TABLE Z.-Coronary heart disease morta&

                 (Actual number of deaths

                       [SM = Smokers

Author,
Year,
countrY, NutymFo;nd     Data
reference  oooulation    collection

Hammond  187,783     Question-      3%    5,297  NS .l.OO  (709)
and      white males   naire and        All smokers .1.`70 (3361) 2(p<o'oo1)
Horn,     in 9 states    follow-up              <lO .1.29  (192)
1958,      50-69 years   of death                lo-20 .1.89 (864)
U.S.A.    of Bge.      certificate.               W-40 .2.20  (604)
(77. 78).                               >40 .2.41  (118)

Follow- Number
(Yeuaprs,   of
     deaths

Cigarettes/day

Doyle     2,282 males.   Detailed      10       93  NS .l.OO   (20)
et al.,     FLW"-      medical               All smoken .2.40   (73)
1964.     ingham. examina-              <20 . . .2.00   (17)
U.S.A.     30-62 years   tio" and                20 .1.70   (20)
(54).     of age.     follow-up.     8         >20 .3.50   (36)
       1,913 males.
         Albany,
         39-55 years
         of age.

Doll and    Approxi-    Question-     10     1.376  NS  _. .l.OO
Hill.      "lately      "sire and              All smokers .1.35
1964,      41.000      follow-up                1-14 .1.29
Great     male British  of death                 15-24 ,127
Britain    physicians.   certificate.              >25 .1.43
(50).

Strobe1    3,749 male   Question-      s      162  NS  . . .l.OO
and Gsell   Swiss phy-   naire and
1965      sicians.     follow-UP               l-20  .1.48
Switzer-            of death               >20 . .1.16
land               certificate.
(180).

Best,      Approxi-    Question-      6     2.000  NS  _. .l.OO
1966      mately     naire and              All smokers .1.60 (1380)
Canada    78.000      follow-up           -  <lO . .1.55  (337)
(24).     male Cana-   of death               lo-20 .1.58  (766)
         dian       certificate.              >20 .1.78  (277)
         veterans.

Kahn
1966
U.S.A.
(98).

U.S. male
veterans
2,265,674
person
y-2al.S.

Hirayama. 265,118
1967.      Japanese
Japan     adults over
(84).     age 40.

Question-
naire and
follow-up
of death
certificate.

        -
Trained in-
terviewers
and follow-
up of death
certificate.

s/r,   10,890  NS  .l.OO (2997)
         Allsmokers .1.74 (4150)
         l-9  1.39  (439)
         10-20  .I.78 (2102)
         21-39  . 1.84 (1292)
         >39 2.00  (266)

1      91   NS .l.OO  (17)
         l-24 __ ., .1.13  (69)
         >25  .l.OO   (5)

Kannel    5,127 males   Medical ex-    12       52  NS _. .l.OO (27)
et al..     and females   amination             SM>20 ,220 125) 3 (P<O.O5)

1968,      age 30-5s.    and
U.S.A.             follow-up.
(94).

1 Unless otherwise specified, disparities between the total number of deaths
and the sum of the individual smoking categories are due to the exclusion
of either occasional, miscellaneous, mixed, or ex-smokers.

26


ratios related to smoking-prospective studies

shown in parentheses ) 1

NS = Nonsmokers]

Cigars, pipes

Age variation               Commenta

Cigars               so-54    55-59    60-64    65-89
NS. .l.OO       NS . 1.00  (90)  1.00 (142)  1.00 (204) 1.00 (273)
SM. .1.28 (420)    Allsmokers  .I.93 (765)  1.85 (962)  1.66 (921)  1.41 (713)
Pipes        :I0 . ..1.38  (35)  1.38  (50)  1.17  (49)  1.27  (58)
NS. .l.OO       lo-20 .2.00 (213) 2.04 (258)  1.91 (235)  1.68 (158)
SM. .1.03 (312)    >20 . ..2.51 (203) 2.47 (199)  1.92 (129)  1.56  (73)

Data apply
only to males
aged 40-4s
and free
of CHD at
entry. NS
include pipe.
cigar and
ex-smokers.

       35-44    45-64    65-84
NS     .l.OO     1.00     1.00
1-14      .3.73     1.40     1.71
16-24      .4.45     1.73     1.27
225      .1.36     1.92     1.68

NS. .l.OO
SM. .1.45

Cigars               30-49    50-69    70 and over
NS. .I.OO       NS  .l.OO     1.00     1.00
SM. .0.98  (16)   <lO  ..__. . ..0.97  (18) 1.56 (220)  1.71 (99)
Pipes        lo-20   .1.45 (115)  1.67 (567)  1.29 (94)
NS. .l.oo       >20  ,. _. __ .1.85  (65)  1.76 (184)  1.73 (28)
SM. .0.96  (95)

cigar.4
NS. .l.oo
34. .1.04 (628)
Pipes
NS. .l.oo
SM. .1.08 (386)

Prefimin-
arY report.

' "P" values specified only for those provided by authors.

27


TABLE 2.-Coronary heart disease mortality ratios

(Actual number of deaths
    [SM = Smokers

Author,
Year.    Number and
country,    b-P.2 of
reference   population

       Follow- Number
Data           of           Cigarettes/day
collection  (Y%)  deaths

Hammond   358,534
and      male!3
Gartinkel,   445,875
1969,      females
U.S.A.     age 40-7s
(76).     at entry.

Question-
naire and
follow-up
of death
certificate.

                              -
6    14.819          Make Females
         NS  .l.OO   1.00
         1-9  .1.27   0.84
         lo-19  .1.60   1.22
         20-30  .1.73   1.52
         >40  .1.77   0.61

Paffenbar-  50,000 male   Baseline     17-51    1,146   NS  . . . . .l.OO
ger and    former     interview        matched  3M  .1.50 (385) (p<o.ol)
Wing     students.    and ~XBIII-         with
1969               ination and        2,292
U.S.A.             follow-up        controls
(146)              by death
                  certificate.

Paffenbar-  3,263 male   Initial multi- 16     201   NSand<ZO 1.00 (137)
ger et al.,   longshore-   phssie          SM >20 .2.08 (154) (p<o'ol'
1970,     men 35-64    screening
U.S.A.     years of     and follow-
(144).     age.       up of death
                  certificate.

Taylor     2,571 male    Interviews      5      46   NS  .l.OO   (4)
et al..     railroad     and regulxr             :20 .1.97   (20)
1970,      employees    follow-up               >20 .3.60   (22)
U.S.A.     40-59 years exam-
(183).    of age at    ination.
         entry.

Weir and   68,153 Csli-   Question-     5-8     1,718  NS .l.OO
Dunn.     fornia male   mire and              All smokers .1.60
1970,      workers     follow-up              210 .1.39
U.S.A.     35-64 years   of death               520  1.67
(205).     of age at    certificate,              >30 ,, .I.74
         entry.

Pooling    7,427 white   Medical ex-    10      239  NS .l.OO  (27)
Project,    nK+les      amination              <lO . ..1.66  (34)
American   30-59 years   and                   20 .l.lO  (86)
Heart     of age at    follow-up.              >20 ._.. .3.00 (68)
Associa-    entry.
GO".
1970,
U.S.A.
(88).

1 Unless otherwise specified, disparities between the total number of deaths
and the sum of the individual smoking categories are due to the exclusion
of either occasional. miscellaneous, mixed. or a-smokers.

28


wleted to snloliing-l)rospective stztdies (cont.)

shown in parentheses) '

NS = Nonsmokers]

Cigars, pipes                   Age variation                Comments

        41/-&Y
NS  .1.00
1-u .l.fiO
IO-19 ,.  .2.69
?ll-30  3.76
>40 5.51

NS   1.00
l-9 .1.31
10-19 .2.08
20-30 .3.62
>40 .t3.31

   Ml&d
51,-59    60-CY
1.00     1.00
1.59     1.48
2.13     1.X2
2.40     1.91
2.79     1.79
  FtVTll7lCS
1.00     1.00
1.15     1.04
2.37     1.79
2.68     2.08
3.73     t2.02

70-79
1.00
1.14
1.41
1.49
1.47

tBased on
5-S deaths.

1.00
0.76
0.9R
1.27

        JO-44    45-5:    55-69
NS .l.OO     1.00     1.00
        (P<O.Ol )

SM 1.80 (88) 1.60 (163) 1.20 (134)

Data apply
only to
those free
of CHD
at entrY.

       35-44
NS  ....... .l.OO
ZlO  ....... .4.22
k20  ....... .6.14
530  ....... .8.57
>40  ....... .7.93
All  ........ .6.24

45-54    55-64    65-69
1.00     1.00     1.00
2.05     1.41     1.17
3.17     1.64     1.26
3.33     1.66     1.36
3.15     1.42     1.42
2.95     1.56     1.24

NS includes
pipes and
cigars.
SM includes
ex-smokem

1.00 (27)
1.20 (24)

29


TABLE 3.-Sztdden death frow coronary
        (Mortality ratios--actual number

Author
year,
country,
reference

Numbw and
type of
population

Data       Follow-up
collection       years

   -

Number
of
deaths

Pooling
Project,
American Heart
Association,
1970. U.S.A.
(b-8).

7,427 white
males 30-5s
years of age
at entry.

Medical
examination
and
follow-up.

10        145

TABLE 4.-Coronary heart disease

             (Risk ratios--actual number of CHD

              [SM = Smokers   NS = Nonsmokers


PRCISPECTIVE STUDIES

Author,
Year.    Number and     Data     Follow-   Number of
country.     type of      collection     UP     incidents
reference   population              years

Cigarettes/day

Detailed       10   243muo-    NS .l.OO (52)

medical
examina-
tion and
follow-u*.

cardial    All smokers ._ .2.36(191)
infarc-     <20  _. _. .1.98 (44)
tions and   20 . . . . . . . . . . ...2.05 (64)
CHD      >20  3.04 (83)
deaths.

Doyle     2.282 males
et al.,    Framingham,
1964,     3C-62years
U.S.A.    of age.
(5.4).   1,913 males
        Albany,
        39-55years
        of sge.

stam1er   1,329 CHD-
et al.,    free male
1966,     employees of
U.S.A.    Peoples Gas
(177).    CompanY
        4b-59 years
        of age.

Epstein,   6,565 male
1967,     and female
U.S.A.    residents
(61).    of Tecumseh.
        Mich.

Interview       4   46 CHD     NS ._ ._ .l.oo (27
and exarnin-
ation with          <lO cigarettes. 2,S2 (6)
                       < 5 cigars.... I
clinic                     < 5 pipes.....
follow-up.                  10-19 cigarettes.3.67 (8)

>20 cigarettes. 3,83 (2S)
> 5 cigars. ._ I
> 5 pipes.....

-

Initial
medical
examinit-
tion and
repeat
follow-up
examinlr-
tions.

4    96 male.                M&8
     92 fern&              40-59
     CHD in-    NS .__... . ..l.OO  (1)
     &ding    EX ._. ._..... 6.53 (10)
     deaths,    Cigarettes  .5.!20 (36)
     angina, and            Females
     myocardial  NS _. .l.OO (21)
     infarctions. EX .0.89  (3)
             Cigarettes  .1.02 (14)

`Unless otherwise specified. disparities between the total number of mani-
festations and the sum of the individual smoking categories are due to the
exclusion of either occasional, miscellaneous. mixed, or ex-smokers.

30


/,! r11.f rlisease related to smoking

,,f deaths shown in parentheses)

Cigarettes/day         Cigars, pipes          Comment

St.v.cr smoked  ........... 1.00 (15)    1.00 (15)   See table 1 for description of
10  .................. .1.90 (23)    1.36 (13)     Pooling Project.
20  ................... .1.90 (50)
>2"   ................ ..3.3 6 (44)

,uorbidity as related to smoking

manifestations shown in parentheses) 1

EX = Exsmokersl

PROSPECTIVE STUDIES-Continued

Pipes, cigars          Age variation           CO"l"X"ts

Data include
CHD deaths,
only on males
40-49 years of
age and free of
CHD on entry.
NS includes
pipes, cigars.
and ex-smokers.

NS includes
a-smokers.
Includez all
CHD.

Males-Continued
  60 and over
   1.00 (7)     SM
   1.27(11)
  1.96 (23)     SM
FCmales-Continued
  1.00(47)
   1.31 (5)
   0.42 (2)

M&8
  40-59
.1.80(Z)
60 and Gwer
. ...0.86(6)

Reexamination
of patients
was spread
over l$$-byear
period, but
data are re-
ported in
terms of
4-year inci-
dence rates.
Actual number
of CHD inei-
dents derived
from data on
incidence and
total in smok-
ing class.

31


TABLE 4.-Coronary heart disease
   (Risk ratios--actual number of CHD
  [SM I Smokers   NS = Nonsmokers

PROljPECTIVE STUDIES

Author,
year.
country,

Number and
type of

reference   population

Jenkins,   3,182 males
et al.,     39-59 years
1968,     of age at
U.S.A.    entry.
(90).

Data
collectioll

Initial
medical
examina..
tion and
follow-up
by repeat
examina-
tions.

Follow-
UP
Years

4:;

Number of
incidents

Cigarettes/day

104 myo-     NS . . . . . . . . . . ..I.00 (21)

eardial     EX  ........... .2.47 (15)
infarctions. Current  ...... .2.78 (68)
        O-15:day  ..... .t1.39 (45)
        >I6 .......... ..3.0 6 (59)

K@.ollel,   5,127 males
et al.,     and females
1968.     30-59 YQB1`S
U.S.A.    of age.
(9.5).

Medical       12
examina,.ion
and follow-
UP.

Shapiro   110,000 male    Baseline med-    3
et al.,     and female     ical inter-
1969.     eor0llee5      view and
U.S.A.    of Health      examination
(172).    Insurance     and regular
        Plan of       follow-up.
        Greater
        New York
        (HIP)
        35-64 y-ears
       of age.

228 myo-       Myocardial Infarction
cardial                M&8
infarc-    NS ._ .l.OO (21)
tions.     All SM 1.51(153)
380CHD.   Heavy SM .I.85 (59)
           Risk of CHD (mwrall)
                    M&8

NS ._ .l.OO (61)
l-10 .1.34 (25)
11-20 .1.80 (90)
>20  .2.41 (76)

                       -
Total                 Moles
unspeci-    NS  .l.OO
fied.      All current .2.14
          cigarettes ( p<O.Ol)
         <20 .1.50{
         >20 . . . . . . . . ...2.33/
         >40  . . . . ...6.36

Keys
1970
Yugo-
slavia
Finland
Italy
Nether-
lands
GrWCe
(Ill).

9,186 males     Interviewr.     5      65 deaths.   NS, EX
in 5 coun-      and rcgu-          80 lnYocar-    (SM <20) .1.00(305)
tries 40-59     lar follow-           dial in-   All current
gears of       up examina-          farctions.   020)  .1.31(103)
age at entry.    tion by           128 angina
            local              pectoris.
           physicians.         155 other

t428 total.

`Unless otherwise specified, disparities between the total number of mani-
festations and the sum of the individual smoking categories are due to the
exclusion of either occasional, miscellaneous, mixed. or es-smokers.

32


morbidity as related to smoking (cont.)
manifestations shown in parentheses)'
EX = Ex-smokersl

PROSPECTIVE STUDIES-Continued

Pipes, cigars

Age variation           Comments

~P<O.OOl)

(P<O.OOl)
(comparing
CA5 and 16+)

      99-49    so-59
NS. .l.OO (4)  1.00 (6)
Current 4X3(35) 2.26(33)

tIneludes non-
smokers and
ex-smokers.
NS includes
former pipe
and cigar
smokers.

Myocardial infarction-Continued
FeWlde8
1.00(31)
1.71(23)

Risk of CHD (overall)-Continued
FWl&*
1.00(89)
0.86(U)
1.29(x3)
0.93 (3)

Females        Males onlg
  1.00         NS .l.OO
  2.00         SM .1.82
(Y>O.Ol)          (P<O.Ol)

1.77

5.92

   Ml&8         F&?WW&3    Total myo-
ss-44 1.541 55-64  35-44  45-54 55-64  cardial in-
1.00  1.00  1.00    1.00   1.00  1.00   far&ion in-
2.47  3.06  1.69    2.25   2.67  1.80   eludes those
0.52  2.15  1.32~
3.04  3.29  1.81j   1.25   2.31  1.66   dead within
                         48 hours.
10.09  7.69  5.30   20.25  11.79  4.07
                        NS include
                         a-smokers.

Includes all
CHD incidence
including EKG
diagnoses.
Covers all
countries in-
vestigated
except U.S.A.
t Difference
between total
CHD and the
sum of smoking
group8 is due
to difference
in figures
presented by
authors.

33


TABLE 4.-Coronary heart disease

              (Risk ratios--actual "umber of CHD
             [SM = Smokers   NS = Nonsmokers

PROSPECTIVE STUDIES

Author,
Yea=,
country.
reference

Taylor.
et al.
1970
U.S.A.
(183).

N"t;m yo;"d
population

2.571 male
railroad
employees
40-59
years of
age at
entry.

Data     Follow-
collection     UP
        Y.X3*S

Interviews     5
and regu-
lar follow-
up examina-
tion.

Number of
incidents

Cigarettes/day

46 deaths.   NS and EX .l.OO (62)
33 myocar-  All current .1.77(150)
dial-in-
farctions.

78 angina
pectoris.
55 other
  CHD.

212 total.

Dayton   422 ma1eU.S.    Interviews    "p to 8 27 sudden    <lO  .l.OO (25)
et al.,    veterans par-   and routine         deaths.    IO-20 . . . . . . . ...1.04 (22)
1970,    tieipating as    follow-up         44 definite   >20 . . . . . . . . ...1.17 (13)
U.S.A.    controls in s    examina-          myoeardial
(4% 49).  clinical trial of   tions.            infarctions.
       a diet high in
        unsatu-
        rated fat.

DU""    13,148 male     Data only    up to 14 Total un-
et al..    patients in     on new           specified.
1970     periodic health   incidents
U.S.A.    examination    extracted
(55).    clinics.       from
                   clinic
                   records.

Pooling   7.427 white     Medical       10      538
Project,    males 30-59     examinai ion        Includes     Never smoked .l.OO (53)
American   years of       and follow-         fatal and   <lO  .1.65 (72)
Heart     age at entry.    UP.              nonfatal     20  . . . . . . . . . ..2.08(205)
Association                           myoeardial  >20 ,328 (154)
1910.                                infarction
U.S.A.                               and sudden
(88).                               death.

Paul et al.. 1,989 western   Screening
1963.     Electric Co. exami"a:ion                         COTOWQ/
U.S.A.    male workers   and                               cases (87)
(148).    participating    history.                   NS   23
        in a prospec-                           l-7    2
        tive study                             8-12      9
       for 455 years.                          13-17      6
                                          18-22   41
                                         23-27      3
                                          >28    9

`Unless otherwise specified, disparities between the total number of mani-
festations and the sum of the individtial smoking categories are due to the
exclusion of either occasional, miscellaneous, mixed, or ex-smokers.

34


morbidity as ,related to smoking (cont.)
manifestations shown in parentheses)!
EX = Ex-smokersl

PROSPECTIVE STUDIES-Continued

Pipes, cigars          Age variation           Comments

All CHD
including EKG
diagnoses.

No data on
NSasa
separate
group.

     30-39    40-49    50-59   t Includes
tLow                       NS, EX, and
SM 1.00(25) 1.00(125) 1.00(157)   <20 cigarettes/
%High                       day.
SM 2.17(10) 0.90 (31) 1.41 (53) $>2OCiga-
                       rettes/day.
                        Includes all
                         CHD but
                         ezcludes
                         death.
                        No data avail-
                       able comparing
                         smokers and
                         nonsmokers.

1.00(53)
1.25(64)

GmmmaTy
  controls
  (1,786)
    33
    7
    11
    12
    30
    2
    6
(P<O.O05)

88 developed
clinical

coronary
disease,
47 angina
pectoris,
28 myocardial
infarction,
13 deaths CHD.

35


studies have shown an increased risk of this manifestation among
smokers, others have not (see table 5).

From these longitudinal st.udies, it has become increasingly clear
that cigarette smoking is one of several risk factors for CHD and
that it exerts both an independent effect and an efiect in conjunc-
tion with the other risk factors. The basic concept may be ex-
pressed as follows: The more risk factors a given individual has,
the greater the chance of his developing CHD. The importance of
the constellation of coronary risk factors which include cigarette
smoking, high blood pressure, and high serum cholesterol in pre-
dicting the risk for CHD is illustrated in figures 1 through 3. Other
risk factors are included in certain of these figures and are dis-
cussed below.

Knowledge of the effects of cigarette smoke on the cardiovascu-
lar system has developed concurrently with the knowledge derived
from the epidemiological studies. Nicotine, as well as cigarette
smoke, has been shown to increase heart rate, stroke volume, and
blood pressure, all most probably secondary to the promotion of
catecholamine release from t.he adrenal gland and other chromaffin
tissue. This release of catecholamines is also considered to be the
cause of the rise in serum free fatty acids observed upon the in-
halation of cigarette smoke. Studies concerning the effect of nico-
tine on cardiac rhythm have also suggested that smoking might
contribute to sudden death from ventricular fibrillation.
In addition, research efforts have also been directed toward the
effects of smoking on blood clotting and thrombosis; since many
cases of sudden death and myocardial infarction are associated
with thrombosis in a diseased coronary artery branch. Cigarette
smoking may be associated with increased platelet aggregation in
vitro and thus might play a role in the development of such throm-
bi or platelet plugs in viva.

Other mechanisms have been investigated. Because cigarette
smoking has been shown in some studies to be related to the prev-
alence of angina pectoris as well as to the incidence of myocardial
infarction, it has been suggested that smoking enhances the de-
velopment of atherosclerotic lesions. Autopsy and experimental
studies have shown that cigarette smoking plays a role in athero-
genesis. The administration of nicotine has been observed to in-
crease the severity of cholesterol-induced atherosclerotic lesions in
experimental animals. Attention is presently being given to carbon
monoxide, which is present in cigarette smoke in such concentra-
tions as to cause carboxyhemoglobin concentrations in the blood
of smokers as high as 10 percent. Based on research in animals,
it is reasonable to conclude that the atherosclerotic process may be
enhanced, in part, by the relative arterial hypoxemia in cigarette

36


A "LIIV, ,
year,
country.

Number and
type of

Data    Follow-up Number
collection year8     of

Cigarettes/day

Cip*l3
and PiPcs

Age variation

comments

reference   Population                   incidents
DOYk    2,282 males.     Detailed      10      Rl    NS  ._ ,_ _. .__. .1.00(30)                                    NS include ex-
et al..    Framingham,    medical                 All  . . .1.09(61)                                      smokers and
1964,    30-62 years     examination             <20 .1.17(16)                                     Pipe and
U.S.A.   of age.        and                    20 .0.99(18)                                      cigal
(54).   1.913 males,      follow-up.     x          >20 . . .1.15(18)                                      smokers.
       Albany.
       39-55 years
       of age,

Jenkins  3,182 males     Initial medical   4%     29    NS  ..l.OO (9)                                     NS include
et al.,    wed 39-69     examination              All current                                                former pipe
1968,    at entru.      and follow-                cigarettes  . ..1.44(16)                                      and ciaal
U.S.A.              up by repeat              >16  ,. ,, ._ ..1.63(14)                                      smokers.
(90).               examina-
                  tion.

KanlWl   5,127 males     Medical       12     107
et al..    and females    examination              NS  
U.S.A.   years of age     and follow-              Heavy SM. .ZO
(94).    30-59         "P.                    cigarette3 . .

NS  
Cigarette SM

  M&8
 1.00 (16)

.2.04(17)
FWLflkl
.1.00(68)
.0.65(16)

   Shapiro  110.000 male    Baseline       3      Total          Males Females    M&8                     M&8      t CP<O.Ol)
    et al..    and female     medical           Unspee- NS  .l.OO    1.00    NS. .l.OO               35-44 45-54 55-64 T(p<0.05)
    1969,    enrollees of     interview           ified  current               SM. .$1.71    NS  .._...... ..l.OO   1 .oo   1.00  NS include
    U.S.A.   New York City   and examina.              cigarettes t1.91    1.20            Current cigawttes .3.40   1.57   2.06    ex-smokers.
    (172).   HIP 35-64      tion and                :40  .1.51]                 <40 ,,,...,,,. ..2.35   1.40   1.54
           years of age.    regular                 >40 . . . . . . ..4.85$   1.20             >40  ., .10.15   2.m   6.15
                      follow-up.                                                           FlWUdC8
                                                                      NS  .l.OO   1.00   1.00
                                                                     Current cigarettes .1.56   1.67   0.97
                                                                      <40  .1,67   1.63   1.04
":                                                                      >40  -   4.12 -

    t Unless otherwise specified, disparities between the total number of     to the exclusion of either occasional, miscellaneous. mixed, or ex-smokers.
   manifestations and the sum of the individual smoking categories are due


smokers caused by the increased carboxyhemoglobin level.

With respect to the acute event of myocardial infarction, atten-
tion has been focused on the role of nicotine. Nicotine stimulates
the myocardium, increasing its oxygen demand. Other experiments
have demonstrated that in the face of diminished coronary flow
(due to partial occlusion from severe atherosclerosis in man or to
partial mechanical obstruction in the animal), nicotine does not
lead to an increase in coronary blood flow as seen in the normal
individual. These effects exaggerate the oxygen deficit when the
supply of oxygen has already been decreased by the presence of
carboxyhemoglobin. Thus, a marked imbalance between oxygen
demand (which has been increased) and oxygen supply (which
has been decreased) is created by the inhalation of CO and nico-
tine. This imbalance may contribute to acute coronary insufficiency
and myocardial infarction.

EPIDEMIO.LOGICAL STUDIES

Numerous epidemiological studies, both retrospective. and pros-
pective, have been carried out in various countries in order to iden-
tify the risk factors associated with the development of coronary
heart disease (CHD) . Many of these studies have included smok-
ing as one of the variables investigated. Tables 2 to 4 present the
major findings.

CORONARY HEART DISEASE MORTALITY

Table 2 lists the various prospective studies concerning the rela-
tion of CHD mortality and smoking. These studies demonstrate the
dose-related effect of cigarette smoking on the risk of developing
CHD. For example, the Dorn Study of U.S. Veterans as reported
by Kahn (93) reveals progressively increasing mortality ratios,
from 1.39 for those smoking 1 to 9 cigarettes per day to 2.00 for
those smoking more than 39 cigarettes per day, Although the data
are not detailed in the accompanying tables, several of these stud-
ies have also shown that increased rates of CHD mortality are
associated with increased cigarette dosage, as measured by the
degree of inhalation and the age at which smoking began. Although
not as striking, the data for females reveal the same trends.

In most studies, the smokers' increased risk of dying from CHD
appears to be limited mainly' to those who smoke cigarettes. Some
studies that have investigated other forms of smoking have shown
much smaller increases in risk for pipe and cigar smokers when
compared to nonsmokers. However, the recent study by Shapiro,
et al. (172) of a large population enrolled in the Health Insurance
Plan (HIP) of New York City showed a significantly increased

38


risk for the development of myocardial infarction and rapidly fatal
myocardial infarction for a group consisting of both pipe and cigar
smokers.

Table 3 details the findings of the American Heart Association
Pooling Project on sudden death. The Pooling Project, a national
cooperative project of the AHA Council on Epidemiology, is de-
scribed in table 1 (88). Cigarette smokers in the 30 to 59 year age
group incurred a risk of sudden death from CHD substantially
greater than that of nonsmokers. Pipe and cigar smokers were
observed to show a risk slightly greater than that of nonsmokers
(table 3).

The relative risk of CHD mortality is greatest among cigarette
smokers (as well as among those with other risk factors) in the
younger age groups and decreases among the elderly. In table 2,
Hammond and Horn found that for those smoking more than one
pack per day, the risk is 2.51 in the 50 to 54 year age group and
1.56 in the 65 to 69 year age group. Although the relative risk for
CHD among smokers decreases in the older age groups, the actual
number of excess deaths among smokers continues to climb
since the differences in death rates between smokers and nonsmok-
ers continue to rise.

CORONARY HEART DISEASE MORBIDITY

Tables 4 and 5 list the prospective studies carried on in a num-
ber of countries to identify the risk of CHD morbidity incurred
by smoking. Here, CHD morbidity includes myocardial infarction
as well as angina pectoris. Certain studies, notably those of Doyle,
et al. (54)) Keys, et al. (111) , and Taylor, et al. (183) include a
number of CHD deaths in their data that could not be separated
out using the information provided in their respective reports.
As noted in the discussion on CHD mortality, the CHD risk ratio
increases significantly as the number of cigarettes smoked per day
increases. Similarly, the HIP data of Shapiro, et al. (I?`?) show
that the elevated morbidity ratios declined with increasing age as
has been shown for mortality ratios.

A recent monograph edited by Keys (111) dealt with the 5-year
CHD incidence in males age 40 to 59 from seven countries. As
summarized in table 4, cigarette smoking was found to be associ-
ated with an increased incidence of CHD in the U.S. railroad
worker population, 2,571 individuals (183). None of the differences
in ratio between smokers and nonsmokers was statistically signifi-
cant for the 13 other population samples which varied in size from
505 to 982 individuals, from the five other countries. (Smoking was
not considered in the two Japanese populations.) When more cases

39


become available to provide greater statistical stability to the rates,
this. intercultural comparison should prove illuminating.

The results of those studies which have separated out angina
pectoris as a manifestation of CHD are presented in table 5. Doyle,
et al. (54) found no relationship between this manifestation of
CHD and cigarette smoking. Both Jenkins, et al. (90) and Kannel,
et al. (94) observed increased risk ratios among male cigarette
smokers although these differences were not statistically signifi-
cant. More recently, Shapiro, et al. (172) found a significantly
increased risk for angina among their male cigarette smokers as
well as increasing risk ratios with increasing dosage among both
males and females, particularly in the younger age groups. A
variety of hypothetical explanations have been advanced to account
for this seeming contradiction. Among these are the relatively
small number of cases, the difficulties associated with the definitive
diagnosis of the syndrome, and differences in the methods of clas-
sifying those cases of angina pectoris which are followed by myo-
cardial infarction.

RETROSPECTIVE STUDIES

Table A 6 presents data from the various retrospective studies
of CHD prevalence. Most of these are case-control studies and show
an increased percentage of smokers among those with clinical CHD
when compared with a selected control population, usually without
apparent CHD. Two of these studies include data on mortality.

THE INTERACTION OF CIGARETTE SMOKING AND
     OTHER CHD RISK FACTORS

The preceding section has reviewed the epidemiologic evidence
which supports the judgment that cigarette smoking is a signifi-
cant risk factor in the development of CHD. Many of the studies
discussed above have identified a number of biochemical, physio-
logical, and environmental factors, other than cigarette smoking,
which also increase the risk of developing CHD. These risk factors
include elevated serum lipids (particularly serum cholesterol) and
hypertension, which, with cigarette smoking, are considered to be
of greatest importance. Other factors are obesity, physical inac-
tivity, elevated resting heart rate, diabetes (as well as asympto-
matic hyperglycemia), electrocardiographic abnormalities, and a
positive family history of premature CHD (88).

A number of these studies have also found that these factors,
when present in the same individual, exert a combined effect on
the risk of developing CHD. Figures 1 through 3 depict this inter-
action of risk factors. As may be noted in Figures 1 and 2, the

40


additional factor of smoking greatly increases the risk of develop-
ing CHD among those people already at high risk because of other
factors.

Furthermore, these studies have shown that the effect of smok-
ing on the risk of developing CHD is statistically independent of
the other risk factors. That is, when the effect of the other factors
is statistically controlled, smoking continues to exert a significant
effect on increasing the risk of developing and dying from CHD.

Smoking and. Serum Lipids

The interaction of smoking and serum lipid levels in the develop-
ment of CHD should be considered in the light of information con-
cerning the relationship of smoking to serum lipid levels. Table A7
presents studies which deal with the association between smoking
and lipids, notably cholesterol, triglycerides, and lipoproteins (con-
cerned with lipid transport). While some of the studies have indi-
cated that smokers show increased serum levels of these lipid con-
stituents, others have not. The populations investigated and the
methods of the various studies show significant variation. This lack
of comparability makes interpretation of the findings difficult.

It is clear, however, that in the presence of high serum choles-
terol, cigarette smoking increases the risk of CHD. Figure 4 de-
picts the data from the Chicago Peoples Gas, Light and Coke Com-
pany study which show that smoking greatly increases the risk of
CHD in each of the cholesterol groups.

Smoking and Hypertension

Some epidemiological studies have indicated that smokers tend
to have lower mean systolic and/or diastolic blood pressures than
nonsmokers, while other studies have not found this to be the case
(table A8). Reid, et al. (155)) in a study of 1,300 British and
American postal workers, found that the blood pressure difference
between the smoking and nonsmoking groups was eliminated after
controlling for body weight.

Tables 9 through 11, derived from the study by Borhani, et al.
(27)) demonstrate the following associations : That for both smok-
ers and nonsmokers, the risk of dying from CHD increases with
increasing diastolic or systolic pressure, and that the risk of mor-
tality from CHD is higher among smokers than among nonsmokers
in each blood pressure group. Cigarette smoking, therefore, has
been shown to elevate CHD mortality independently both of its
effect on blood pressure and of the effect of hypertension on CHD.

Smoking and Physical Inactivity
The recent study by Shapiro, et al. (272) of more than 110,000

41


TABLE 9.-Death rates from coronary heart disease, by systolic blood pressure:
           ILWU mortality study 1951-61

(Coronary heart disease rts classified under IX Code 420)

Smokers

Nonsmokers

              Systolic blood   Person-years    Death    Person-years   Death
   Age group      pleSSure in 1961  of observation    rate'    of observation   rate'

45-54  (130 1,877        27       2.413        8
                 139-149 2,066        34       2,912        l?
                  150-169 740        95       1,177        26
                  >170 369       109        672        45
55-64 . . <130 1,067        84       1.560        26
                  13&-149 1,380        94       2,401       525
                  150-169 647        93       1,558        46
                   >170 524       210       1,117       126

1 Rate per 10,000 person-years of observation.
2 p<O.O25.
3 p<O.Ol
SOURCE: Borhani, N. 0.. et al. (27).

TABLE lO.-Death rates from coronary heart disease, by diastolic
    blood pressure: ILWU mortality study, 1951-61
     (Coronary heart disease as classified under IX Code 420)

Smokers           Nonsmokers

Age group

Diastolic blood  Person-years
pressure in 1951 of observation

Death
rate'

Person-years
of observation

Death
rate'

45-54

55-64

     <@I
    80- 89
    go- 99
    >lOO

     <SO
    80- 89
    9cb 99
    >lOO

1,527        26       1,700        6
2,115        47       2,947        17
961        52       1,507        33
448        89       1.020        20
1.059       104       1.447       221
1,521        59       2,704        15
669       194       1,521       346
369       163        954       147

1 Rate per 10,000 person-years of observation.
2 p<o.o5.
3 P<O.Ol.
SOURCE: Borhani. N. 0.. et al. (27).

TABLE Il.-Death rates from coronary heart disease, among hypertensives and
      nonhypertensires: ILWU mortality study, 1951-61
           (Coronary heart disease as classified under ISC Code 420)

Smokers

Nonsmokers

            Blood pressure      Person-years    Death    Person-years    Death
   Age group      StatUS 1        of observation    rate 2   of observation    rate 2

45-54 _.  Hypertensives    883       125       1.871       "32
          Nonhypertensives   4,169        29       5,303        13
55-64 _.  Hypertensives    931       150       2.219        95
          Nonhypertensives   2,637        93       4.407       3 16

1 According to the WHO recommendation, the following cut-off points are recommended for the
definition of hypertension:

(1) Normotension-below 140190 mm. Hg.
(2) Hypertension-systolic blood pressure 160 mm. Hg. or over, or diastolic 95 mm. Hg. or
over, or both.

(3) Borderline-the residual category. In this analysis. Normotensives and Borderlines were
combined and the population ~8s gr<,npcd into `Nonhypertensives' (1 and 3) and `Hypertensive?
(2).

1 Rate per 10,000 person-years of observation.
3 P<O.Ol.
SOURCE: Borhani, N. O., et al. (7).

42


INCIDENCE
PER 1,000 MEN

80

80-                                          -

70-                                           -

     ALL       NON     NON     NON    SMOKERS   SMOKERS   SMOKERS
            SMOKERS SMOKCRS SMOKERS
            <225    225-274    275 +    <2?5    225-274   275+

CHD     46'         1       5       2       9       16       12
N     1329'       187      235      71      336      317      151
AGE     49         49      50       51      50      49       50

SYSTOLIC
PRESSURE   134

133      136      139      131      133      135

1.19     1.21      1.18     1.12     1.15      1.17

FIGURE 4-Relationship between smoking status and serum cholesterol level
at initial examination, and incidence of clinical coronary heart disease in
men originally age 40-59, free of definite CHD, and followed subsequently
without systematic intervention, Peoples Gas Light and Coke Company
study, 1958-1962.  *For 34 men, no information on smoking status was
available; one of these men had a coronary episode.
SOURCE: Stamler, J., et al. (177).

persons participating in the Health Insurance Plan of New York
City has further identified and elaborated upon the interaction of
the various risk factors. Physical inactivity, both in employment
and during leisure time, was found to be a potent risk factor for
the development of CHD, particularly for rapidly fatal myocardial
infarction.

Figure 5 depicts the effect which smoking exerts on CHD in
combination with physical inactivity. Of note, also, is the observa-
tion that within each activity grouping, smoking greatly increases
the risk of myocardial infarction, thus exerting an independent
effect.

Smoking and Obesity

The analysis by Truett, et al. (190) of the risk factor data from
the Framingham study revealed that weight, while a significant
risk factor, had a considerably smaller effect on CHD incidence
than serum cholesterol, cigarette smoking, or elevated blood pres-
sure. The results concerning the interaction of smoking and obesity
from the San Francisco longshoremen study are shown in table 12.

43


11.0

10.0

9.0

  8.0
%
5  7.0
x
b
s  6.0
E
;  5.0
;
P
g  4.0
K

3.0



2.0



1.0

  Not
dead
within
48 hrs.

Dead
within
48 hrs.

10.89

5.72
(57)

5.18
(46)

Least
active

5.78

4.48
(166)

1.30
(41)

More
active

NONCIGARETTE SMOKERS
  6.33

3.76
(47)

3.03

Least
active

r

MOE
active

Note: Both for cigarette smokers and noncigarette smokers differences between rates among the least
and more active men are statistically sign,ficant for total MI and rapldly fatal MIS at the 0.99 confidence
level. For other MIS the difference is statistically significant only for the nonsmokers (confidence level 0.95).

FIGURE 5-Average annual incidence of first myocardial infarction among men
in relation to overall physical activity class and smoking habits (age-ad-
justed rates per 1,000)
(Actual number of deaths or myocardial infarctions are represented by
figures in parentheses)
SOURCE: Shapiro, S., et al. (-172).

This table shows that cigarette smokers in the 55 to 64 year age
group were observed to have higher CHD death rates than non-
smokers in all weight categories. Similar findings, although not in
all weight groups, were observed for the 45 to 54 year age group.
Cigarette smoking is thus shown to he a CHD risk factor indepen-
dent of body weight.

44


TABLE 12.-Death rates from coronary heart disease avlong men without
abnormalities related to cardiopulmonary diseases by weight classification
        in 1951: ILWU mortality study, 1951-61
        (Coronary heart disease as classified under ISC Code 420)

Age group

Weight
classification 1

       Smokers

Person-years    Death
of observation    rate z

     Nonsmokers

Person-years    Death
of observation    rate ?

45-54  Not overweight , .    388        21        219        I
         Slightly overweight    962        2R       1,096        0
          Moderately overweight   1,383        28       1.574        28
          Markedly overweight    1,055        22       1,197        0
55-64  Not overweight    222        43        247        0
         Slightly overweight    536        15        605        36
          Moderately overweight    855       109       1,320       311
       Markedly overweigh<    735        X8       1,653       312

`The four classes are defined in the text.
2 Rate per 10,000 person-years of observation
3 P<O.Ol.
SOURCE: Borhani, N. O., et al. (271.

TABLE 13.-Death rates from coronary heart disease, by electrocardiographic
      findings in 1951: ILWU mortality study, 1951-61
         (Coronary heart disease as classified under ISC Code 420)

Smokers

Nonsmokers

Age group

Electrocardiographic
findings in 1951

          Death               Death
Person-years          Person-years
of observation   rate 1   of observation    rate 1

46-54 .........  Abnormal ..............    586       102       1,020        39
          Normal  ...............   4,454        38       6.134        15
55-64 .........  Abnormal  .............    583       2.23       1,149        96
          Normal  ...............   3,031        86       6,479       231

1 Rate per 10,000 person-years of observation.
2 P<O.O05.
~O~RCS: Borhani. N. 0.. et al. (87).

TABLE 14.-1958 status with respect to heart rate, blood pressure, cigarette
smoking, and lo-year mortality rates, by cause (1,829 men originally age
     40-59 and free of definite coronary heart disease)
         Peoples Gas Co. Study, 1958-68

1953 risk factor status

Heart
rate

NH
Ii
NH
H
NH
Ii
NH
Ii

All

Cigarette
smoking

  NH
  NH
  NH
  NH
   H
   H
   H
   H

-
     NUl"bCY
     of men

NH        378
NH         45
H        107
H         30
NH        491
NH        127
H        103
H         44

Ten-year mortality. 1968-68

  All causes        CHD
Number   Rate   Number Rate

?1,325

20    '48.3      5    ' 12.0
6    114.9      3    70.3
14    118.3      6    51.8
8    221.6      3    62.0
57    116.8     19    38.9
22    171.1      8    62.3
22    190.4      6    66.0
13    266.4      6    94.9

162    113.2     55     39.4

' Rate per thousand. All =ates are age-adjusted by 5-year age groups to U.S. male population,
1960. High (H) : Heart rate 280; 210 cigarettes per day; diastolic blood pressure 290 mm. Hg.
NH is not high, i.e., below specified cutting points.
`No smoking data available on 4 of the 1,329 me".
~UWE: Berkson. D. M., et al. (43).

45


TABLE 15.-The effect of the cessation of cigarette smoking
         on the incidence of CHD

(Incidence ratios--actual number of cases or events are shown in parentheses)

Author.
Yea=.
count.rY,                   Kesults                      COltllll~ntS
reference

Jenkins

                                           -
                         Ail myocardial
       All CHD events           infarction
Neversmoked  . ..t. 1.00(30)      l.OO(Zl)

et al.,
1968
U.S.A.
(90).

current
cigarette smokers . 2.36(84)
Former
cigarette smokers .2.15 (19 1

            Death from CHD

2.78(68)

2.47(15)

Hammond

    Smoked I-i9 cigarettes/day      Smoked >20
                         cigarettes/day
NWer

and Garfinkel,
1969.
U.S.A.
(76).

smoked regularly . . ,_ .1.00(1,841)
current
cigarette smokers 1.90(1,063)
stopped <l year .1.62  (29)
l-4  .1.22  (57)
5-9  . ,126   (55)
l&19  .0.96   (52)
>20  1. .1.08   (70)
AI1 ex-cigarette smokers .1.16 (263)

l.OO(1.841)   Male data only

2.55 (2.822)
1.61 (62)
1.51 (154)
1.16 (135)
1.25 (133)
1.06  (80)
1.28 (564)

Shapiro
et al..
1969.
U.S.A.
(17s).

Pooling Project,
American Heart
Association
1970.
U.S.A.
(88).

  Total definite myocardial infarction
Never smoked  .................................... .l.OO
Current cigarette smokers  ........................ .1.87
Stopped 25 years ................................. .0.76

        AU CHD deaths
Never smoked ., .1.00(2'7)
>`h pack/day  .1.65(34)
1 pack/day ._ ,... _. .1.70(86)
>l pack/day  .3.00(68)
Ex-smokers  .0.80(19)

First major
coronary event
1.00 (53)   See table 4
1.65 (72)    for description
2.08(205)    of Pooling
3.28(X4)    Project.
1.25 (51)

TABLE 16.-Annual probability of death from coronary heart disease,
in current and discontinued smokers, by age, maximum amount smoked,
            and age started smoking

   Age started smoking
15-W                20-24

Maximum daiLv
number of &a-
r&es smoked

Current
smokers

Discontinued           Discontinued
for five or     Current    for five or
more years    smokers   more years
(Probability X10 s,

56-64   . . ,_.   . .  0           601                 501       -
             lo-20           798        568        811        551
             21-39           969        766        872        698

65-74 1 . .   0          1.015                1.015

lc-20      1;501       1,169     11478       1,213
21-39          1,710       1,334       1,573       1,098

1 For age group 65-14. probabilities for discontinued smokers are for 10 or more years of dis-
continuance since data for the 5-9 year discontinuance group we not given.
SOURCE: Cornfield. J., Mitchell. S. (4.5).
Based on data derived from Kahn, H. A. (93).

46


Smoking and Electrocardiographic Abnormalities

Electrocardiographic (ECG) abnormalities such as T-wave and
ST-segment changes as well as a number of arrhythmias are use-
ful indicators of CHD and may, therefore, be predictive of the
development of clinically overt CHD manifestations. The results
summarized in table IS, from the prospective study by Borhani,
et al. (27), reflect the joint predictive value of smoking and ECG
abnormalities on the death rate from CHD.

Smoking and Heart Rate

Recent analysis by Berkson, et al. (23) of the data derived from
the Chicago Peoples Gas, Light and Coke Company study of
middle-aged men revealed that resting heart rates of 80 or greater
were associated with an increase in the risk of death from CHD.
These authors found that this association was independent of the
other major coronary risk factors.

Table 14 presents i`ne interaction between smoking, blood pres-
sure, and elevated heart rate in increasing the risk of CHD mor-
tality. This study shows that cigarette smoking increases CHD risk
in the presence of elevated heart rate as well as in its absence.

THE EFFECT OF CESSATION OF CIGARETTE
SMOKING ON CORONARY HEART DISEASE

A number of epidemiological studies have been concerned with
the CHD incidence and mortality among ex-cigarette smokers as
Compared with current smokers (51, 76, 88, 90, 93, 172). These
studies are listed in table 15. Table 16 presents the data derived by
Cornfield and Mitchell (45) from the Dorn Study of U.S. Veterans
(93).

Ex-cigarette smokers show a reduced risk of both myocardial
infarction and death from CHD relative to that of continuing ciga-
rette smokers. The Pooling Project (88) and the Western Collab-
orative Study Group (192) which adjusted for the other risk fac-
tors of elevated serum cholesterol and blood pressure observed this
relationship. Hammond and Garfinkel (76) noted that cessation of
smoking is accompanied by a relative decrease in risk of death
from CHD within 1 year after stopping.

This decreased risk of CHD among ex-smokers further strength-
ens the relationship between smoking and CHD. It must be noted,
however, that the group of ex-smokers is composed of individuals
who have stopped smoking for a variety of reasons. Those who
stop because of ,ill health and the presence of symptoms are gen-
erally at high risk and can bias the group results in one direction;

47


those healthy persons who stop as part of a general concern about
their health and may adopt a number of self-protective health prac-
tices are generally at low risk and can bias the group results in the
other direction. Therefore, ex-smokers as a group are not fully
representative of the entire population of smokers and may have
limited value in predicting what would happen if large numbers of
cigarette smokers stopped smoking purely for self-protection. Cer-
tain incidence studies, such as the Pooling Project (88)) were initi-
ated with only clinically healthy individuals. The data from such
studies, as well as those from the British physicians study, contain
ex-smoker data less influenced by these biases.

Fletcher and Horn (63) have recently presented data derived
from the British physicians study of Doll and Hill. Over the past
lo-15 years, cigarette smoking rates among British physicians
have declined significantly in comparison with those of the general
British population. The information presented by these authors
concerning all cardiovascular diseases showed that for individuals
between the ages of 35 and 64, the age-adjusted death rate for CHD
declined by 6 percent among physicians and rose by 10 percent
among the male population of England and Wales during the
period from 1953-57 to 1961-65.

THE CONSTITUTIONAL HYPOTHESIS

The effect of smoking on the incidence of CHD has been found
to be independent of the influence of the other CHD risk factors.
When such risk factors as high serum cholesterol (177)) increased
blood pressure (27)) elevated resting heart rate (23)) physical in-
activity (2 72), obesity (27)) and electrocardiographic abnormali-
ties (27) have been controlled, cigarette smokers still show higher
rates of CHD than nonsmokers.

It has been suggested by some (39, 170) that the relationship
between cigarette smoking and CHD has a constitutional basis.
That is people with certain constitutional make-ups are more likely
to develop CHD, and the same people are more likely to smoke
cigarettes. This hypothesis maintains that the relationship between
cigarette smoking and CHD is thus largely fortuitous and that the
significant relationships are between the genetic make-up of the
individual and CHD and between the genetic make-up of the indi-
vidual and his becoming a cigarette smoker. Two sets of epidemio-
logic data bear on this hypothesis.

It has been maintained that people with a certain temperament
are more likely to smoke and also more likely to develop CHD.
These characteristics have been demonstrated for those with the

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of 1.6, while those in the second group were found to have one of
approximately 1.1. The authors concluded that this difference be-
tween the two groups provides better support for the importance
of constitutional factors as against the importance of cigarette
smoking in the development of angina pectoris.

A similar study was done using the responses of 4,379 U.S. Vet-
eran twin pairs (approximately 60 percent of estimated available
total) who completed the mailed questionnaires (38). Cederlof, et
al. found a significantly increased prevalence of chest pain and
"angina pectoris" among smokers when Group A was analyzed.
Analysis of the smoking-discordant matched twin pairs (Group B)
revealed no association between smoking and cardiovascular symp-
toms among the monozygotic pairs. The dizygotic pair data did
show a slight association. The authors concluded that this lack of
association among the monozygotes and its presence among the
dizygotes and unmatched pairs strengthens the case for a constitu.
tional hypothesis.

A major problem in ,these studies is the small number of cases
available and, therefore, the statistical instability of the results,
In the Swedish study, among the 274 monozygotes, only 19 smokers
and 16 nonsmokers were classified as having angina pectoris while
among the 733 dizygotes, 25 smokers and 25 nonsmokers were so
classified. In neither group was the difference between the prev-
alence ratios found in the Group A analysis and that in the Group
B analysis of statistical significance. Analysis of the data on women
shows a similar lack of significance.

Similar criticisms may be made of the study which utilized the
U.S. Veteran Twin Registry. In that study, the authors observed
that the difference in the prevalence of angina pectoris between
the low-cigarette-exposure and high-cigarette-exposure dizygotic
groups was not present among the monozygotes. The authors ques-
tioned whether the excess morbidity associated with cigarette
smoking found in the dizygotic group was causal as it was not pos-
sible to reproduce the association when studying monozygotic
smoking-discordant twin pairs. As noted above, the numbers in this
study are also small so that the differences in rates do not approach
statistical significance.

Tibblin (288) has questioned the value of a mailed questionnaire
to diagnose heart disease. The questionnaire as originally con-
structed was used and validated by interview technique alone (157,
158). Cederlof, et al. (~$0) conducted a study to determine the
validity of this questionnaire as a mailed instrument by personally
interviewing and examining 170 of the twin pairs who had replied.
Of the eight males who were diagnosed as having "angina pectoris"
by the questionnaire. four were found to be free of symptoms on

50