Alcohol consumption and mortality in Serbia: twenty-year follow-up study.
ABSTRACT To investigate the connection between alcohol consumption and general and specific mortality in the Serbian population.
Total of 286 healthy middle-aged participants of both genders enrolled in a prospective follow-up study in 1974. During the following 20 years, 80 deaths occurred. The data on underlying causes of death were obtained from official death certificates. Alcohol consumption was estimated from a multiple-choice questionnaire. According to the total daily alcohol intake, subjects were classified into 3 groups: none- or rare drinkers, moderate, and heavy drinkers. The relative risks (RR) adjusted for gender, smoking, body mass index, and blood pressure were calculated using non-drinkers as a reference category.
Heavy drinkers exhibited significantly higher adjusted ratios for all-cause mortality (RR=1.970, 95% confidence interval [CI]=1.062-3.651; p=0.031) and myocardial infarction (RR=2.463, 95% CI=1.050-5.775; p=0.038), and non-significantly higher risk for death from other causes. Moderate drinkers exhibited lower adjusted risk ratios for all-cause mortality, myocardial infarction and death from other causes, but this decrease did not reach the significance level. Further, overall probability of survival at every time point was the highest among moderate drinkers and lowest among heavy drinkers.
Among Serbian middle-aged population moderate alcohol consumption reduced mortality from all causes, myocardial infarction and other causes of death, and increased the probability of survival in a twenty year follow-up period. Heavy drinking increased mortality rates from all causes and reduced the twenty year-survival probability in comparison with non-drinkers.
- SourceAvailable from: stroke.ahajournals.org[show abstract] [hide abstract]
ABSTRACT: Stroke is a major cause of death in the United States. The association between alcohol consumption and ischemic stroke (IS) remains controversial. We used data collected on participants in the Framingham Study to assess the association between total alcohol intake and type of alcoholic beverage and development of IS, overall and according to age. A total of 196 men and 245 women developed IS during three 10-year follow-up periods. In the categories of never drinkers, drinkers of 0.1 to 11, 12 to 23, and > or =24 g/d of ethanol (a "typical drink" is approximately 12 g of ethanol), and former drinkers of 0.1 to 11 and > or =12 g/d, crude incidence rates of IS were 6.5, 5.9, 4.9, 5.0, 6.7, and 17.8 cases per 1000 person-years, respectively, for men and 5.9, 4.1, 4.1, 4.3, 8.3, and 7.1, respectively, for women. Overall, compared with never drinkers in a multivariate Cox regression, current alcohol consumption was not related significantly to IS in either sex. Former drinking of > or =12 g/d of alcohol was associated with a 2.4 times higher risk of IS among men but not among women. When stratified by age, alcohol intake was associated with lower risk of IS among subjects aged 60 to 69 years. In beverage-specific analysis, only wine consumption was related to a decreased risk of IS. Our data showed no significant association between total alcohol and IS overall but showed a protective effect of alcohol among subjects aged 60 to 69 years.Stroke 04/2002; 33(4):907-12. · 6.16 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: To evaluate prospectively the effect on mortality of wine drinking in Eastern France, we conducted an analysis on 34,014 consecutive middle-aged men coming for a comprehensive health appraisal between 1978 and 1983. We evaluated education, physical activity, smoking, and drinking habits by a questionnaire. Electrocardiogram, blood pressure, serum total cholesterol, and gamma-glutamyltransferase level were routinely measured. Seventy-seven per cent of the subjects drank wine; there was little difference between social classes in this proportion. We evaluated mortality over 10-15 years of follow-up. We estimated the relative risk (RR) of death by Cox proportional hazard models using nondrinkers as the reference and adjusting for six covariables. For an intake of 22-32 and 33-54 gm of alcohol per day, the RR of all-cause death was 0.70 [95% confidence interval (CI) = 0.59-0.82] and 0.76 (95% CI = 0.66-0.87), respectively. The lower mortality resulted from fewer deaths from cardiovascular disease and cancer. Above 128 gm per day of alcohol consumption, the RR was 1.37 (95% CI = 1.16-1.61). A moderate intake of wine (2-5 glasses per day) was associated with a 24-31% reduction in all-cause mortality, a proportion that was similar for smokers, ex-smokers, and nonsmokers.Epidemiology 03/1998; 9(2):184-8. · 5.74 Impact Factor
- BMJ 10/1991; 303(6802):565-8. · 14.09 Impact Factor
Alcohol Consumption and Mortality in Serbia: Twenty-year Follow-up Study
Branko Jakovljeviæ, Vesna Stojanov1, Katarina Paunoviæ, Goran Belojeviæ, Nataša Miliæ2
Institute for Hygiene and Medical Ecology, Belgrade University School of Medicine;1Institute for Cardiovascular
Diseases, Clinical Center of Serbia; and2Institute for Medical Statistics and Informatics, Belgrade University School
of Medicine, Belgrade, Serbia and Montenegro
Aim. To investigate the connection between alcohol consumption and general and specific mortality in the Serbian
Methods. Total of 286 healthy middle-aged participants of both genders enrolled in a prospective follow-up study in
The relative risks (RR) adjusted for gender, smoking, body mass index, and blood pressure were calculated using
non-drinkers as a reference category.
Results. Heavy drinkers exhibited significantly higher adjusted ratios for all-cause mortality (RR=1.970, 95% confi-
level. Further, overall probability of survival at every time point was the highest among moderate drinkers and lowest
among heavy drinkers.
Conclusion. Among Serbian middle-aged population moderate alcohol consumption reduced mortality from all
ity in comparison with non-drinkers.
Key words: alcohol drinking; cerebrovascular accident; follow-up studies; mortality; myocardial infarction; survival
Many studies investigated the effects of alcohol
consumption on mortality (1). The relation with all-
cause mortality is usually reported as U- or J-shaped,
with moderate consumers having the lowest risk of
mortality and high consumersthe highest (2-4). How-
ever, there may be problems with the selection of the
non-drinkers group, since sick people may not drink
because of their illness, leading to an apparent in-
creased risk of mortality among them (5). Moderate
consumption of alcohol may protect against coronary
heart disease, but whether this is true for all types of
alcohol or just for wine is unclear (6,7).
The aim of the study was to establish the relation
between alcohol consumption and general and spe-
cific mortality during the follow-up period.
Participants and Methods
We performed a twenty-year prospective follow-up study of
healthy middle-aged participants who reported their alcohol con-
sumption, with detailed information on risk factors which might
act as confounders, including smoking, body mass index, and
There were 500 subjects aged 30-60 years, assessed for eli-
gibility at the Institute for Chronic Diseases and Gerontology –
Center for Hypertension, Belgrade, Serbia and Montenegro in
1974 (Fig. 1). After a detailed clinical examination, 65 subjects
were excluded from the study due to the presence of chronic dis-
eases (n=48) or a refusal to participate (n=17). Twenty years
later (1994) the investigation was repeated in the Center for
Blood Pressure Disorders, Institute for Cardiovascular Diseases of
the Clinical Center of Serbia, Belgrade. During the follow-up 130
patients were lost (n=36) out of 435 subjects enrolled either due
to loss of contact or quitting of the study (94). After analyzing the
data on 305 patients at the end of the follow-up period, we ex-
cluded 19 subjects due to insufficient information. The final anal-
ysis included 286 participants, 145 men and 141 women, who
enrolled in the study in 1974. During the follow-up, 80 persons
died. The information about the underlying cause of death (all
causes, myocardial infarction, stroke and other causes) were ob-
tainedfrom official death certificates.
Anthropometric parameters and arterial pressure were mea-
sured at the outpatient clinic, usually in the early morning. Body
weight was measured in underwear and body height without
shoes, and from these the body mass index was calculated
(weight [kg]/height2[m2]). Blood pressure (mmHg) was measured
at the end of the physician’s examination, with the participant ly-
ing down, and the average of 3 consecutive measurements was
All participants filled in a self-administered questionnaire
concerning general characteristics: age, marital status, education,
personal and family history of cardiovascular diseases, and vari-
oushealth related issues,including drinking and smoking habits.
Considering smoking habits, the subjects reported if they
had never smoked or were former or current smokers; the latter
two groups were united for the further analysis due to low num-
ber of former smokers.
Participants were asked in the multiple-choice format to de-
scribe their intake of alcoholic drinks, separately for each bever-
age type (beer, wine, and spirits). The choices were hardly
ever/never, monthly, weekly, or daily. One standard drink is gen-
erally considered to be 1 bottled beer (350 ml), 1 glass of wine
(150 ml), or 1 measure (40 ml) of distilled spirits. Each of these
drinks contains roughly the same amount of absolute alcohol –
10 to 12 grams (8). According to the guidelines from the National
Institute on Alcohol Abuse and Alcoholism, Bethesda, USA,
moderate drinking is defined as no more than 1 drink a day for
women (not pregnant), and no more than 2 drinks a day for men
(8). The subjects were then classified into 3 groups according to
the total daily intake of alcohol: rarely or never (less than 1 bever-
age a day), moderate drinking (1-2 beverages a day), and heavy
drinking (more than 2 drinks a day). The comparison of distribu-
tion according to drinking habits among the participants who sur-
vived showed that84% ofthem stayed in the same category ofal-
cohol consumption at the end of the study. That is why we hy-
pothesized that changes in drinking habits did not affect the reli-
ability of statistical reasoning for the whole sample.
Descriptive statistics were presented as mean values ±
standard deviation (SD) for numeric variables, or as percents (rel-
ative numbers) for categorical variables.
Differences in the age at the beginning of the study, body
mass index, and systolic and diastolic blood pressure between
groups were compared with parametric one-way analysis of vari-
ance (ANOVA) and least significant differences (LSD) post hoc
test for multiple comparisons, because these data had normal dis-
Differences between categorical data were tested by chi-
square test. Because we performed 15 consecutive statistical
analyses with chi-square test, we chose a level of significance of
0.003 – ?-adjustment according to modified Bonferroni proce-
dure for multiple comparisons.
Cox’s regression analysis was performed in order to calcu-
late adjusted relative risks for consumption and mortality from all
causes and from specific causes (myocardial infarction, stroke,
and other causes), using the nondrinkers as a reference category.
Relative risk was adjusted for gender, smoking habits, body mass
index, and blood pressure groups (according to the 7th Report of
the Joint National Committee on detection, evaluation, and treat-
ment of high blood pressure, ref. 9). Also, Kaplan-Meier method
was used for survival analysis.
Statistical analyses were performed using Statistica (Version
6; StatSoft, Inc., Tulsa, OK, USA).
With ? error of 0.05 and ? error of 0.20 (power 80%) and
this sample size, statistically significant difference in proportions
that could be identified equaled 0.2.
The majority of participants reported no or rare
ate and heavy alcohol consumption were reported by
a quarter of the respondents each (Table 1). The gen-
der distribution of the participants was similar: 145
(50.7%) men and 141 (49.3%) women. However,
men predominated in the group with heavy alcohol
consumption and women were the majority in the
other two groups (p<0.001). No statistically signifi-
cant differences were observed considering the aver-
age age of the participants at the beginning of the
There was significant correlation between alco-
hol consumption and smoking habits of the study
Jakovljeviæ et al: Alcohol Consumption and Mortality in SerbiaCroat Med J 2004;45:764-768
eligibility (n=500) 1974)(
Not meeting inclusion criteria (n=48)
Refused to participate (n=17)
Lost to follow-up (n=130)
Lost contact with participant (n=36)
Quitting the study (n=94)
Excluded from analysis due to insufficient data (n=19)
Final analysis (n=286) (1994)
Figure 1. Scheme of the study.
Table 1. Characteristics of study participants according to alcohol consumption at the beginning of the study 1974.
moderate (1-2 drinks/day)
No. (%) of participants
Age at the beginning of the study
Percent of men
Prevalence of smokers (%):
Body mass index (kg/m2)
Systolic blood pressure (mmHg)
Diastolic blood pressure (mmHg)
†Chi square test.
‡p?0.002 vs moderate, and p<0.001 vs heavy; chi-square test.
§p?0.001 vs heavy; chi square test.
llp?0.023 vs moderate; LSD post hoc test.
¶p=0.004 vs heavy; LSD post hoc test.
rarely or never
heavy (?3 drinks/day)
group. Less than a third of all smokers (including ex-
smokers) belonged to moderate drinkers, with the
tendency of increase among abstainers and heavy
drinkers (p<0.001). Statistically, most smokers be-
longed to the group of heavy drinkers, less to rare or
never drinkers, and the least percent to moderate
drinkers. The same pattern was observed for blood
pressure values: systolic pressure levels were the low-
est among moderate drinkers and increased in ab-
stainers and heavy drinkers; the differences between
moderate and non- or rare drinkers were highly statis-
tically significant (p=0.011) as well as differences be-
tween moderate and heavy drinkers (p=0.004). Dia-
stolic pressure levels were also lower among moder-
ate drinkers compared to the other two groups
(p=0.012).Moderate drinkershad significantly lower
diastolic blood pressure compared to non- or rare
drinkers (p=0.023), or heavy drinkers (p=0.004).
The three groups had similar values of body mass in-
dex at the beginning of the study (p=0.056).
A total of 80 deaths were registered during the
twenty-year follow up; 42 of these were attributable
to myocardial infarction, 7 to stroke, and 31 to other
causes of death (Table 2). The average age at the time
of death was 60.9±6.8 years and similar in all 3
groups of alcohol consumption. Considering death
from all causes, myocardial infarction and other
causes, the lowest fraction of participants who died
were moderate drinkers, with important increase
among abstainers and heavy-drinking participants –
the differences reaching high statistical significance
for general mortality and myocardial mortality
(p=0.016). Similarly, the lowest number of partici-
pants who died from stroke included moderate drink-
ers, whereas all others were abstainers, showing no
statistical difference between the groups (p=0.372).
Between-group comparisons revealed highly sig-
nificant differences between moderate and heavy
drinkers considering death from all causes, myocar-
dial infarction and death from other causes. The fre-
quency of death from all causes and myocardial in-
farction was significantly higher among heavy drink-
ers compared to rare or non-drinkers.
Moderate drinkers exhibited the lowest crude
mortality rates for death from all causes, myocardial
infarction, stroke and death from other causes (Table
ity rates for all-cause mortality, myocardial infarction
and death from other causes. Abstainers or those who
rarely drank had the highest mortality rate for stroke
compared to moderate alcohol consumption cate-
Moderate drinkers exhibited two times lower ad-
justed ratios for total mortality, myocardial infarction,
and death from other causes (Table 4). The risk for
stroke was nearly the same as for non-drinkers, which
can be explained by a small number of deaths from
this specific cause. Heavy drinkers exhibited signifi-
cantly higher adjusted ratios compared to non-drink-
ers for all causes of mortality except stroke. The ad-
justed ratios reached statistical significance for death
from all causes (p=0.031) and myocardial infarction
(p=0.038). Compared with abstainers, the average
risk of all cause of death among heavy pattern drink-
ers was increased up to three times; risk from myocar-
dial infarction death was increased up to five times,
whereas risk of death from other causes was in-
creased up to six times, when adjusted for gender,
smoking, body mass index, and blood pressure.
Kaplan-Meier model was used for the estimation
of the overall survival rates among the 3 groups of al-
cohol consumption (Fig. 2). The overall probability of
survival at any time point was the highest among
moderate drinkers, the lowest among heavy drinkers,
and the survival rate for non- or rare drinkers was
somewhere in the middle between the other two
groups (p<0.001). Between-group comparisons re-
vealed that the survival rate was significantly higher
among rare or never drinkers compared to heavy
Jakovljeviæ et al: Alcohol Consumption and Mortality in Serbia Croat Med J 2004;45:764-768
Table 2. Distribution of death events (No., %) in the 1974-1994 period according to alcohol consumption in 1974
Cause of deathrarely or never (n=140)
All causes36 (25.7)†
Myocardial infarction 15 (10.7)‡
Stroke 5 (3.6)
Other causes 16 (11.4)
*Chi square test.
†p=0.003 vs heavy; chi square test.
‡p<0.001 vs heavy; chi square test.
§p=0.019 vs heavy; chi square test.
7 ( 2.4)
Table 3. Mortality rate (per 1,000 person/years) for death
from all causes, myocardial infarction, stroke and death from
other causes in relation to alcohol consumption
rarely or never
Cause of death
Table 4. Relative risks (95% confidence intervals, CI) ad-
justed for gender, smoking, body mass index, and blood pre-
ssure of total mortality, myocardial infarction, stroke and
Relative risk (95%CI)†
of death rarelyornever*moderate
All causes10.533 (0.258-1.102) 1.970‡(1.062-3.651)
Stroke1 1.138 (0.207-6.268)
Other causes10.418 (0.118-1.481) 2.488 (0.863-7.177)
†Cox’s regression analysis.
§Statistical analysis was not conducted due to lack of death cases.
1 0.515 (0.180-1.473) 2.463‡(1.050-5.775)
drinkers (p<0.001), as well as among moderate
drinkers compared to heavy drinkers (p<0.001).
In this 20-year follow-up study, we found evi-
dence of potentially important protective as well as
hazardous effects of different drinking patterns on
health. First, it showed that a half of the studied popu-
lation, consisting mainly of women, abstained from
alcohol or rarely consumes alcohol beverages. Most
of the male participants, on the other hand, con-
sumed alcohol drinks every day in different amounts.
At the initial phase of the investigation, all groups
were overweight (10). Previous studies have showed
that being overweight might be an independent risk
factor for hypertension and heart failure (11,12). The
average values of both systolic and diastolic pressure
were indicative of prehypertension, according to the
7th Report of the Joint National Committee on Detec-
tion, Evaluation, and Treatment of High Blood Pres-
sure (9). The correlation between smoking and alco-
hol consumption was expected (13), but smoking
habits probably did not change the specific relation
of U- or J-shaped relationship between alcohol con-
sumption and total mortality rate (2-4,15-20), death
from cardiovascular diseases (2,14,21-23), stroke
(2,24), and death from other causes (4).
Possible biological mechanisms include an in-
crease in high density lipoprotein cholesterol, a de-
crease in platelet coagulability, and a decrease in
plasma fibrinogen associated with alcohol intake
Several limitations of this study should be con-
sidered. In particular, the small number of partici-
pants and their relatively young age at the beginning
of the study could have masked some of the possible
long-term health hazards of alcohol consumption, es-
pecially in older men and women. In addition, we
were unable to exclude former drinkers from the
non-drinking category. This could have resulted in an
increased mortality rate in the nondrinkers group;
however, we were able to eliminate participants with
prevalent cardiovascular disease.
The validity of self reported alcohol consump-
tion as a measure of consumption during the follow
include underreportingof alcohol consumption prob-
ably because people tend to forget light drinking oc-
a time over thepast 12 months, which is likely to give
a goodestimate onthelongterm drinkingpattern,it is
possible that some subjects later changed their drink-
ing pattern. Such changes are likely to dilute the ob-
served associationcomparedwith the actual one. The
problem of standard drink dose and the definition of
“moderate drinking” should be standardized in order
to avoid misunderstandings and allow precise com-
parisons between various populations.
The control for confounding factors included ad-
justments for smoking, body mass index, and blood
pressure, but they did not influencethe risk estimates.
The limitation of this study was that we did not con-
trol for diabetes mellitus as a confounding factor for
mortality. We also excluded cases with previous car-
diovascular diseases reported at the baseline exami-
nation, because they might have changed their drink-
ing patterns after the onset of the disease. Drinking
patterns can be influenced by and correlated to many
other factors: general health status, dietary habits,
physical activity level, and general tendency to
healthy or unhealthy behavior, but we were not able
to control all these possible confounders at this mo-
Public health implications of alcohol consump-
tion are of great importance. According to the World
Health Organization reports Serbia and Montenegro
is ranked in the lower 50th percentile among Euro-
pean countries in transition with regard to alcohol
consumption per capita (average=7.3 liters per ca-
pita per year). The average consumption did not sig-
nificantly change in the last decade of the 20th cen-
ing countries, such as Romania, Bulgaria, and Bosnia
and Herzegovina, with the exception of Croatia,
much higher (1,28).
The results of this twenty-year follow-up study
confirm the U- or J-shaped relation between alcohol
consumption and mortality from all causes, myocar-
dial infarction and other causes and support recom-
mendations for moderate alcohol consumption (one
to two drinks a day) in general population. Heavy
drinking significantly increased the risk for all-causes
mortality and the mortality from myocardial infarction
compared to non-drinking and moderate drinking.
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Received: April 9, 2004
Accepted: October 12, 2004
Institute for Hygiene and Medical Ecology
Belgrade University School of Medicine
Dr Subotiæa 8
11000 Belgrade, Serbia and Montenegro
Jakovljeviæ et al: Alcohol Consumption and Mortality in Serbia Croat Med J 2004;45:764-768