Smoking and the risk of first acute myocardial infarction

When analyzing risk factors for first acute myocardial infarctlon in the Copenhagen City Heart Study, a large prospective population study of 20,DW men and women, smoking was found to influence risk significantly in a dose-dependent manner, the risk increaslng 2% to 3% for each gram of tobacco smoked daily. Risk was particularly associated wlth inhalation, the risk for inhalers being almost twice that of noninhalers. No difference in risk could be demonstrated between various types of tobacco (pipe, cigar/cheroots, or plain and filtered cigarettes). The rlsk seemed assoctated with current smoking only, inasmuch as the duration of the smoklng habit was not important. Ex-smokers had the same risk as those who had never smoked regardless of duration of smoking and time elapsed since quitting. Relative excess risk was significantly higher in female smokers than in male smokers, and dally alcohol intake appeared to have some protective effect on the risk of first acute myocardial infarction among heavy smokers. (AM HEART J 1991;122:438.)

J#rgen Nyboe, MSc, Gorm Jensen, MD, PhD, Merete Appleyard, RHLT, and Peter Schnohr, MD. Copenhagen, Denmark

In numerous epidemiologic studies smoking has con- sistently been identified as a major risk factor for is- chemic heart disease.1-4 The pathophysiologic mech- anisms responsible for the adverse effect of smoking are by no means clear. The risk seems to be dose de- pendent with regard to the amount of tobacco smoked.4 Most studies are concerned with cigarette smoking only, but the few dealing with other types of tobacco suggest that pipe and cigar smoking may be equally dangerous. 4-6 Some studies have shown that the risk decreases after cessation of smoking, espe- cially in subjects with prior manifestations of is- chemic heart disease,73 8 but the magnitude and rate of this decrease have not yet been determined.g

In this article we present data concerning the prevalence of smoking in a sample of the population of Copenhagen and the role of tobacco smoking as a risk factor for first acute myocardial infarction (AMI). Among current smokers we have examined the risk associated with the amount and type of tobacco smoked including filtered versus plain cigarettes, duration of the smoking habit, and inhalation. Among

From the Copenhagen City Heart Study, Rigshospitalet. Supported by the Danish Heart Foundation and by grants from Laegefor- eningens Forskningsfond, Lily Benthine Lunds Fond, Hafnia-Haand i Haand Fond&, and Fabrikant Mads Clausens Fond. Received for publication Sept. 18, 1990; accepted Jan. 23, 1991. Reprint requests: G. Jensen, the Copenhagen City Heart Study, Depart- ment 7112, Rigshospitalet, Tagensvej 20, DK-2200 Copenhagen, Denmark. 4/l/29665

current nonsmokers we have examined whether ces- sation of smoking has reduced the risk of AMI. Fur- thermore, we have studied whether the effect of smoking on the risk of AM1 differs between men and women and whether it is influenced by daily alcohol consumption.

METHODS Subjects.The Copenhagen City Heart Study is a pro-

spective cardiovascular population study comprising al- most 20,000 men and women, aged 20 years or more, selected at random after age stratification among 90,000 persons living in a defined area around Rigshospitalet, University Hospital of Copenhagen. The persons selected were invited by letter to a health examination at Rigshos- pitalet on a specific date between March 1,1976 and March 31,1978, to collect basic data concerning possible risk fac- tors for each person. A detailed description of the study procedures has previously been published.lO* l1 Informa- tion about new cases of AM1 was obtained from a follow- up examination between 1981 and 83 and through scrutiny of the National Health Service registers of death and hos- pitalization to the end of 1983, that is, a follow-up period of approximately 6.5 years. All cases were verified by means of hospital records and death certificates. Analysis of risk factors is limited to persons aged 30 years or more and comprises 12,196 persons without prior AM1 and 360 cases of first AM1 (Table I).12v l3

Methodology.We have used a regression technique to describe the risk of AM1 during the follow-up period as a function of tobacco smoking as assessed by questionnaire at the initial examination. When the aim is a causative in-

438

Volume 122 Number 2 Smoking and risk of first AMI 439

terpretation of the relationship, it is desirable to eliminate as far as possible the influence of all other risk factors for AM1 that may have affected the smoking pattern; this is accomplished by including variables representing these (confounding) factors in the regression model. We have in- cluded the following possibly confounding factors in the models: age, sex, family history of AMI, earlobe crease, length of school education, income, and marital status.

We have also included in the analysis information about life style factors other than smoking, namely, body mass index (BMI), physical activity during work, and alcohol consumption, as well as systolic blood pressure and plasma total cholesterol concentration, to examine whether there are interactions between the effect of these factors and the effect of smoking.

Collection of data. Systolic blood pressure was mea- sured with subjects in the sitting position, after 5 minutes of rest, by means of the London School of Hygiene sphyg- momanometer. Plasma cholesterol levels were measured in the nonfasting state by means of an enzymatic method. Systolic blood pressure and plasma cholesterol levels were converted to standardized deviates by subtracting the mean and dividing by the standardized deviates for the sex and lo-year age group in question. Earlobe crease was characterized by measuring the length and depth of a pos- sible crease, and BMI was calculated in each person from measured weight and height (weightJheight2, kg/m2). The remaining information was obtained from a questionnaire. Each participant was asked whether his mother or father had had an AMI; if one of these questions was answered affirmatively, that participant was included in the “yes category” for the variable “Family history of AMI.” With regard to education participants were divided into two groups: persons with compulsory schooling only (less than 8 years in school) and persons with more education. Infor- mation about household income was grouped into three categories representing low, medium, and high incomes. Furthermore, participants stated whether they were living with a spouse or living alone. Physical activity at work was classified into four groups according to the subjects’ own assessments. Persons in groups 1 or 2, who were mainly sit- ting or standing and only occasionally walking, were clas- sified as “physically inactive.” The questionnaire included a question about frequency of alcohol intake and in cases of daily alcohol consumption the average number of drinks per day, one drink containing 12 to 15 gm of alcohol.

Participants were asked if they were current smokers, ex-smokers, or had never smoked. Current smokers were asked what type of tobacco they used (plain or filtered cig- arettes, cheroots/cigars, pipe or mixed), the average weekly number of 50 gm pipe tobacco packages and the average daily number of other items smoked, the duration of the smoking habit, and whether or not they inhaled the smoke. The information about the amount of tobacco was con- verted into grams of tobacco consumed per day by using the following conversion factors: 1 cigarette = 1 gm, 1 cheroot = 3 gm, 1 cigar = 5 gm, and one 50 gm package/wk = 7 gm. Ex-smokers were asked about the duration of the smoking habit and the time elapsed since they had stopped.

Table I. Study population for risk factor analysis

Study population Males Females Total

Invited to examination Nonresponders Responders

Subjects aged 20 to 29 yr Subjects with previous AM1 Subjects with missing data

Included in risk factor analysis New cases of AM1 within 7 yr

9,145 10,184 2,634 2,472 6.51 I 7,712

283 327 305 144 276 692

5.647 6,549 260 loo

19,329 5,106

14,223 610 449 968

12,196 360

Biochemical verification of the smoking information was not attempted.

The prevalence of the covariables included in the anal- ysis and the estimated relative risk (ERR) are shown in Table II.

Statietkal analysis. The subject of the risk factor anal- ysis is the hazard or instantaneous rate of a first AMI, and in our analysis we used the Cox regression model for pro- portional hazards.14 The period of observation was counted from the time of the initial examination until the earliest occurence of one of the following: the person had an AM1 (event), died of causes other than AMI (no event), or sur- vived for 7 years or until December 31,X%3, without AM1 (no event). Some of the covariables had only two outcomes, for example, inhalation, and thus could be represented by a binary variable given the values zero (no inhalation) and one (inhalation). Covariables with more than two outcomes were sometimes included directly as a quantitative variable (e.g., BMI) and sometimes represented by means of a number of binary variables, each indicating whether or not the subject belonged to a specific category or had a variable value within a certain interval. Estimates of the regression coefficients were obtained by using the maximum likeli- hood method as suggested by Cox, and the question of whether the AMI hazard was significantly affected by a co- variable was evaluated by means of the likelihood ratio test.

The results of the analysis are presented in terms of ERR, that is, the hazard in the specified group divided by the hazard in a group selected as a basis, For BMI the ERR represents the relative increase in risk for each unit of BMI, which for individuals of normal height represents a weight increase of approximately 3 kg. Similarly the ERR for to- bacco (Table III) relates to an increase of 1 gm of tobacco.

On the basis of the estimated hazard in various groups of smokers relative to nonsmokers, we have calculated the so-called population attributable risk of smoking, that is, the proportion of the AM1 risk that is “explained by” or “may be attributed to” smoking in subgroups of the pop- ulation. The method of calculation is described by Breslow and Day.15

RESULTS Smoking habfts in the sttvdy po9ulstEon. Distribution

of smoking habits3 including the amount of tobacco consumed &n/day) by sex and age are shown in Fig.

440 Nyboe et al.

Table II. Distribution of covariables included in analysis of effect of smoking with estimates of relative AM1 risks

Covariable

Frequency in study

population (%o)

Estimated relative

risk of AMZ*

(F) 30-39 yr 40-49 50-59 60+

(M) 30-39 yr 40-49 50-59 60+

Family disposition Earlobe crease (F) Less than

8yr (M) in school

Income Partner (F) Low No

- Yes Middle No or high Yes

(M) Low No - Yes

Middle No or high Yes

Physical inactivity during work

Daily alcohol intake None 1-2 drinks/day 3-4 drinks/day >4 drinks/day

BMI per unit (kg/m2)

Cholesterol St. deviate < 0.75

2 0.75 Systolic blood pressure

St. deviate < - 0.5 -0.5 to 0.5 >0.5

6.1 1.0 12.6 0.44 20.3 2.6 14.7 8.9

5.7 0.81 11.1 5.9 15.0 14 14.5 26 17.6 1.3 21.8 1.2 26.6 1.2

22.7

9.7 1.5 7.5 2.5 8.4 0.96

28.1 1.0 3.6 1.1 5.9 1.5 5.8 0.93

31.0 1.0

72.6 1.3

72.8 13.6

7.2 6.4

80.6 1.0 19.4 2.0

33.4 1.0 39.7 1.4 26.9 2.0

1.10

1.0 1.0 0.80 0.56 1.015

*From a model including all above-mentioned variables and smoking as given in Table IV.

1. The pattern of smoking is different in the two sexes: among men in the 40- to 59-year age groups approximately three fourths are smokers. In the younger age groups the frequency of smokers is ap- proximately 60%) inasmuch as a greater proportion had never smoked. A similar proportion of smokers is seen in the older age groups, among whom a larger number were ex-smokers. The average amount of to- bacco smoked per smoker is fairly steady, just under 20 gm/day, with a slight decrease among the oldest age groups.

Nonsmokers. The group of nonsmokers consisted of 4406 persons among whom 83 cases of first AM1 were found. In this group 54.8% had never smoked and the remainder were ex-smokers. A binary vari- able characterizing these two groups included in the model containing the 10 covariables mentioned pre- viously was found to be of no significance (x2 = 0.48, df = l), the ERR for ex-smokers being 0.84 with 95 % confidence limits (0.52 to 1.4). Inasmuch as there was no indication that the group of previous smokers had a higher risk of AMI, there was no reason to assume that further subdivision of the ex-smokers would al- ter this result. In fact it was confirmed that the risk did not differ significantly among ex-smokers who had given up the habit less than 1 year previously, 1 to 5 years previously, or more than 5 years previously (x2 = 2.3, df = 2). In subjects who had stopped smok- ing for more than 5 years the ERR was 1.3 (confi- dence limits 0.63 to 2.3) relative to subjects who stopped smoking within the last 5 years.

Similarly subdividing the duration of the smoking habit before quitting into three groups-less than 15 years, 15 to 29 years, or 30 years or more-yielded no significant influence on the risk of AM1 (x2 = 1.2, df = 2) The ERR in subjects having smoked for 30 years or more was 0.97 (confidence limits 0.57 to 1.6) rela- tive to subjects who had smoked for less than 30 years.

Among women in the youngest age groups the fre- Smokers.This group comprised 7790 persons with

Auguet 1991 American Heart Journal

quency of smoking is very similar to that of men. In the 40- to 59-year age groups a slightly higher frequency is seen, although it never exceeded two thirds. In the older age groups the frequency de- creases rapidly, mainly because a large proportion had never started to smoke. The average amount of tobacco smoked per female smoker is nearly the same in all age groups, just under 15 gm/day.

Distributions of smokers according to type of tobacco used and inhalation are shown in Fig. 2. Al- most 10% of the male smokers smoked a pipe, whereas this type of smoking is extremely rare among women. However, cigar/cheroot smoking is quite common in middle-aged women-a peculiar Danish cultural trait. Most female smokers, especially in the younger age groups, smoke filtered cigarettes, whereas the use of plain and filtered cigarettes is equally dis- tributed in male smokers. The great majority of cig- arette smokers inhale. Approximately two thirds of cigar/cheroot smokers deny inhaling, the ratio being somewhat higher in women than in men. Many pipe smokers inhale.

Risk of first AMI. Some of the information about smoking habits pertains only to nonsmokers, some only to smokers, and the preliminary analyses were made within the category in question.

Volume 122 Number 2 Smoking and risk n: first AMI 441

Table III. Estimates of coefficients in three models showing correlation between risk of first AM1 and smoking variables (models contain the covariables given in Table II)

-.- Estimated Standard

Model Variable coefficient error Ratio ERR I__.-

1 Inhalation 0.666 0.158 4.2 1.96 (regardless of type)

Tobacco in grams 0.024 0.0059 4.1 1.024 (regardless of type)

2 Inhalation 0.661 0.172 3.8 i .94 (regardless of type)

Tobacco in grams Plain cigarettes 0.027 0.0084 x2 1.027 Filtered cigarettes 0.018 0.0108 I.7 1.018 Cheroots/cigars 0.024 0.0628 ri.8 1.024 Pipe tobacco 0.020 0.0126 I .6 1.020

3 Inhalation of Plain cigarettes 0.731 0.174 4.2 2.08 Filtered cigarettes 0.550 0.199 2.8 I 73 Cheroots/cigars 0.735 0.240 :i.1 2.09 Pipe tobacco 0.528 0.337 1.6 1.70 Tobacco in grams 0.023 0.0619 3.8 I.023 (regardless of type)

Comparison of models by likelihood ratio test: Model 1 with “full” model: x2 = 8.8, df = 13, 0.8 > p > 0.7. Model 1 with model 2: x2 = 0.99, df = 3, 0.9 > p > 0.8. Model 1 with model 3: x2 = 1.4, df = 3, 0.8 > > 0.7. p

277 cases of AMI. The number of subjects smoking more than one type of tobacco was too small to shed any light on the effect of “mixed smoking.” They were therefore excluded leaving 7286 persons with 251 cases of AMI for the preliminary analysis. In this analysis it was assumed that the relationship between the logarithm of the AM1 hazard and the amount of tobacco smoked daily is linear, that is, may be char- acterized by an intercept and a slope.

We first fitted to the data a detailed model de- scribing the relationship between the AM1 hazard and the amount of tobacco smoked (in grams/day) separately for each of eight groups of smokers char- acter&d by type of tobacco used (plain cigarettes, filtered cigarettes, cheroots/cigars, or pipe tobacco) and by inhalation (yes or no). This model contained 15 “smoking variables” (eight for slopes and eight minus one for intercepts) in addition to the covari- ablee given in Table II. By comparing this model with simpler models for smoking, it was found that the typeof tobacco had no statistical significance, whereas the amount of tobacco and inhalation were both highly sign&ant. In fact the likelihood ratio test for comparison of the preceding “full” model with a model containing only one slope and one intercept for inhalation showed x2 = 8.8 for df = 13, that is, there was no significant loss of information with the use of the reduced model (Table III). Table III also gives results for two more detailed models, one containing

different slopes for each type of tobacco (model 2) and the other containing different inbmxpb for each type of tobacco (model 3). Thus we were unable to demonstrate significant differences between the ef- fects of different types of tobacco, but the uneer- tainty of the estimates does not preclude the exist- ence of considerable differences.

Next we investigated whether the duration of the smoking habit had an influence on the risk of AMI. When a variable representing the years was added to the simple m amoung of tobacco and inhalati icant at the 5% level (x2 = 0.2, df = 1). The same conclusion was reached when the duration of smok- ing was represented by binary varia&s representing groups: 1 to 14 years, 15 to 29 years, and 30 or more years (x2 = 3.3, df = 2). The ERR in subjects who had smoked for 20 years or more was V,% (confidence limits 0.46 to 1.3) relative to subjects who had smoked for less than 20 years. Thus we were unable to dem- onstrate a relationship between the risk of AMI and the duration of smoking in the past.

Population mod&s. The results of the preceding analyses were combined in a model cable to the entire population. In this model the smoking data were represented by means of six b&q variables characterizing noninhalers amok& less than 15 gm/ day, noninhalers smoking 15 to 29 g&day, nonin- halers smoking 30 gm/day or more, and three similar

442 Nyboe et al. August 1991

American Heart Journal

Fig. 1. Smoking habits in Copenhagen City Heart Study population by sex and age.

variables for inhalers in relation to nonsmokers. The ERR obtained with this model are shown in Fig. 3.

The risk of AM1 is lowest among nonsmokers, it increases exponentially with the amount of tobacco smoked, and for a given amount of tobacco the risk is nearly twice as high among inhalers as among non- inhalers. In Fig. 3 the smoking groups are represented on the horizontal scale in accordance with their dis- tribution in the study population; this representation shows that the major part of the attributable risk of smoking (see below) comes from the inhalers.

To examine whether the effect of smoking interacts with the effect of other factors, it was necessary to simplify the model, namely, to disregard the amount of tobacco among the noninhalers. With this simpli- fied model we found a stronger effect of smoking rel- ative to not smoking among women than among men (Table IV). The estimated difference between the risks in men and women increased consistently with

increasing smoking intensity, and the difference was statistically significant at the 5% level in the three groups of smokers who inhaled. The difference be- tween the sexes appears convincing, although the overall comparison of the models with and without interaction terms did not show a significant differ- ence at the 5% level.

We also studied the effect of smoking separately for persons with and without daily alcohol intake. A significant interaction was found between the two factors (Table V). Whereas the risk of AM1 increased sharply with inhalation and with increasing amounts of tobacco among persons without daily intake of al- cohol, the increase was much less among daily drink- ers. Among the heaviest smokers the risk of AM1 was significantly lower among persons drinking alcohol daily than among those not doing so. On the other hand, the difference in the opposite direction be- tween the risks in the corresponding groups of non-

Volums 122 Number 2 Smoking arrd r&k of first AMI 443

Fig. 2. Use of different types of tobacco smoked and inhalation among smokers in Copenhagen City Heart Study by sex and age. Shaded areas of columns represent subjects who inhaled.

smokers was not statistically significant at the 5% level.

We have not been able to demonstrate any inter- action between the effect of smoking and the effects of BMI or physical inactivity during work. Neither could interactive effects of smoking and systolic blood pressure, respective smoking, and total plasma cholesterol concentration be demonstrated (Tables VI and VII).

Attribwtable risk. Based on the ERRS given in Table IV and the distributions of the five smoking groups in each sex and lo-year age group, we have calculated the estimated attributable risks shown in Table VIII. The proportion of the AM1 risk that can be attrib- uted to smoking is for women and men of all ages 0.59 and 0.38, respectively. Although women generally smoke less than men, their higher relative risks result in higher attributable risks in all age groups. In both

sexes the attributable risk is lower among persons more than 60 years of age than among younger per- sons, because there are fewer smokers and fewer in- halers in the oldest age group.

DISCUSSlOW

The Copenhagen City Heart Study has confirmed the strength of the “classical” coronary risk factors,‘2,‘3 and particularly the role of tobacco smoking as a major risk factor for AMI. In the present study some new facets have been added to the picture.

Previous observations that the risk depends on the amount of tobacco smoked are con&m&, and the present analysis confirm@ that the habit of inhaling the smoke also plays a very important role. In fact it appears that smoking a considerable amount of tobacco leads only to a modest increase in the risk of

444 Nyboe et al. Augurt 1991

American Heart Journal

Fig. 3. Estimated effects of tobacco smoking on risk of first AMI. Horizontal scale represents distribution of smoking groups in study population.

Table IV. Estimated effect of tobacco smoking on risk of AM1 among females and males

Smoking group

Nonsmokers Noninhalers Inhalers

1-14 gm/day 15-29 gmjday 130 gm/day

Relative risk of first AZdZ among

Females Males

1.0 1.0 1.5 1.2

3.6 1.6 4.6 2.1 9.4 2.9

Comparison with model without interaction term: x2 = 9.3, df = 4, 0.1 > p > 0.05.

AMI, provided that the smoke is not inhaled. On the other hand, inhalation always results in a consider- ably increased risk, even for a small amount of tobacco consumption.

Our data suggest that the type of tobacco used is unimportant; filtered cigarettes and pipes are as dangerous as plain cigarettes and cigars/cheroots.

This finding is in agreement with those of other studies on pipe and cigar smoking,5y 6 although other studies on filtered versus plain cigarettes show small inconsistent differences.16-I8 It should be recognized that smoking habits with regard to the amount smoked and inhalation may be profoundly affected by the type of tobacco smoked and, because many more pipe and cigar smokers did not inhale, a case could still be made for persuading inveterate ciga- rette smokers to switch to pipe smoking. Pipe smok- ers tend to consume less tobacco because of the higher nicotine content of pipe tobacco.iQ On the other hand, inhalers changing to another type of to- bacco are likely to continue to inhale.

Inhalation seems to be the major determinant of the dose-dependent risk in smokers, but even nonin- halers experience a dose-dependent risk. This may be partly explained by underreporting of inhalation, but it should be noted that “passive smokers,” that is, nonsmoking subjects exposed to tobacco smoke, are also at increased risk for AMI.

The risk of AM1 in nonsmoking women is much

Volume 122 Number 2

Table V. Estimated effect of tobacco smoking on risk of Table VII. Estimated effect of tobacco smoking on risk of AM1 according to alcohol consumption AM1 according to level of total cholesterol

Relative risk of first AMI according

to frequency of alcohol consumption

Smoking group

Not daily Daily

Nonsmokers Noninhalers Inhalers

I 14 gmlday 15-29 gm/day ~30 gm/day

1.0 1.5 1.5 1.4

2.6 2.1 3.1 2.6 6.7 2.0

Comparist~nwithmodel without interaction term:~* = 13.5,df = 4,~ < 0.01.

Table VI. Estimated effect of tobacco smoking on risk of AMI according to systolic blood pressure

Smoking group

Relative risk of first AMI according to level of

systolic blood pressure Standardized deviate

<-0.50 -0.50 to 0.50 .0.50

Nonsmokers 1.0 1.0 1.0 Noninhalers 1.4 1.3 1.3 Inhalers

l-14 gm/day 1.7 2.5 2.0 15-29 gm/day 2.3 2.5 3.1 ~30 gm/day 3.6 4.5 3.3

Gnnparison with model without interaction term: x2 = 3.0, df = 8, p 1 0.1

lower than that in nonsmoking men. However, the relative excess risk from smoking is much higher in women than in men. The high risk in female smokers in this study is comparable to the findings in other recent studies21p 22 but is in contrast to the findings of the Framingham study. 23 The Framingham study contains no data on inhalation, and the discrepancy may be due to culturally and secularly determined differences in inhalation habits.

In this context the increasing tobacco consumption in young Danish women must cause grave concern. Although the proportion of Danish boys who start to smoke is declining, the proportion of smokers among girls and young women is by contrast increasing, and the heaviest smokers in a few years may be women.24 The explanation for this development is obviously very complex and relates to societal changes in the last few decades. Similar patterns have emerged in many other European countries. If left unchecked the development described here may cause a reversal of

Smoking

group

Relative risk of p’rst AM1 according

to level of tota! cholesterol Standardized derxato

~I- -

<o. 7<5 $ z 0 75

Nonsmokers Noninhalers Inhalers

1-14 gm/day 15-29 gmlday ~30 gm/day

Comparison with model without int~eraction term: xi = 5.9, df = 4, p > il.1

Table VIII. Estimated proportion of AM1 risk at,tributable to smoking

l__-_l--- Age groups

iyr) FernalPs A4ales

30-39 40-49 50-59 60+

All ages

0.67 0 40 0.66 cj.43 0.60 0.40 0.42 0.29 0.59 0,:1s

^~_l-

the male preponderance with regard to coronary heart disease.

In studies of lung cancer it has been shown that the risk is associated with cumulative tobacco consump- tion through life16; consequently a life history of smoking habits is mandatory in such studies. Ob- taining a life history of smoking in studies pertaining to ischemic heart disease may in contrast not be as important. The role of smoking in the development of ischemic heart disease is probably of an entirely different nature, since the risk seems to be related to current smoking only. Most prospective epidemo- logic studies show very little or no association be- tween antemortem-determined smoking habite and postmortem-determined coronary atherosclerosis of the coronary arteries.w On the other hand, results of coronary arteriographic studies seem to show a some- what higher rate of coronary artery disease in pa- tients who smoke compared with those who do not,26t 27 a finding that may reflect a selection bias not present in epidemiologic studies. The role of smoking in preexisting coronary disease must consequently be related to the acute chain of events leading to plaque rupture, thrombus formation, and development of AMI. The biochemical effects of smoking lend cre- dence to this concept. Smoking has a slight adverse

446 Nyboe et al.

effect on lipid patterns in that it causes a decrease in the concentration of HDL8 cholesterol,28 but this in- fluence is not sticient to explain the adverse effect of smoking.29

On the other hand, smoking has a marked effect on clotting factors (fibrinogen and platelet function) and endothelium function, which have been inde- pendently associated with risk.30-32 Our results sup- port this concept of the role of smoking, inasmuch as the risk in ex-smokers is similar to the risk in those who have never smoked, regardless of the duration of smoking and the time elapsed since quitting. Sup- portive evidence for this concept appears also in cur- rent smokers, inasmuch as the duration of smoking seems unimportant with regard to the risk of AM1 and in clinical follow-up studies showing rapidly de- creasing risk in patients with coronary heart disease who quit smoking. 7* 8, 27 Obviously the low incidence of AM1 in nonsmokers and the fairly small proportion of the sample that had quit smoking reduces the sta- tistical power to detect small differences in risk be- tween various groups of ex-smokers. The lack of any trend and the consistency of the results, however, support our contentions.

We have previously reported that there is a rela- tionship between the risk of AM1 and alcohol intake, the risk decreasing with the increasing number of drinks taken daily (up to five) and being highest among persons not drinking alcohol daily.13 This finding is consistent with the results of several other studies.22l 2g* 33p 34 On the basis of the more detailed analysis given here, it seems that this “protective” effect of alcohol is limited to heavy smokers.

Our findings with regard to diminution of risk af- ter quitting are encouraging, somewhat in contrast to the British Regional Heart Study.g Our findings sug- gest that quitting smoking or, if it is impossible to stop, reducing the amount of tobacco smoked and abandoning inhalation may reduce the risk of first AMI.

REFERENCES

1.

2.

3.

4.

5.

United States Department of Health and Human Services. Cardiovascular disease. A report of the Surgeon General. The health consequences of smoking. Public Health Service; 1983. Kannel WB, McGee DL, Castelli WP. Latest perspectives on cigarette smoking and cardiovascular disease: The Framing- ham study. J Cardiac Rehabil 19&4;4:267-77. Doll R, Pete R. Mortality in relation to smoking: 20 years’ ob- servation on male British doctors. Br Med J 1976:2:1525-36. Pooling Project Research Group. Relationship of blood pres- sure, serum cholesterol, smoking habit, relative weight and ECG abnormalities to incidence of major coronary events: final report of the Pooling project. J Chron Dis 1978;31:201- 306. Gyntelberg F, Lauridsen L, Pedersen PB, Schubell K. Smok- ing and risk of myocardial infarction in Copenhagen men aged

August 19Sl Amerkan Heart Journal

40-59, with special reference to cheroot smoking. Lancet 1981;1:987-9.

6. Carstensen JM, Pershagen G, Eklund G. Mortality in relation to cigarette and pipe smoking: 16 year observation of 25,000 Swedish men. J Epidemiol Communitv Health 1987;41:166-

7.

8.

9.

10.

11.

12.

13.

14.

15.

16.

17.

18.

19.

20.

21.

22.

23.

24.

25.

26.

27.

28.

72. Gordon T, Kannel WB, McGee D, Dawber TR. Death and coronary attacks in men after giving up cigarette smoking. A report from the Framingham study. Lancet 1974;1:1345-8. Mulcahy R. Influence of cigarette smoking on morbidity and mortality after myocardial infarction. Br Heart J 1983;49: 410-5. Cook DG, Pocock SJ, Shaper AG, Kussick SJ. Giving up smoking and the risk of heart attacks. A report from the Brit- ish Regional Heart Study. Lancet 1986;2:1376-80. Jensen G. Epidemiology of chest pain and angina pectoris, with special reference to treatment needs. Acta Med Stand 1984;(suppl) 682:1-120. Appleyard M, ed. The Copenhagen City Heart Study. @sterbroundersdgelsen. A book of tables with data from the first examination (1976-78) and a five year follow-up (1981- 83). Stand J Sot Med 1989;(supp1)41. Nyboe J, Jensen G, Appieyard M, Schnohr P. Risk factors for acute myocardial infarction. I: Hereditary, educational and socioeconomic factors. Eur Heart J 1989;10:910-6. Jensen G, Nyboe J, Appleyard M, Schnohr P. Risk factors for acute myocardial infarction. II. Smoking, alcohol intake, physical activity, obesity, oral contraception, diabetes, lipids, and blood pressure. Eur Heart J 1991;12:298-308. Cox DR. Regression models and life-tables. J R. Stat Sot (B) 1972;35:187-220. Breslow NE, Day NE. In: Statistical methods in cancer research. 1980; ~011. Lyon: International Agency for Research on Cancer, 1980:73-5. Higginbottam T, Shipley MJ, Rose G. Cigarettes, lung cancer, and coronary heart disease: the effect of inhalation and tar yield. J Epidemiol Community Health 1982;36:113-7. Hammond EC, Garfinkel L, Seidman H, Lew EA. “Tar” and nicotine content of cigarette smoke in relation to death rates. Environ Rea 1976;12:263-74. Castelli WP, Dawber TR, Feinlieb M, Garnison RJ, McNa- mara P, Kannel WB. The filter cigarette and coronary heart disease: the Framingham study. Lancet 1981;2:109-13. Wald NJ, Idle M, Boreham J, Bailey A, Vukanis HV. Serum cotinine levels in pipe smokers: evidence against nicotine as cause of coronary heart disease. Lancet 1981;2:775-7. Helsing KJ, Sandier DP, Comstock GW, Chee E. Heart disease mortality in nonsmokers living with smokers. Am J Epidemiol 1988;127:915-22. Willet WC, Green A, Stampfer MJ, et al. Relative and abso- lute excess risk of coronary heart disease among women who smoke cigarettes. N Engl J Med 1987;317:1303-9. La Vecchia C, Franceschi S, Decarli A, Pampallona S, Tognoni G. Risk factors for myocardial infarction in young women. Am J Epidemiol 1987;125:832-43. Seltzer CC. Framingham study data and “established wisdom” about cigarette smoking and coronary heart disease. J Clin Epidemiol 1989;42:743-50. Nielsen PE. Zacho J. Olsen JA. Olsen CA. AEndrinrrer i dan- skernes rygevaner 1970-1987. Ugeskr Laeger 1988;15&2229-33. McGill HC. The cardiovascular pathology of smoking. AM HEART J 1988,115:250-7. Vander Zwaag R, Lemp GF, Hughes JP, et al. The effect of cigarette smoking on the pattern of coronary atherosclerosis. Chest 1988;94:290-5. Vlitstra RE, Kronmal RA, Oberman A, Frye RL, Killip III T. Effect of cigarette smoking on survival of patients with angio- graphically documented coronary artery disease. Report from the CASS Registry. JAMA 1986;255:1023-7. Mjjs OD. Lipid effects of smoking. AM HEART J 1988;115: 272-5.

29. Criqui MH, Cowan LD, Tyroler HA, et al. Lipoproteins as

Volume 122 Number 2 Smoking and risk of first AMI

mediators for the effects of alcohol consumption and cigarette smoking on cardiovascular mortality: results from the lipid research clinics follow-up study. Am JEpidemiol1987;126:629- 37.

30. Kannel WB, D’Agostino R, Belanger AJ. Fibrinogen, cigarette smoking, and risk of cardiovascular disease: insights from the Framingham study. AM HEART J 1987;113:1006-10.

31. Felts JD, Bonebrake FC. The effects of cigarette smoke and nicotine on platelet thrombus formation in stenosed dog cor- onary arteries: inhibition with phentolamine. Circulation 1982;65:465-70.

32. Meade TW, Imeson J. Effects of changes in smoking and other characteristics on clotting factors and the risk for ischaemic heart disease. Lancet 1987;2:986-8.

33. Stampfer MJ, Golditz GA, Willet WC, Green A, Speizer FE, Hennekens CH. A prospective study of moderate alcohol con- sumption and the risk of coronary disease and stroke in women. N Engl J Med 1988;319:267-73.

34. Scragg R, Stewart A, Jackson R, Beaglehole R. Alcohol and exercise in myocardial infarction and sudden coronary death in men and women. Am J Epidemiol 1987:126:77-85.

coronary arbry: ia 83 patkmts with

at the ieft aortic sinus

Among 20,332 ad&t pationte who underwent consecutive cord&c t awl ccwonffy arterio$rPphy, 83 (0.4%) w%r% angto(H%phic%iiy identified %a h%vi%g main coronrry artery. Th% angloi&r%phle char%cteri%ticr of thi% coronary anomaly in&de: (1) the pre%%nc% of two weilwpar%ted mmnary o&la at the ieft aortic sinus reeuttkg hr aep%r%t% or&hi of the i8ft enterior de%ceMi%fj md ciroumftex erterieq (2) an domiaanoe; (3) % h&her (6%) than usual (0.5% to 1. of a hi@ irmidence of congefkitai he%rt anomaiies; an coron%ry artery dSntw4 str%ii%r to that of patients whose ieft m&n artery ta t&a&. irk SU% of the pati%nts dWi@uftie6 in uteotiveiy cannuiating the separate oHi%m of the otrix%Ht%x adequ%t%iy oprcifying this v%s%%i reButted in % need to ch%n RecegMton of thir coronary anomaly in needed to en%ur% and III impert%nt for prtierkts under@ng cardiac surgery to seiectkeiy perfu%e the%e sep%r%te vessels during cardiopulmonery bypass. (AM HEART J 1991;122:447.)

On Topaz, MD, German0 DiSciascio, MD, Michael 3. Cowley, MD, Ariel Soffer, MD, Patricia Lanter, MS, Evelyn Goudreau, MD, Amar Nath, MD, Mark Warner, MD, and George W. Vetrovec, MD. Richmond, Vu.

Congenital absence of the left main coronary artery with the presence of two well-separated ostia result- ing in origin of the left anterior descending and cir- cumflex arteries directly from the left sinus of Val-

From the Cardiac Catheterization Laboratory, Division of Cardiology, Medical College of Virginia. Received for publication Nov. 21, 1990; accepted Jan. 4, 1991. Reprint requests: On Topaz, MD, Division of Cardiology, Case Western Reserve University, University Hospitals of Cleveland, 2074 Abington Rd., Cleveland, OH 44106. 4/l/29864

salva is considered a rare anom& d theleft coronary circulaticm, with an esthntrfprd i the registry tories at the adult cases with an absent left main coronary artery

the left aortrc smus, w

tion of an absent left main coronary &ery wmy affect clinical management, its recognition is warranted.

447