Cigar Smoking and Death From Coronary Heart Disease in a Prospective Study of US Men FREE

THE NUMBER of cigars consumed in the United States increased by nearly 50% between 1993 and 1996.¹ This rapid increase is particularly striking because it followed a 66% decline from 1964 to 1992.² While cigarette smoking is a well established and important cause of death from coronary heart disease (CHD),³ the potential cardiovascular effects of cigar smoking are unclear. In 1983, a Surgeon General's report concluded that cigar smoking did not appear to substantially increase risk of CHD.³ However, this conclusion was based on studies from the 1950s and 1960s that focused on cigarette smoking and often did not address important issues such as the distinction between current and former cigar smoking or confounding by risk factors such as preexisting heart disease, obesity, and exercise.^4- 6 We examined CHD mortality in a large and more recent study of US men to assess the association between CHD mortality and cigar smoking.

Men in this analysis were selected from the 508 576 male participants in the Cancer Prevention Study II (CPS II), a prospective mortality study of 1.2 million men and women enrolled in 1982 by American Cancer Society volunteers in all 50 US states, the District of Columbia, and Puerto Rico.⁷ Participants completed a baseline self-administered questionnaire in 1982 that included information on demographic characteristics and various behavioral, environmental, occupational, and dietary factors. Women could not be included in the analyses because they were not asked if they smoked cigars. The median age of male participants in 1982 was 57 years; none was younger than 30 years.

The vital status of study participants was determined through December 31, 1991. Two approaches were used to ascertain vital status. Volunteers made personal inquiries in September 1984, 1986, and 1988 to determine whether the participants they had enrolled were alive or dead and to record the date and place of all deaths. Automated linkage by means of the National Death Index⁸ extended follow-up through December 31, 1991, and identified deaths among the 8485 men lost to follow-up between 1982 and 1988. At the completion of follow-up in December 1991, 431 046 men (84.8%) were alive, 76 715 (15.1%) had died, and 815 (0.1%) had follow-up truncated in September 1988 because of insufficient data for National Death Index linkage. Death certificates were obtained for 97.9% of all men known to have died. The underlying cause of death was coded from death certificates according to the International Classification of Diseases, Ninth Revision (ICD-9).⁹ Deaths from CHD were defined as codes 410 through 414.

Cigar smoking status was based entirely on the smoking history reported on the 1982 questionnaire. Men who reported "ever or currently smoking cigarettes, cigars, or pipes, at least one a day for 1 year's time" were instructed to complete more detailed questions about smoking status (current or former), duration (in years), amount (number of cigarettes, cigars, or pipes smoked per day), and depth of inhalation (none, slight, moderate, or deep). Each of these questions was asked separately for cigarettes, cigars, and pipes. Men who reported they were current cigar smokers on the baseline questionnaire were considered "current" cigar smokers, although no information was available about smoking status later during follow-up. To limit misclassification of exposure resulting from current cigar smokers quitting over time, we a priori restricted our analysis to 9 years of follow-up, although additional years of follow-up are now available. Men who reported they had never "smoked cigarettes, cigars, or pipes at least one a day for 1 year's time" were considered "never smokers."

Analyses excluded men who reported that they had ever regularly smoked cigarettes or pipes (n = 364 691), or who had unclear or contradictory responses to smoking questions (n = 125). In addition, we excluded men who reported having had heart disease or diabetes diagnosed (n = 22 482); these 2 diagnoses greatly increase risk of CHD mortality and may also frequently result in smoking cessation. Analyses are based on the remaining 121 278 men.

We used Cox proportional hazards modeling to examine the association of cigar smoking and CHD mortality while adjusting for other potential risk factors. All analyses were stratified by age by using 2 separate data sets, one including only person-time occurring before age 75 years and a second including only person-time occurring at or after age 75 years. The time axis used was follow-up time since enrollment in 1982 or, in the analyses of men younger than 75 years, time since reaching age 75 years if this occurred after enrollment. Age adjustment was accomplished by stratifying on exact year of age at enrollment within each Cox model. All Cox models were also adjusted for alcohol use, body mass index (calculated as weight in kilograms divided by the square of height in meters), education, exercise level, self-reported hypertension, environmental tobacco smoke exposure at home, and use of vitamin C supplements. All remaining variables in Table 1 (race, marital status, fat intake, and vegetable and citrus fruit intake), as well as use of aspirin and of multivitamin, vitamin A, and vitamin E supplements (distributions not shown), were also examined as potential confounders. However, adjustment for these factors had essentially no effect on the risk estimates for current or former smoking. Estimated fat intake and vegetable and citrus fruit intake were derived from items on the 1982 baseline questionnaire that asked about the frequency of consumption of 28 common foods, as has previously been described.¹⁰ All covariates were modeled as dummy variables using the categories shown in Table 1.

The prevalence of current cigar smoking among men in the CPS II cohort was 4.2% at baseline (including current or former cigarette or pipe smokers, who were excluded from this analysis). This prevalence of cigar smoking is slightly less than the 5% to 8% among men older than 45 years reported in US surveys from the 1980s.¹¹

Table 1 shows the distribution of potential CHD risk factors by baseline smoking status. Compared with never smokers, current cigar smokers were slightly less likely to report a college education, high levels of exercise, or use of vitamin C supplements; slightly more likely to report a history of hypertension, high body mass index, or regular alcohol consumption; and considerably more likely to be exposed to environmental tobacco smoke at home.

Table 2 shows the age- and multivariate-adjusted rate ratios for CHD death, comparing cigar smokers with never smokers. Rates of CHD mortality were elevated among current cigar smokers aged 30 to 74 years (rate ratio [RR], 1.30; 95% confidence interval [CI], 1.05-1.62). Rate ratios for CHD mortality were similar for men aged 30 to 64 years (RR, 1.25; 95% CI, 0.89-1.75) and men aged 65 to 74 years (RR, 1.34; 95% CI, 1.01-1.77). Death rates from CHD were not increased among current cigar smokers aged 75 years and older (RR, 0.93; 95% CI, 0.72-1.21) or among former cigar smokers.

As shown by the similarity of the age-adjusted and multivariate-adjusted RRs (Table 2), adjustment for multiple potential confounders had little effect. The strongest confounder was alcohol use. Adjustment for alcohol use increased the RR for current cigar smoking among men younger than 75 years by 7%. Adjustment for all other factors decreased the RRs slightly.

Table 3 shows adjusted RRs for cigar smoking by number of cigars smoked per day, duration of cigar smoking, and self-reported inhalation. Although statistical power was limited, the strongest increases in risk were observed for men who smoked 2 or more cigars per day, had smoked cigars for 25 or more years, or had reported inhaling while smoking cigars.

Because hypertension may modify the effect of smoking, we examined the association between cigar smoking and CHD among men younger than 75 years separately by hypertensive status. The RR associated with current cigar smoking was similar among men without hypertension (multivariate-adjusted RR, 1.35; 95% CI, 1.00-1.82) and hypertensive men (multivariate-adjusted RR, 1.26; 95% CI, 0.93-1.72).

Men aged 30 to 74 years who currently smoked cigars when enrolled had higher risk of death from CHD during the 9-year follow-up. No increased risk was observed for former cigar smokers or the oldest cigar smokers, aged 75 years or older. These results are qualitatively similar to those from numerous epidemiologic studies of cigarette smoking and CHD mortality, which show only small increases in risk for former cigarette smokers, and declining relative risks with increasing age.^3,12- 13

It is biologically plausible that cigar smoking increases risk of CHD. Tobacco smoke from cigars is chemically similar to cigarette smoke,¹⁴ a known cause of CHD.³ Cigar smokers are much less likely to report inhaling than cigarette smokers,^15- 17 possibly because cigar smoke is often more astringent than cigarette smoke as a result of higher levels of free ammonia,¹⁴ or because nicotine from cigars may be absorbed orally without the need for inhalation.¹⁸ Cigar smokers may nevertheless inhale substantial amounts of tobacco smoke. Partly because of their size, cigars produce high levels of environmental tobacco smoke.^14,19 Therefore, even cigar smokers who do not actively inhale are exposed to environmental smoke from their own cigars. Measurements of serum thiocyanate (a marker of tobacco smoke exposure) confirm that cigar smokers inhale a considerable amount of tobacco smoke.¹⁶

Few studies have examined the mechanisms by which cigar (rather than cigarette) smoking might affect CHD. However, there is evidence that cigar smoking, like cigarette smoking, may cause CHD by accelerating atherosclerosis and/or increasing platelet aggregation. Accelerated atherosclerosis was observed in an autopsy study that found greater numbers of aortic plaques among men who had only ever smoked cigars, as compared with never smokers.²⁰ Increased platelet aggregation, which may be associated with substantially increased risk of CHD,²¹ has been observed in studies involving environmental tobacco smoke exposure at levels similar to that which cigar smokers would receive from their own cigars. Nonsmokers sitting for 20 minutes next to cigarette smokers,²² or nonsmokers who were instructed to "smoke" 2 cigarettes without trying to inhale,²³ showed increases in platelet aggregation approximately two-thirds as great as that observed in smokers who had just smoked 2 cigarettes.

The strongest increases in risk of CHD death were observed for current smokers younger than 75 years who smoked 2 or more cigars per day, had smoked cigars for at least 25 years, or reported inhaling while smoking. However, our statistical power was limited, so the importance of smoking frequency, duration, or inhalation patterns cannot be measured precisely. Even relatively low-dose exposures could plausibly increase CHD mortality. Experiments on the effects of environmental tobacco smoke on intermediate markers such as platelet aggregation and endothelial cell damage suggest that some of the biological mechanisms responsible for the cardiovascular effects of tobacco smoke may have low dose thresholds.²⁴

Previous epidemiologic studies of cigar smoking and death from CHD found results generally similar to ours, although our results are the first, to our knowledge, to show an appreciable increase in risk specifically for current cigar smokers. Three cohort studies from the 1950s and 1960s all found slightly increased risk of CHD death among "ever" cigar smokers (current and former cigar smokers combined) who had never regularly smoked cigarettes or pipes.^4- 5,25 The largest of these studies, the American Cancer Society's CPS I cohort, followed up approximately 441,000 men from 1959 through 1963 and found an RR of 1.35 for men aged 55 to 64 years, but no increased risk among men aged 65 years or older.⁵ These studies may underestimate the risk associated with current smoking because, by analogy to cigarette smoking, the strongest effects would be expected among current smokers, with much smaller, if any, effects among former smokers.¹²

Only 1 previous study has separately examined both current and former cigar smoking in relation to CHD mortality among men who had never regularly smoked cigarettes or pipes. The US veterans study followed up more than 293,000 men from 1954 through 1962 and found increased risk among former cigar smokers (RR, 1.41), but not among current cigar smokers (RR, 1.04).⁶ This seemingly paradoxical finding may result from the failure to exclude men with preexisting heart disease. Current smokers who are diagnosed as having heart disease are both more likely to quit smoking (becoming former smokers) and to die of heart disease subsequently. Smoking cessation resulting from cardiovascular disease was documented as early as 1966.²⁶ Such smoking cessation transfers high-risk men with cardiovascular disease out of the category of current smokers and into the category of former smokers. The expected result is to underestimate risks for current smokers and to overestimate risks for former smokers.

The only other study to examine current cigar smoking (but not former cigar smoking) was a recent reanalysis of CPS I,¹⁷ adding additional follow-up to the analysis described above.⁵ This analysis found little overall increased risk of CHD death among current smokers (RR, 1.05; 95% CI, 1.00-1.11), but did find increases in risk among cigar smokers reporting inhalation (RR, 1.37; 95% CI, 1.07-1.75 for "moderate" inhalation) and among cigar smokers younger than 50 years (RR, 1.77; no CI reported). Like the US veterans study,⁶ this analysis may have underestimated any effect of current cigar smoking because it did not exclude men with preexisting heart disease.

Two European studies, a Dutch population-based case-control study²⁷ and a small Danish cohort study,²⁸ both found more than 2-fold increased risk of myocardial infarctions (primarily nonfatal) among current cigar smokers. These relative risks are substantially greater than those that have been observed in the US studies of CHD mortality. This difference in results could reflect differences in the proportion of cigar smokers who inhale or the type of cigars smoked in Europe compared with the United States.

Our study has 2 important strengths compared with previous analyses of the association of cigar smoking with CHD mortality. First, this is the only analysis, to our knowledge, that excluded men diagnosed as having prevalent heart disease and diabetes, diagnoses that greatly increase risk of CHD mortality and may frequently result in smoking cessation. Second, this analysis adjusted for several important CHD mortality risk factors, whereas all previous analyses adjusted only for age.

As in any observational study, confounding by factors related to both cigar smoking and CHD mortality could contribute to either an overestimate or an underestimate of the effect of cigar smoking. Although we adjusted (or determined that adjustment was unnecessary) for several important CHD risk factors, there may be residual confounding by diet or exercise, which were measured relatively crudely. Cigar smokers may also be more likely to have unmeasured characteristics that increase risk of CHD mortality, resulting in an overestimate of the effect of cigar smoking. Alternatively, poorer health may have caused higher-risk current smokers to quit smoking, resulting in an underestimate of the effect of current cigar smoking. Lipids, such as cholesterol, were not measured and could not be evaluated as potential confounders. However, cholesterol may represent an intermediate mechanism through which tobacco smoke causes CHD, rather than a confounder, since cigarette smoking decreases levels of high-density lipoprotein cholesterol, a potent protective factor against CHD.¹²

A considerable proportion of men classified as "current" cigar smokers at baseline may have quit smoking during the 9 years of follow-up. If cigar smoking primarily increases risk acutely, these men would have experienced little increased risk after quitting. Misclassification of current smoking status may therefore have caused us to underestimate the effects of current cigar smoking considerably.

Current cigar smokers in this analysis had never regularly smoked cigarettes, and the great majority had smoked cigars at least daily. Therefore, our results may not be generalizable to 2 groups of cigar smokers, those who have previously smoked cigarettes and those who smoke cigars only occasionally. However, our findings, as well as biological evidence, are consistent with acute effects mediated through thrombosis, so that even occasional cigar smoking may carry immediate risks.

The importance of cigar smoking as a potential emerging public health hazard is illustrated by data from the 1997 Youth Risk Behavior Survey showing 31% of US high school boys and 11% of high school girls had reported smoking a cigar within the past 30 days.²⁹ Although the increased risk of CHD mortality associated with cigar smoking is modest, the public health effect could be considerable given the rapidly rising prevalence of cigar smoking and the fact that CHD remains the leading cause of death in the United States.

Accepted for publication March 23, 1999.

Reprints: Eric J. Jacobs, PhD, Epidemiology and Surveillance Research, American Cancer Society, National Home Office, 1599 Clifton Rd NE, Atlanta, GA 30329-4251 (e-mail: ejacobs@cancer.org).