.
(16) U.S. PUBIZO HEALTH SE~BVICE. National Center for Health StatiStiC8. Cigar-
   ette emoking and health characteristics, United Stattee July I.364 to Juue
   1365. Washington, U.S. Department of Health, Education, and Welfare,
   Vital and Health Statistics series 10, No. 34, Public Health Service
   publication No. 1000, May 1967.64 pp.
(17) U.S. PDBLIO HEATH Suavxox, National Center for Health Statistics.
   Mortality from diseases associated with smoking : United States, 1950-34.
   Washington, U.S. Department of Health, Education, and Welfare, Vital
   and Health Statistics series 20, No. 4, Public Health Service publication
   No. 1000,Cctober 1036.45 pp.
(IS) U.S. Puma HEALTH Sxavxox. National Center for Health Statistics. Mor-
   tality-trends in the United States : 105MB. Washington, U.S. Department
   of Health, Education, and Welfare, Vital and Health Statistics series 20,
   No. 2, Public Health Service publication No. 1000, June 1936. 57 pp.
(19) U.S. PUBLIC HEALTH Sxuvrox. National Clearinghouse for Smoking and
   Health. Smoking and health bibliography, cumulation 1937 [in press].
   523 PP.
(90) WYXD~B, E. L., HOFFMIUPR, D. Experimental aspects of tobacco carcino-
   genesis. Diseases of the Chest. (Chicago) 44(4) : 337-344. October 1333.


PART II

  Technical Reports on the
   Relationship of Smoking
to Specific Disease Categories


CHAPTER 1

               CONTENTS

                                                  -P
Smoking and Coronary Heart Disease. .....................   47
Coronary Heart Disease Mortality. ...................   47
Coronary Heart Disease Morbidity. ...................    53
  Manifestations of Coronary Heart Disease ..............    58
  Cardiovascular Response to Smoking and/or Nicotine. ...    60
   Coronary Blood Flow in Normal Subjects. .........    60
   Coronary Blood Flow in Subjects With Coronary
      Heart Disease. ................................    61
    Carbon Monoxide Effect. ........................  62
    Studies on In V&o Thrombus Formation. .........    64
  Autopsy Studies .....................................    65
Smoking and Cerebrovascular Disease. ....................    66
Smoking and Aortic Aneurysm. ...........................    69
CitedReferences ........................................    69
Supplemental References. . . . . . . . . . . . . . . . . . , . . . . . . . . . . . . . .    76

Smoking and Cardiovascular Diseases

45


SMOKING AND CORONARY HEART DISEASE

CORONARY HEART DISEAEE MORTALITP l

The relative importance of the association between cigarette smoking
and coronary heart disease (CHD) as compared to the association of
smoking with other diseases was previously described in the introduc-
tion to chapter 11 of the Surgeon General's 1964 Report.
In the United States more persons die from coronary heart disease
than from any other single cause; and this most common form of fatal
cardiovascular disease accounts for a greater percentage of excess
deaths among cigarette smokers than do deaths from lung cancer. In
1964, there were 1,798,OOO deaths from all causes, of which almost
545,500 or 30.3 percent, were due to atherosclerotic heart disease,
including coronary heart disease. Table 1 gives the 1964 death rates for
WWNZ~ hart a?&ease per 100,000 persons by age and sex :

TABLE 1 .-196'4 death rates for coronaq heart disease per 100,000
          persons by age and sex

         All8g882544364445-6466-54    06-74     76BL     SS+
_-------___

Both Sexes_- 285.1  6.9 53.2 205.8 576.3 1,3849 2,957.7 6,882.g
Males------ 354.2 11.0 90.9 341.3 889.8 1,942.4 3,623.0 7,409.4
Females---- 218.5  3. 0 17.4 %. 3 286.4 926.5 2,464.0 6,559. 0

S008C~: N8ticUl8l Cant81 IOC HBalth StstistLa, (87).

These data illustrate &he dramatic increases in the risk of death
from coronary heart disease as age advances. For males the rates
among persons over the age of 45 appear to double from one decade
to the next; among females the increased risk of death with advancing
age is more dramatic-a threefold increase every 10 years. Of perhaps
greater importance are the relatively low death rates among females,
particularly below the age of 65, compared to males of comparable
age. The mortality differential between the sexes becomes less as age
advances ; under 45 years of age the coronary death rate among men
is five times as high as among women and in the 75-64 year age group
it is only about 1.5 times as high.

The Surgeon General's 1964 Report determined a median mortality
ratio (99) (pp. 109-110) for coronary heart disease of male current
cigarette smokers of 1.7. since this report, five large prospective

`All death ratea throughout this chapter are per 100,000 population, unless
0tJmvise indicated.                           47


studies of smoking and mortality have been updated on the basis of
longer periods of observation on each study subject. Current findings
are therefore more definitive and permit more detailed analysis of
the interrelationship of cigarette smoking to other significant variables
such as age, sex, and the nature of the smoking habit in terms of
amount and duration of smoking. Pertinent tidings are presented
below from the studies of veterans in *the United States (69) and
Canada (14) and the extensive data reported by Hammond (47)) Doll
and Hill (86, 8?6,97), and Borhani (17).

The relative excess mortality associated with cigarette smoking is
generally expressed in terms of a mortality ratio. This statistic is
defined as the ratio of the number of observed deaths among smokers,
to the expected deaths among smokers, if the age-specific mortality
rates observed among non-smokers had prevailed (69). The process
of computing the expected number of deaths among smokers takes
into account and adjusts for any differences in the age distribution
of the smokers and the nonsmokers under observation. Generally
smokers are defined as persons currently smoking cigarettes, and non-
smokers as lthose -who never smoked or who never smoked regularly.

Table 2 shows the mortality ratios for coronary heart disease deaths
among current cigarette smokers according to the amount smoked
daily in U.S. and Canadian male veterans.

TABLE 2.-Coronary hart disease morh%y ratios, age-adjwted among
    current cigarette smokers by amount smoked d&y

U.S. male veterans ______ -___- ______ -__-_
Canadian male veterans- _ _ _ _ - - _ _ _ _ _ _ _ _ _ _ _

CIgarettea smoked daily

uger   lO-3l   21-29 te   u)+

-----

1. 3   1. 7   1.8 ------ 20
1. 6   1.6 ______ 1.8 ______

Soumx: U.S. vatems stody (62) and Canadian pemstonen study (f4).

In both studies (&LX) *he mortalitiy ratios were similar and in-
creased with increasing i&ensity of cigarette smoking. Slightly higher
ratios are reported in the U.S. veterans study for current smokers of
cigarettes only.

The US. veterans study also permitted the comparison of age-
specific coronary heart disease mortality rates for ex-smokers and
current cigarette smokers (table 2A). From these data, it appears
that cessation of cigarette smoking is followed by a reduction in risk
of coronary heart disease mortality as compared to those who continue
to smoke cigarettes.


TABLE 2A.-Annuul o?eath rati per 100,000 f&n coronary he& dkeaae
by age, cigaretfe-smoking etatue and number of t$t&h sn&ed per
day, U.S. veterans study

T

T

46-M

m-64

66-74

--




--









-

Gmtmt
i!l%%

cnrrent
zzsE

Ex-
smokcm'

current
ffiZ22

~umbr smoked per day '

Ito9 ______-___-_-__    195
10to20 ________-_-__    297
21 to 39 ____-___-_-__    390
40+----------------    502

EX-
smokers '

125
133
57

._-_---.

594    432   1,374   1,105
a30    557  1,577   1,260
912    743   1,701   1,366
1,101    646   1,955   1,482

z E~~okerS who stopped for reasons other than doctor's Orders.
,$OUW.TE: U.S. veterans study (aa).

The Hammond study findings summarized in table 3 are based on
coronary heart disease deaths reported over a 4-year period among
approximately 1 million persons (441,000 men and 563,000 women).

TABLE 3 .-Coronary heart disease mortality ratios among current
    cigarette smokers only, by amount smoked oMy

-
I

Cigarattessmoked dally

Age and sex

Non-
smokers

Men:
  45to54--- ----_ -- ---___--    1.0
  55to64 _____________ - ____    1.0
  65toT4 ________ - _________    1.0
  75to84,--- ---_____-____- 1.0
Women:
  45to54 -__-_--___________ 1.0
  55to64,_-----_-----____- 1.0
  65to74 __________________ 1.0
  75to84 -_____-_______ -_--    1.0

' Exwcted deaths were leas than 10.
~~WRCIC: Hammond, E. C. (47.X

Under 10    lo-19

40+

.-

-

3.1    3.1
1.9    2. 0
1. 6     1.6
1. 4     1. 1

20
1. 6
1. 4

2. 7
20
  1. 9
____-__

  2. 4
  1. 5
  1. 3
  1. 2
0.9
  1. 3
  1. 1
- - - - - - .

   3. 4
   2. 1
(9
_ - - - _ _ - -


_-------
_-------
__-____-
- - - - - - - -

Tables 3 and 4 show that both men and women who smoke cigarettes
have relatively higher death rates from coronary heart disease than
nonsmokers, although men have higher rates than women. For each
sex and for each age group, the mortality ratios for coronary heart
disease generally increase with increased intensity of cigarette smok-
ing (table 3). The highest mortality ratios for both men and women
are observed in t.he 45-54 year age-group ; the coronary heart disease

49


death rates among heavy smokers in this age group are three times the
death rates for nonsmokers for both sexes. The mortality ratios for
both men and women decrease vith advancing age in each intensity
category. This trend may reflect the effects of selective survival of
smokers who have survived the elevated risks at younger ages of corm
onary heart disease and other diseases associated with cigareth
SIllOkiIlg.

Another explanation of the decrease in mortality ratios with aging
is that the effect of smoking, while substantial in increasing death
rates, cannot be expected to be proportionate to all other causes of
coronary heart disease as age advances. Considering the advanced de-
gree of atherosclerosis generally found among nonsmokers over age
65, the deleterious effect of smoking is more appropriately represented
by the excess in death rates among smokers. Table 4 below shows
the observed death rates from coronary heart disease among persons
studied by Hammond and classified by age, sex, and smoking status.
Although the mortality ratios decreased with age, differences in death
rates, which reflect the numbers of persons who die in each age group,
increase. This'could be interpreted to mean that, although relative to
other factors, the role of cigarette smoking tends to diminish with ad-
vancing age, the number of excess deaths per 100,000 smokers continues
to rise with advancing age.

TABLE 4.-Age-epeeiJic death raks from coronary heart disease per
    100,000 persims by age, 8ex, and smoking eta&e

Age and sex

Males:
  45to54------------------
  55to64---,--------------
  65to74--_---------------
  75tos34 _____-___-_-_____-
Females:
  45to54,__-_-----_-_____-
  55to64-----------------.
  65to74--- _______________
  75+--------------------.

1 Calcnleted from the data
Bowck: Hammond, E. C. [(/I). p. 145.1

Nonsmokers

--

422      150     272      2.8
996      542      454      1.8
2,025    1,400     625      1.5
3,871    3,132     739       1.2

66      33      33      2.0
275      163      112      1.7
941      653      288       1.4
2,349    1,973     376       1.2

The relative decrease in death rates from coronary heart disease
associated with the cessation of cigarette smoking is illustrated by
table 4A.

50


TABLE ~A.--COTO~M;GT~ heart disease (men). Age+tandardized o!eath
,'a&8 for t?X-Ci@Z?Vtte SmOkeT8 With hi&n-y Of C&re#e SmOkiTbg &y,
by former number of cigarettes smoked per day and years since last
cigarette smoking. Death rate8 for current cigarette smoker8 uith history
of cigarette smoking only ano? men who new smoked regukzriy are
8h0m fqr comparison. Men aged 60-69

                 Smoked l-19 cigarettes a day     Smoked !B+ dtpretted a day
Ep&gIretta SmOh~ (YearS
since last cigarette smokW z%   Nlllllber   Death  %z   NUCULXE  "Sh
                         ofdesths rate           of de8tba
--            -----        --        --

Under 1 year--- _-____    745    27 11,005   2,244     77  1 1,070
lt04years ____--__--  1,844     51    718 5,435     195   1,003
5togyeal-s __--------  1,770     48    725   5,803    152     732
lo+ years ___________ 4,209     84    498   8,142 205     679


    Total ex-
     smokers-----  8,569    210    635 21,624    630     813
Current cigarette
smokers- _ _ _ _- -_ _-_  22,808    781    947 56,886   1,895   1,029
Never smoked regu-
larly- _ _ _ ___ _-- _---  55,728   1,114    502 55,728   1,114     502


1 Four or mom but less than 10 deaths expected in 6ome of the component &yaar age groups.
SOURCE: Hammond, E. C. WI, p. 1481.
nolZ and EiJZ
In $5 prospective study by Doll and Hill (n) of mortality among
British physicians whose smoking habits had been previously recorded,
there were 1,369 deaths in the course of 10 years in which the underly-
ing cause was coronary heart disease ($7, table 1). The physician popu-
lation under observation totaled 320,185 person-years. The CHD
deaths were clas.si&d into three major subcategories: Group 1, com-
prising 35 CHD deaths in which an associated condition related to
smoking, e.g., lung cancer, was recorded on the death c&&ate; Group
i), comprising 721 CHD deaths in which no other significant contribu-
tory cause of death was recorded on the death certificate; and Group 3,
c&omprising 613 CHD deaths which were associated with some other
contributory cause, including conditions known to predispose t.o core-
llary heart disease, e.g., hypertension, diabetes, and obesity. The CHD
death rates for smokers and nonsmokers based only on Group 1 deaths,
while subject to large variatiofi, show the largest differentials (data not,
shown). Among smokers of 25 or more cigarettes daily, the age-ad-
justed CHD death rate was nearly eight times that in nonsmokers.
Based on Group 2 coronary heart disease deaths, presumably uncom-
l>licated by any other sign&ant disease, the mortality ratio of age-
:tdjusted death rates among continuing cigarette smokers to non-
smokers is found to be 1.6, and for heavy smokers to nonsmokers the


ratio is 2.0. However, as shown in table 5, the mortality differentials
between smokers and nonsmokers are much larger at the younger ages.

ThstE: FL-iUorta&y ralioe for di$krent typea of cormv h.mrt disease
          by mnoking h&$8
     I     Group 2 ' CHD  I      Oroup 8 CED

35 to44-------------
45to54-------------
55to64 _-___________
65to74-------------
75to84-------------
ssplua -----------___
                 -
Age adjusted-All agsa-

1.0    4.7    9.7
1.0     3.8    3.5
1.0 1.4 1.6
1.0     1.4    1.8
1.0     1.1    2.0
1.0    1.0 Q


1.0     1.6    2.0

__

1.0

-_

Cl    (`1
1.1     1.7
1.4     1.9
1.4   . .8
.a     .2
1.4   (9

1.1

.9

' Not calahbk no rata for mmamok~ because of so few deaths.
*Very few men in this category.
Souacr: Data in above table based on valups from Study of British l'by&Jans. Table 8 (27J.

The mortality ratios shown for Group 3 deaths, i.e., CHD deaths
accompanied by some other complicating disease, suggest that, for
all age groups combined, smokers do not have any special risk to
this type of coronary death. However, smokers below the age of 65
appear to be at a somewhat greater risk, while no consistent differen-
tials are observed among persons in the older age groups.

In summary, the study substantiates other mortality studies' find-
ings that CHD mortality ratios (current cigarette smokers vs. non-
smokers) increase with the number of cigarettes smoked daily, that
the ratios are highest in the age group 45-54, and that they decrease
as age advances. Moreover, smoking apparently is assooiated with
deaths from coronary heart disease among persons free of other
serious disease states.

In a prospective study of California longshoremen, Borhani (17)
reported on the mortality experience of more than 3,700 men observed
for 10 years. Table 6, derived from his data, provides some additional
insights on both the independent and the inter&ion effects of ciga-
rette smoking.

Men 45-64 years of age who were heavy smokers experienced higher
death rates from coronary heart disease than did nonsmokers independ-
ent of whether they were hypertensive or nonhypertensive.

52


TABLE 6.-Mortulitg ratio from corvnury h&W disea&?e amo?zg m&e
hypertensives and nonhypertensives by smoking history and age


    Age group           Blood ptpssarestatns 1          NOll- r
                                              -v
                                            smokus~    Emokus'
--

45 to ,rx,- _ ___ _ ____- Nonhypertenaive ______________     LO      2.2
          Hypertensive, _ _ _ _ ___ ---i ____ _     2.5      9. 6
55 to 64 ____________- Nonhypertensive -___-___------     LO      5.8
           Hypertensive, _ _ _______ __ _____     5.9      9. 4

1 Hyp&?l,S,V~ are de&& B(J tboSe b8m E$`StOlk blood m of MD mm. as. OX OV= M dbtCUc
,,,d presure of 9smm. H&T. or ov=. Nonh  &mslvfa hava ayatdlc blood praaau~ lem than 18 mm. m
cr dtastok? blood P-m @JE than 96 mm.
r~o,,smokaalnthiSpsrtiCUlSC8tUdyaFe 6fhed~SthOaen0tSmokh@8UYdW0tt=Orl~th1m~
        Y!
cigarettes per day. Smokem are those who smoke !ixl or mere pu day.
SOURCE: Borhsni, N. o., et 8l. (II).
,.n analysis was made by Schor (80) of 181 adult males who died
from coronary heart disease generally less than 2 years after receiving
;I periodic health examination. The results of this study and those of
Doll and Hill suggest that sudden death from previously undetected
coronary heart disease frequently occurs among cigarette smokers. If
tIlis is true, it may, in part, account for the small differentials in the
prevalence of coronary heart disease between smokers and nonsmokers
observed in some morbidity prevalence surveys. As will be described
in the following section, longitudinal, prospective morbidity studies
nlso show that smokers are more likely to die from sudden attacks of
coronary heart disease.
        CORONARY I&ART DISEASE MORBIDFIT*
In chapter 11 of the 1964 Surgeon General's Report, several prospec-
tive studies on the incidence of coronary heart disease (!34,31,78,88)
established that smokers were subject to higher rates than nonsmokers.
The relationship was reported to be more marked under 60 years of
age than among older persons and appeared to be associated with
myocardial infarction but not with angina pectoris. Since the 1964
report, recent findings from large-scale, on-going prospective studies
have been reported, providing additional insight on the interaction
between smoking and other important coronary heart disease risk fac-
tors. Current tidings are summarized in the following pages includ-
ing tables 7 to 13. Whenever possible, data are shown separately for
findings related to angina pectoris and those pertaining to myocardial
infarction, including sudden death attributed to coronary heart dis-
ease. Higgins (60) has drawn attention to the fact that "many factors
lnay influence or be affected by smoking habits, and obscure those
differences between smokers and nonsmokers which are directly re-
lated to the use of tobacco." In her review of the literature, Higgins
identified differences between smokers and nonsmokers in genetically
o 8lrso may include mortality data in this presentation.


determined qualities (M), in physique (77,98), in pemonality (87,
47, @, 65, 68, 69), and in social, cultural, religious, and economic
characteristics ($6, &,68,84).
Age

The elect of age on the incidence of coronary heart disease with
regard to cigarette smoking is shown in table `7 based on recent data
from the Framingham Study as yet unpublished.

TABLE 7.-ha+&imm raks and morbidity ratios for coronay be&
disease by age a& emoting status of men l%yew experience, Fm-
minghum, Maas.

AP

35to44 -_-___-_______________    1.4    4.1    2.7 T
                                      1.0 2.9
45to54 -_-__--_-________-____    4.6    11.1    0.5    1.0     2.4
55to64-----_-_---__-_____,__   16.2    25.4    9.2    1.0 1.6


SOURCE: U.8. Pnblk He&h Semke~, Fiamhgbam study (es).  (Updnted 1967)

When the incidence rate of coronary heart diseaseOamong male non-
smokers.between 35-44 yeers of age is compared with that among older
nonsmokers, the rate is seen to triple every 10 years. This marked
increase in incidence among nonsmokers reflects the effect of other
important risk factors and perhaps accounts for the decrease in mor-
bidity ratio as age advances. The independent effect of smoking on
the incidence of coronary heart disease is believed to be more appro-
priately represented by the excess morbidity rates, which increase
from 2.7 per 1,000 smokers in the age group 35-44 to 9.2 per 1,000
smokers 55-64 years of age.
&$b &!OOd ht?88WW?

Although the inhalation of cigarette smoke is frequently accom-
panied by acute transient elevations in blood pressure, habitual smok-
ers tend to have lower blood pressures than do nonsmokers (48). But,
given the presence of high blood pressure in an individual, smoking
acts as an additional risk factor for the development of coronary heart
disease (l7,$?8, m, 90,53,55,95, 96). Both the independent and the
combined effect of cigarette smoking is clearly shown in table 8 de-
rived from the experience of the Framingham and Albany studies
(W*

54


TABLE 8.-Ageadjualed morbidity ratios for coronary heart disease
among smokers and nonsmokers according to level of systolic blood
pressure

          Systolic blood p-       Noos"p;z of  "2ZJC
                                     -        ---

Under 130mm.Hg___--__------___-___--__--_--       1.0        2. 1
130 mm. Hg and over- _ _ _______________________       1.8        3.8

SOURCE: l&year Framingham and &yesr Albany experienci (3%
Eigh sem choze-stt?roz

It is not now conclusively known if cigarette smoking by itself can
cause increases in serum cholesterol. Dietary influences as well as en-
dogenous production and elimination of cholesterol must be evaluated
in greater detail with simultaneous analysis of the roles of other
risk factors, including smoking. One study of a small population of
twins in Sweden, as reported by Lundman (67)) suggests that smoking
monozygotic twins tend to have lower cholesterol levels than their
nonsmoking control twins, although the differences are not statistically
significant. Other studies suggest that smokers generally have higher
serum cholesterol than nonsmokers (13, 37, 88). However, given the
presence of high serum cholesterol, smoking increases the risk of cor-
onary heart disease (96,96').

The independent any synergistic effect of cigarette smoking is dem-
onstrated by the data in table 9 derived from the combined experience
of the Framingham and Albany studies (30).

TABLE O.-Age-adjusted morbtiity ratios for coronary heart disease
among smokers and nonsmokers according to level of serum cholesterol

Serum cholest~ol level

Low'-_-___--____________________________-----       1. 0        1. 8
Highs-___________-___________________------       2. 0        4.5

1 "Low" is below m&an. %igh" is above median value of sermn chloeaterol.
SOURCE: l&year Fmmiughcm and &year Albany esperfence (Jo).
Puzmonar/y Fzunction

The acute effects of cigarette smoking upon pulmonary function are
expressed mainly through increase in airway resistance. The dif-
ferences in pulmonary function between smokers and nonsmokers ap-
pear to be greater than can be accounted for by acute effects from a
recently smoked cigaretta (50,91). The relationship of coronary heart
disease to lowered pulmonary function as reflected by low vital capacity
and cigarette smoking is observed in the data published by the Na-

z7&SQ4 o-67--5                            55


UUU~~ msmutes oi Health based on the 12-year experience in Framing-
ham (96). Morbidity ratios derived from this publication are shown in
table 10.

TABLE lO.-Age+dju&ed mo&idiiy ratios fw coronary he& disease
among smokers and nonsmokers according to IePel of erital cupa&y

wal capacity

Under 3 liters _-_---_ - ___ ___ _ ______ _ _________ ___       1.0
      I I
3 liters or more ---------------------------------      1.7

1.7
2.4

Sonaclr: The FraxnIngham heart study. (6W).

Here again, the independent and combined effects of cigarette smok-
ing are observed.
Physical znaotivity

A physically inactive or sedentary individusl seems to run a higher
risk of developing coronary heart disesse (89, .&I, 0,76). Spain (88)
reported that, in his prospective study of 3,000 men "* * * the rela-
tionship of occupational physical activity to smoking habits revealed
that one of six sedentary workers were heavy smokers and one of five
strenuous workers were heavy smokers." Weinblatt, in reporting the
experience of the Health Insurance Plan of Greater New York (100)
also found that a higher proportion (41.9 versus 36.0 percent) of cig-
arette smokers were classified in the "most active" physical activity
category.

The independent and the combined effects between cigarette smok-
ing and physical activity are shown in table 11. The morbidity ratios
for myocardial infarctions are derived from published data.

TABLE ll.-Age-cs&justed morbidity ratios for myocardti infarctions
among smokers ano! nowmokers according to phgsi.eal act&i@ &we1

Physical actitity

Most active------------_------_---_____-____-__       1. 0
      I I
Lenstactive---------_-_-----------~-----------       24

2. 6
3. 4

SOUBCE: Weinblatt, E. (fOrI).
Socioenvironmenta.2 Stress

Since 1955, research on socioenvironmental stress in relation to cor-
onary heart disease has increased greatly (#, 99). Among the factors
studied that indicate a strong association with coronary heart disease
incidence and prevalence is sociocultural mobility, that is, moving
from one social setting to another. The interaction of this factor and

56


cigarette smoking has been reported by Syme (90,91) in both an ur-
ban and rural setting. Apparently in both areas cigarette smokers
\vere more culturally mobile than nonsmokers. The independent effect
of cigarette smoking on the incidence of coronary heart disease is
shown in the morbidity ratios in table 12 derived from the North
Dakota study (91).

TABLE 12.-Age-adjusted morbidity ratios for coronary heart d&ease
among smokers and nonsmokers according to sociocu&uraJ mobility
status

socioouItumI status

Ne;wwT$ed   Current and
     fonn~ok~grette

stable __________________ - ____ - _______________ -       1. 0
     1 1
Ijighly mobile--- __ _- ____ -__ ___ ___ _ __ _ ___ _ ___ ___       2. 3

1. 5
3. 2

SOURCE: North Dakota study. (81)
Personality Type

Various investigators have long `suspected a possible pathogenetic
role of the central nervous system in coronary heart disease (35). In
a series of reports, Rosenman (82,8@ and Jenkins (51) have described
a personality pattern or overt emotional complex which, while asso-
ciated wit.h other known risk factors, appears to predict coronary heart
disease more effectively than do other risk factors. This emotional com-
plex, `&which they have termed Behavior Pattern Type A, is composed
of an enhanced competitiveness, drive, aggressiveness and hostility,
nud an excessive sense of time urgency." Recent unpublished data based
upon prospective observation of more than 3,000 men for a 4+`&-year
period (51) discloses that smokers have a higher percentage (54 versus
4'7 percent) of type A persons among them. Moreover, the incidence of
coronary heart disease is shown to be related independently to both
smoking status and personality type. Morbidity ratios, derived from
the incidence data, are shown in table 13 which clearly demonstrates
the independent effects of cigarette smoking and its interaction with
personality characteristics.

TABLE 13.-Morbidity ratios of cigarette smokers as compared to non.-
         smokers by personality type

SOUBCE: Unpublished data from We&em Collaborative Group Study, San kandseo, C&if. (eb).


Mdtiple-R&k Factor8

The method of analysis traditionally employed by epidemiologists,
that of the comparison of rates for. multiple cross-classifications of
the data, generally requires a large study population at relatively high
incidence of significant events. Since coronary heart disease incidence
rates are low and study populations are necessarily small because of
practical and practicable limitations, definitive analysis of the inde-
pendence and interaction between risk factors have generally been re-
stricted to two factors at a time. Truett (96) applied a multiple logistic
function proposed by Cornfield to investigate the independent effect
on the incidence of coronary heart disease of seven risk factors: Age,
serum cholesterol, systolic blood pressure, relative weight, hemoglobin,
cigarettes per day, and ECG abnormalities. The method was used in the
analysis of data compiled in the Framingham study during a 12-year
period. A discriminant function coefficient was computed for each risk
factor. These-coefficients represent the relative importance of each fac-
tor with respect. to the other six factors in the development of coronary
heart disease. While theoretical considerations underlying the logistic
risk function are not fully satisfied by the actual data, the approxima-
tion given by the function to observed rates is very good.
Consequently, Truett and Cornfield believe that the present compu-
tations permit the conclusion that "the most important risk factors,
aside from age itself, are cholesterol, cigarette smoking, ECG abnor-
mality, and blood pressure" (96).

MIANIFE~TATION OF CORONARY HIURT DIEIEASE

Coronary heart disease is essentially comprised of three major mani-
festations or subcategories :
    1. Fatal myocardial infarctions, including sudden deaths attrib-
uted to coronary heart disease ;
  2. Nonfatal myocardial infarction; and
  3. Angina pectoris.

Generally, investigators in their analysis of the relationship of risk
factors to the incidence of coronary heart disease have not subdivided
the observed coronary events into the three major subcategories pri-
marily because the paucity of events in each category did not permit
definitive conclusions on any differences observed. However, the pool-
ing of data from some of the larger prospective studies holds promise
of a more complete analysis of the independent and synergistic effects
of each risk factor on each of the subcategories of coronary disease.
Findings from these analyses might provide some insights into the
underlying pathophysiological mechanisms t.hrough which a risk factor
operates. The pooled data from the Albany and Framingham studies
a.nd data from the HIP study include the observed associations of

58


cigarette smoking with each of the three major manifestations. Mor-
bidity ratios have been derived from these studies and are presented
in table 14.

TABLE 14.-Agemfjusted nwrbidity mtios for subcategories of coronary
     heart disease among smokers and nonsmokers

                        Framingham-Albany   Ewaltll fneurance plan
        Disease category             Non-  "&Tg    NOU-
                             smokem of          smokea of
                         cIgarettea         clgncettes  "m%
-        --- ~-- --- ~_
Fatal myocardid infarction _________      1. 0    2. 4      1. 0     2. 1
Non-f&d myocardial infarction- _ _ _ _     1. 0    2. 3      1. 0     1. 8
Angina pcctorie __________ ___ ___ _ ___     1. 0     1. 1      1. 0     1. 7

Socmcr: Second Report of the Comblned Erperlence from Albany and Framingbarn Studies (JO). VII-
&dished Data from Health Innuance Plan Study (loo).

The association of cigarette smoking to angina pectoris is not a con-
sistent one. A clear-cut association was found in the Health Insurance
Plan Study (ratio of 1.7) ; a similar association is also found in un-
published data from Framingham considered separately. However, no
association between cigarette smoking and the incidence of angina
pectoris was found in the Albany experience. Cederlof (19)) in his
analysis of prevalence data on angina pectoris obtained by question-
naire, found no statistically significant difference in prevalence rates
between 453 monozygotic twin pairs with dissimilar smoking habits.
In a larger study of about 9,000 persons from the twin register where
genetic factors were uncontrolled, Cederlof (19, m) did find a sig-
nificantly higher prevalence of angina pectoris among smokers than
nonsmokers, particularly in men (ratio of 1.6) (fl) .

Friedman (&!) and Epstein (96) have clearly described the in-
herent biases in prevalence studies which may lead to findings of risk
gradients that are different from those obtained in prospective inci-
dence studies. One of these limitations is that fatal cases are under-
represented in a prevalence survey. Thus, since it appears that cigar-
ette smoking is more closely related to the incidence of fatal myocar-
dial infarctions than to other forms of coronary heart disease, it is ex-
pected that morbidity ratios derived from prevalence surveys would be
lower than those computed from incidence data. With these restrictions
in mind, Russek (83) in a survey of 12,000 men in 14 occupational
groups found that the morbidity ratio of coronary heart disease preva-
lence among cigarette smokers was as high as 1.8. In contrast, in a study
of 77 identical and 89 fraternal twins in Sweden, comparing smokers
with their respective no