Alcohol and Nicotine Dependence and Time to Death in a General Adult Population: A Mortality Cohort Study Open Access

Alcohol drinking and tobacco smoking are known to have interactions according to evidence including biological pathways [1] and common genetic grounds [2, 3]. Synergy between alcohol and tobacco consumption has been reported, particularly for diseases of the upper aerodigestive tract [4]. Among patients in addiction treatment facilities whose primary drug was alcohol, 75.2% were found to be tobacco smokers [5]. However, little is known about the co-occurrence of alcohol and nicotine dependence from general population samples with respect to mortality, even though these disorders might act as barriers to quitting smoking and drinking.

In a study involving 6,372 participants in Finland aged 30–70 years, 57% of the participants with alcohol use disorders were also tobacco smokers, whereas only 31% of the total sample smoked tobacco. Both current alcohol use disorders (hazard ratio [HR]: 1.85; 95% confidence interval [CI]: 1.19–2.87) and current tobacco smoking at baseline (HR: 3.38; CI: 2.28–5.01) predicted the time to death 8 years after adjustment for other health disorders, age, and sex [6]. In addition, the time until the first cigarette in the morning after awakening was associated with health disorders [7‒10]. However, less is known about whether the time until the first cigarette may predict the time to death.

One of the limitations of the available evidence is that little is known about potential interaction effects of alcohol and nicotine dependence and the time until the first cigarette in the morning among general population samples, including effects on mortality. Such knowledge could guide practice for interventions and extend lives. Both disorders might have an additive effect on risk of death.

Alcohol and nicotine dependence may have common biological pathways related to disease and death, such as the acetaldehyde pathway [1]. The co-occurrence of alcohol and nicotine dependence might intensify the dose dependence as a risk for early death. Alcohol relapse might also be more likely in the presence of nicotine dependence, and vice versa. We do not know whether stopping smoking or alcohol drinking may affect the time to death if an individual is both alcohol and nicotine dependent. Therefore, the aim of the present study was to analyze co-occurrences of risky alcohol drinking, tobacco smoking, alcohol and nicotine dependence, and the time until the first cigarette in the morning as potential predictors of time to death among adults in Northern Germany.

A random population of adults aged 18–64 years was sampled in the federal state of Schleswig-Holstein, Germany, and stratified by areas of different social structure. The sample included 47 towns or cities [11, 12]. Data on the base sample (n = 6,447) were obtained from the participants’ registration files, which document every resident in Germany and include their addresses and birth dates [13]. However, 618 of the addresses were invalid for reasons such as death or moving out of the sampling area [13].

Among the remaining 5,829 residents, 4,093 (70.2%) interviews had been completed from July 1996 to March 1997, and 4,075 were analyzed [11]. A mortality follow-up was conducted from April 2017 to April 2018. Further details may be found elsewhere [12]. Among the 4,075 baseline participants, vital statistical data could not be obtained for 47 participants, so they were removed from the sample. The final sample for the data analysis comprised 4,028 people (98.8% of 4,075). The analysis was performed on unweighted data because of the representativeness of age groups and sex [13].

At baseline, data about risky alcohol drinking, tobacco smoking, and the criteria for alcohol and nicotine dependence were collected as part of the Munich-Composite International Diagnostic Interview. This standardized interview was performed face-to-face. It had been developed to assess mental disorders including alcohol and nicotine dependence [11, 13]. Each of the participants in the sample was asked whether they had drunk alcohol more than 12 times in life and in the last 12 months prior to the interview. The frequency of drinking was assessed as almost every day, 3–4 times per week, 1–2 times per week, 1–3 times per month, and less than once per month. To assess the quantity of drinking, pictures of different drinks were presented. The study participants were asked how many of each of them they usually drank in 1 day during the last 12 months prior to the interview.

Risky alcohol drinking was assessed based on the frequency and quantity of alcohol consumption, and the levels included alcohol abstainers, low-risk drinkers, hazardous drinkers, and harmful drinkers. Participants who said that they had drunk alcohol 12 times or fewer ever in their life were considered to be alcohol abstainers. Low-risk drinkers were those who drank alcohol at levels below the thresholds for hazardous and harmful drinking. Hazardous alcohol drinkers were those whose consumption was above the thresholds for hazardous drinking (20 and 40 g of pure alcohol per day of the month for females and males, respectively). Harmful alcohol drinkers were those whose consumption was above the thresholds for harmful drinking (65 and 100 g of pure alcohol per day of the month for females and males, respectively). We differentiated both hazardous and harmful drinkers into those who fulfilled the criteria at any time in life before but not in the last 12 months prior to the interview (former hazardous drinkers and former harmful drinkers) and those who did fulfill criteria in the last 12 months (current hazardous drinkers and current harmful drinkers).

Alcohol dependence was diagnosed as part of the interview. The diagnostic criteria according to the fourth edition of the Diagnostic and Statistical Manual of the American Psychiatric Association (DSM-IV) [14] were assessed for both the last 12 months prior to the interview and the time before. Participants who fulfilled the criteria for alcohol dependence ever in life before but not in the last 12 months were considered to have a former alcohol dependence, and those who did fulfill the criteria in the last 12 months were considered to have a current alcohol dependence.

The data on tobacco smoking included smoking status (never, ever less than daily, former daily smoker, current daily smoker of less than 20 cigarettes per day, and current daily smoker of 20 or more cigarettes per day). Those who were considered never smokers answered “no” to the question of whether they had ever smoked tobacco in the form of a cigarette, cigar, or pipe tobacco in their life. Those who were “ever less than daily” smokers reported a history of smoking over a time period longer than 4 weeks at some point in their life but never daily. Former daily smokers were smokers who had disclosed daily tobacco smoking over a time period of more than 4 weeks but not during the last 12 months prior to the interview. Current daily smokers had smoked daily during the last 12 months prior to the interview.

Nicotine dependence was assessed according to the criteria of DSM-IV [14]. As with alcohol dependence, study participants who fulfilled the criteria for nicotine dependence but not in the last 12 months prior to the interview were regarded as having a former nicotine dependence, and those who did fulfill the criteria in the last 12 months prior to the interview were regarded as having a current nicotine dependence. Dependence ever in life was considered as either a former or current dependence. Participants who had smoked cigarettes daily during the last 4 weeks prior to the interview were asked about the time until their first cigarette in the morning after awakening [15‒17]: “How soon after you awake do you smoke your first cigarette?” (within 5 min, within 30 min, within 1 h, after an hour).

Two alcohol-related combined variables were used. The first combined variable was risky alcohol drinking and dependence, and the second was risky alcohol drinking and number of dependence criteria met. We built these variables in a hierarchical manner. In the first step, participants with current alcohol dependence were counted, followed by those with former alcohol dependence. Among the remaining, harmful, hazardous, and low-risk drinkers and alcohol abstainers were considered as separate groups. For risky alcohol drinking and the number of alcohol-dependence criteria met, participants were first counted according to the number of criteria that they had fulfilled previously throughout their lifetimes. Those who did not fulfill the dependence criteria were determined as harmful, hazardous, or low-risk drinkers or alcohol abstainers.

An equivalent procedure was used for two tobacco-related combined variables. The first was tobacco smoking combined with nicotine dependence, and the second was tobacco smoking combined with the time until the first cigarette in the morning. Among those who had never fulfilled the criteria for former or current nicotine dependence, current daily, former daily, ever less than daily, and never smokers were determined. The time to the first cigarette in the morning was estimated among current daily smokers who had smoked cigarettes in the last 4 weeks before the interview. Those who were former daily, ever less than daily, or never smokers were considered as separate groups.

The time to death was assessed as part of the mortality follow-up. Vital statistical data were retrieved from the participants’ registration files at the place of their last residence. For each of the study participants, we recorded whether they were still alive or the date of death.

The data analysis was performed in three steps. First, associations between the two alcohol- and the two tobacco-related combined variables at baseline were calculated with adjustments for age and sex (Table 1). Second, the prediction of the time to death was estimated. In model 1, each of the two alcohol- and the tobacco-related variables was analyzed separately after adjustment for age and sex. In the second model, two variables were included, adjusted for age and sex. Each of the following four pairs of alcohol- and tobacco-related variables were tested: risky alcohol drinking and alcohol dependence and tobacco smoking, risky alcohol drinking and alcohol dependence and tobacco smoking and nicotine dependence, risky alcohol drinking and alcohol dependence and tobacco smoking and time to first cigarette in the morning, risky alcohol drinking and number of alcohol-dependence criteria and tobacco smoking and time to first cigarette in the morning (Table 2). Third, these four pairs of alcohol- and tobacco-related variables were used to define single subgroups of the study participants. For these subgroups, the prediction of time to death was estimated and adjusted for age and sex (Table 3). Reference groups were low-risk drinkers who had been never, ever less than daily or former daily smokers and low-risk drinkers who had never smoked.

For 10 study participants, there were missing data about risky alcohol drinking, which were replaced by the value for low-risk drinking based on 5-year age groups stratified for sex. Low-risk drinkers represented more than 74% of males and more than 81% of females in the different age groups. For 27 of the daily tobacco smokers, the number of cigarettes smoked per day was missing and was replaced by the mean value of the particular age and sex group.

For the description of associations at baseline, proportions and the results of a χ² test are presented (Table 1). For the prediction of the time to death, Cox regression analysis was used. The HRs and 95% CIs are provided (Table 2). The Cox proportional hazards assumption was tested using Schoenfeld residuals [18, 19], and all presented HRs fulfilled this assumption. It was ensured that the number of death cases per predictor variable was 5 or more [20]. All data were analyzed using Stata 17.0 [21].

At baseline, the combination of risky alcohol drinking and dependence was associated with the combination of tobacco smoking and nicotine dependence (χ²: 423.16; p < 0.001) and with the combination of tobacco smoking and the time until the first cigarette in the morning (χ²: 331.95; p < 0.001). Current daily smokers represented 36.82% of the low-risk drinking participants and 77.78% of the participants with current alcohol dependence (Table 1). Furthermore, 44.44% of the participants with current alcohol dependence also had a current nicotine dependence.

The combination of risky alcohol drinking and the number of alcohol-dependence criteria was associated with the combination of tobacco smoking and nicotine dependence (χ²: 386.21; p < 0.001) and with the combination of tobacco smoking and the time until the first cigarette in the morning (χ²: 277.82; p < 0.001). Participants who fulfilled the highest number of alcohol-dependence criteria also had the highest proportion of current daily smokers (86.67%), current nicotine dependence (60.00%), and current smokers who had their first cigarette in the morning in 30 min or less after awakening (60.00%).

The time to death was predicted by both harmful alcohol consumption and current tobacco smoking (Table 2, model 2). Current alcohol dependence was a significant predictor of the time to death (HR: 2.11; CI: 1.23–3.63) in comparison to low-risk drinkers in the model together with tobacco smoking. Current harmful alcohol drinkers who did not fulfill the criteria for alcohol dependence had an HR of 3.01 (CI: 1.91–4.74) compared to low-risk drinkers, even after adjustment for tobacco smoking, age, and sex.

For both alcohol and nicotine dependence, the data in model 2 revealed significantly higher HRs. For current alcohol dependence, the HR was 2.47 (CI: 1.43–4.27) compared to low-risk drinking in model 2 together with current nicotine dependence (HR: 1.82; CI: 1.30–2.56) and never smokers as the reference group. Also, current alcohol dependence predicted the time to death (HR: 1.99; CI: 1.15–3.44 compared to low-risk drinking) in the model together with the time until the first cigarette in the morning (30 min or less; HR: 2.80; CI: 2.07–3.76 compared to never smoking).

The highest number of alcohol-dependence criteria was associated with the highest HR for the time to death compared to low-risk drinkers or abstainers (3.21; CI: 1.69–6.09). Fulfilling five or more criteria for alcohol dependence was a significant predictor of the time to death after adjustment for tobacco smoking and the time until the first cigarette in the morning among current daily smokers. In this model, a time until the first cigarette in the morning of 30 min or less had an HR of 2.66 (CI: 1.98–3.58).

Subgroups of the sample with specific combinations of risky alcohol drinking and tobacco smoking showed particularly high HRs (Table 3). Current harmful alcohol consumers who did not fulfill the criteria for alcohol dependence but were current daily smokers had an HR of 5.81 (CI: 3.31–10.20) for the time to death compared to low-risk drinkers who were never, ever less than daily, or former daily smokers. Individuals with an alcohol dependence ever in life who currently smoked their first cigarette in the morning within 30 min after awakening had an HR of 5.28 (CI: 3.33–8.38) compared to low-risk drinkers who had never smoked.

Former alcohol-dependent participants had an HR of 2.15 (CI: 1.50–3.09) after adjustment for tobacco smoking and nicotine dependence, age, and sex compared to low-risk drinkers. Among former alcohol-dependent participants, 29.59% had a current nicotine dependence. This group had an HR of 4.55 (CI: 2.38–8.70) compared to low-risk drinkers who had never smoked. Furthermore, former alcohol-dependent participants with a former nicotine dependence still had an increased HR for the time to death of 2.81 (CI: 1.33–5.94). Participants who had abstained from alcohol included a particularly low proportion of lifetime nicotine-dependent smokers (13.49%). Among the alcohol abstainers, those who were current daily smokers or had ever been nicotine dependent before had an HR of 4.38 (CI: 2.39–8.04) compared to low-risk drinkers who had never smoked.

This study has four main findings. First, risky alcohol drinking and dependence were associated with tobacco smoking, nicotine dependence, and the time until the first cigarette in the morning in a dose-dependent manner. Second, risky alcohol drinking, tobacco smoking, alcohol and nicotine dependence, and the time until the first cigarette in the morning were independent predictors of the time to death. Third, these predictors seem to add to each other in their potential effect on the loss of lifetime. Fourth, alcohol dependence, even after remission, was related to increased HRs for time to death.

Alcohol dependence had a strong linear association with the proportion of current tobacco smokers. The findings showed that 77.78% of those who had a current alcohol dependence were current daily smokers in our general population sample. This rate is almost equal to the proportion of smokers that has been reported among patients receiving treatment for alcohol dependence [5]. The percentage in our sample seems very high since it may be assumed that treatment is utilized predominantly by severely dependent individuals [22]. In addition, our data revealed a dose-dependent relation between risky alcohol drinking and the proportion of current smokers. A higher level of alcohol consumption (in the range of low-risk drinking to current alcohol dependence) was associated with a higher proportion of current daily smokers. It may be expected that the level of alcohol consumption predicts how large the loss of lifetime will be.

The baseline data suggest that there are subgroups of residents who suffer from a particularly high burden of common risk from alcohol and tobacco. The highest proportion of participants with nicotine dependence ever in life (62.96%) was found among those who had a current alcohol dependence. This is congruent with common biological pathways for alcohol and tobacco, including the acetaldehyde pathway [1] and common genetic grounds [2, 3]. The data support the presence of a common pathology related to the amount of alcohol consumed, alcohol dependence, number of cigarettes smoked per day, and nicotine dependence. Our findings correspond to the conclusion that the time until the first cigarette in the morning might involve other aspects of nicotine dependence [23] than the criteria for dependence of the American Psychiatric Association [14].

The follow-up data on mortality in this study suggest that current harmful alcohol drinking and current daily tobacco smoking, alcohol dependence ever in life, current nicotine dependence, and the time until the first cigarette in the morning may act as five independent predictors of time to death. The data confirm previous findings about the prediction of all-cause mortality [24] and findings from a clinical sample [25]. The high risk of short time to death among harmful drinkers was similar to that among alcohol-dependent individuals, which supports the consideration of harmful drinking as a health disorder that should be treated.

The findings suggest that the effects have a cumulative impact on loss of lifetime from alcohol drinking and tobacco smoking, alcohol and nicotine dependence, and the time until the first cigarette in the morning. The HRs of specific combinations of alcohol drinking and tobacco smoking and of alcohol and nicotine dependence or the time until the first cigarette in the morning appear to be equal to the sum of the HRs from each individual alcohol and tobacco smoking variable after adjustment for age and sex. Among hazardous or harmful drinkers, there seems to be a dose-dependent relation with the time to death compared to low-risk drinkers who were not current daily smokers.

In terms of remission from dependence, the data revealed that both former alcohol and former nicotine-dependent participants had higher HRs. For participants with remission from alcohol dependence, all hazards of early death were increased. Those with remission from nicotine dependence had increased HRs in comparison to low-risk drinkers who had never smoked before.

These findings support the recognition of dependence as a particular burden in terms of lifetime loss. Remission from alcohol dependence seems to be insufficient in decreasing the risk of premature death. Dependence might act as a barrier against stopping alcohol drinking or tobacco smoking. The baseline data revealed that among the participants with current alcohol dependence, 44.44% also had a nicotine dependence, in contrast to the rate of less than 15% among the current harmful or hazardous drinkers. It should be considered that alcohol dependence and harmful or hazardous drinking are highly confounded. However, our data suggest that alcohol dependence provides more information in addition to the frequency and quantity of drinking.

Former risky alcohol drinking or former daily tobacco smoking among participants who were not dependent did not predict a short time to death according to the majority of the results. Compared to low-risk drinkers, neither former hazardous drinking nor former harmful alcohol drinking was associated with an increased HR for dying early in the analysis together with alcohol dependence and tobacco smoking and dependence. This finding supports that the cessation of risky alcohol drinking might be more effective in decreasing the loss of lifetime among individuals who have had no alcohol dependence than among alcohol-dependent individuals. Also, the cessation of daily tobacco smoking among individuals who are not nicotine dependent might be more effective in preserving lifetime than remission from nicotine dependence. These findings support the idea that alcohol and nicotine dependence are particularly severe barriers against quitting alcohol drinking or tobacco smoking.

The time until the first cigarette in the morning was a strong predictor of lifetime loss among current daily smokers. Compared to never smokers, current daily tobacco smokers seemed to have a dose-dependent relation. This is evident in the difference in HR, which was 1.67 (CI: 1.18–2.37) among current daily smokers who smoked their first cigarette in the morning later than an hour after awakening, while it was 2.80 (CI: 2.07–3.76) among those who had their first cigarette in the morning in 30 min or less after awakening. These findings suggest that stopping smoking is more important for maintaining a long life when nicotine is supplied earlier after awakening in the morning. This supports previous findings about the prediction of specific health disorders from the time until the first cigarette in the morning [7‒10].

The data suggest that alcohol abstainers are a group with a particularly high pathology. Their low proportion of current smokers at baseline was similar to that of low-risk drinkers. However, the follow-up data on mortality revealed high HRs for early death. Alcohol abstainers who were current daily or nicotine-dependent smokers had a very high HR of 4.38 (CI: 2.39–8.04) compared to low-risk drinkers who were never smokers. This finding might suggest that alcohol abstainers include particularly high-risk individuals with an unknown morbidity. Health risks from alcohol abstinence and health-protective effects from low-risk drinking have been estimated to be unlikely [26].

The strengths of our study include the random sample of the general population and a satisfactory proportion of participants among the individuals who were eligible for the study. Dependence has been assessed using an internationally standardized interview and the diagnostic criteria of the American Psychiatric Association. Although DSM-IV has been replaced by DSM-5 [27], findings on alcohol dependence are transferable to DSM-5 [28]. Our study has contributed new evidence about alcohol and nicotine dependence as predictors of all-cause mortality in a time frame of 20 years.

The limitations of our study include the use of self-reported data only. Reporting bias is likely. We assume that this is particularly the case for the frequencies and quantities of alcohol drinking. Current and former alcohol dependence were assessed at only one point in time. During the follow-up time, participants with a former dependence may have changed to current dependence, and vice versa. The time span of 20 years also represents a limitation in that many additional factors that may have been relevant in this period could not be assessed. We have not included standardized diagnostic tools such as the Alcohol Use Disorders Identification Test or the entire Fagerstrom Test for Nicotine Dependence, which might have provided different results.

The data from this study have revealed that risky alcohol drinking, tobacco smoking, alcohol and nicotine dependence, and the time until the first cigarette in this general population sample predict the shortening of the time to death. These risk factors may have a cumulative impact on loss of lifetime. Remission from alcohol dependence was insufficient to decrease the hazards of early death in comparison to those of the general population. The findings support expanding the provision of adequate intervention for non-alcohol-dependent hazardous or harmful alcohol consumers and tobacco smokers. The data also suggest that adequate intervention should be provided with respect to both alcohol and tobacco as a standard in routine care.

At the time of the baseline study, no study approval was needed. The Ethics Committee of the University Medicine Greifswald gave approval for the study before the mortality follow-up (BB 044/13). All study participants gave informed consent to participate in the study and had been informed that they were free to withdraw consent at any time. Written informed consent was not needed at the time when the participants had been contacted (i.e., in the years 1996–1997). Consent for publication was part of the informed consent. It was ensured that no individual study participant could be identified in published material. Participant consent was not required for mortality follow-up as it was based on publicly available data.

The authors have no conflict of interest to declare.

This research has been funded by grants from the German Federal Ministry for Education and Research (Grant No. 01 EB 9406) and the German Research Foundation (DFG; Grant No. JO 150/11-1; ME 3180/4-1; RU 1570/3-1). The funding institutions had no role in study design, collection, analysis, and interpretation of the data and writing of the report.

U.J. was involved in the funding, study design, data analysis, and writing of the manuscript. H.-J.R. and C.M. were involved in the funding, contribution to the study design, data gathering and analysis, and writing of the manuscript. M.H. added to the data gathering and analysis and writing of the manuscript. All authors read and approved the final version of the manuscript.

All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.