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IJE Advance Access originally published online on April 15, 2005
International Journal of Epidemiology 2005 34(4):781-788; doi:10.1093/ije/dyi078
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Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2005; all rights reserved.

Article

Alcohol consumption and its relation to risk factors for cardiovascular disease in the north-west of Russia: the Arkhangelsk study

Odd Nilssen1,*, Maria Averina1, Tormod Brenn1, Jan Brox2, Alexei Kalinin3 and Vadim Archipovski4

1 Institute of Community Medicine, University of Tromsö, Norway
2 University Teaching Hospital, Tromsö, Norway
3 Northern State Medical University, Arkhangelsk, Russia
4 Semashko Outpatient Clinic, Arkhangelsk, Russia

* Corresponding author. Institute of Community Medicine, University of Tromsö, 9037 Tromsö, Norway. E-mail: Odd.Nilssen{at}ism.uit.no


   Abstract
Top
 Abstract
Materials and methods
 Results
 Discussion
 GGT
 AUDIT
 Conclusions
 References
 
Background To explore indicators and levels of alcohol consumption in a Russian population, and to elaborate these in relation to risk factors for cardiovascular disease.

Methods A total of 1963 men and 1734 women, aged 18–75 years, consecutively recruited at their compulsory annual medical check-up at the Semashko outpatient clinic, Arkhangelsk, participated in a cross-sectional health survey. The survey comprised a physical examination, a six-page questionnaire on health and lifestyle, and blood tests.

Results Gamma-glutamyltransferase (GGT) levels in both sexes were more than twice as high as found in comparable studies. Elevated GGT-levels were 4–5 times more frequent than found in Norwegian studies. Alcohol Use Disorder Identification Test (AUDIT) identified up to 75% of male workers and 47% of female workers as hazardous or harmful alcohol drinkers. The traditional risk factors for cardiovascular disease were significantly higher in subjects with a high level of GGT.

Conclusion The findings indicate an extremely high level of alcohol consumption in this population. Elevation in GGT was significantly associated with increased risk for cardiovascular disease.

Keywords Alcohol, audit, gamma-glutamyltransferase, cardiovascular disease

Accepted 14 March 2005

Public health in Russia appears to have undergone a dramatic change for the worse since the collapse of the Soviet Union.1 During the last decade, significant increases in cardiovascular disease (CVD), infectious disease, suicide, and fatal injuries have been observed.2 In contrast to west European countries CVD mortality has increased and continues to rise.3 The increase from 2002 to 2003 was 2.5% (Goskomstat of Russia; www.gks.ru). As a consequence, life expectancy has decreased sharply and is significantly lower than in other European countries,4 being 57 years in males and 70 years in females. Life expectancy in the northern regions of Russia was found to be even worse5 in the range of 52–57 years for men and 64–70 years for women (Arkhangelsk, Comi, Karel).

Against this background a Norwegian–Russian cross-sectional population study was carried out in Arkhangelsk, Russia, in 1999–2000. The results showed that traditional risk factors for CVD were lower than expected.6,7 Adjusted values for apolipoprotein-AI (APO-AI), high-density lipoprotein (HDL) and physical activity were significantly higher, whereas blood pressure, total cholesterol, low-density lipoprotein (LDL), APO-B, BMI and the Framingham Risk Scores8 were significantly lower than in comparable studies from Europe. Thus other factors need to be considered.

While some health professionals have underlined the importance of poverty and socioeconomic distress as the main reason for the setback in population health and increase in CVD mortality,9,10 others have called attention to the effect of the heavy alcohol consumption in Russia.11–15 For example, data from the Russian Central Statistic Agency (Goskomstat) shows that even if deaths from natural causes account for a large proportion of the increase in death rates, deaths caused by alcohol, may be the largest proportion of the increase seen during the last decade (Goskomstat of Russia; www.gks.ru). Such an inference must take into account that official figures for alcohol consumption in Russia are uncertain and figures for unregistered sources of alcohol are still more uncertain.15,16 However, it appears that after the abolition of the State alcohol monopoly in 1992, the Russian populace has become one of the world leaders in alcohol consumption.14,17–20 As alcohol consumption could be a decisive factor, both directly and indirectly, for the high mortality rate in Russia, this study was designed to more carefully evaluate this role.


   Materials and methods
Top
 Abstract
 Materials and methods
Results
 Discussion
 GGT
 AUDIT
 Conclusions
 References
 
Arkhangelsk is located near the White Sea in the north-west of Russia. In this region there are ~1.5 million inhabitants of whom 370 000 live in Arkhangelsk itself. The majority of the population are employed in fishery or fishery-related work, but woodworking, military, and public service also employ significant sections of the population.

No population register for Arkhangelsk town was available to us. To overcome this problem we established our study centre at one of the outpatient clinics in the town. As this clinic (like all the other clinics in Arkhangelsk) was responsible for a certain number of specific factories and places of work and for a certain area of the town (according to occupational and territorial principles), they also had a kind of overview of the subjects they were responsible for. Their patients were of two categories; those who were ill and needed to see a doctor and those employed people who had to go through a ‘compulsory annual medical examination’ because of the particular industry or sector they worked in. In accordance with the clinic's leadership we decided to focus on the last group. This group had no fixed appointment at the clinic, but could attend the clinic between 8 a.m. and 12 noon on certain weekdays. Once they reported at the clinic, they were consecutively informed about the project and asked to participate. All of them were told that the study was anonymous and that the data would not affect their working status. As we aimed to get at an approximately equal number of participants of each sex and age group, some of the work places were contacted at the end of the study and informed that their staff/employees could report for the annual examination within the coming weeks or months, thus allowing us to reach an approximately equal number in each group. These ‘invited’ subjects were not informed about our project until they attended the clinic. All the subjects who refused to participate were registered, and the reason for this was recorded. At the end of the study period <1% of those asked had refused to participate, mainly due to lack of time. The regional ethical committee, Tromsö, Norway approved the study protocol.

Altogether 3697 subjects, 1963 men and 1734 women, aged 18–70 years were examined. Height, weight, waist and hip measurements were recorded and body mass index (BMI) and waist-hip ratio were calculated. Blood pressure and heart rate were measured with an automatic device (Dinamap-R, Criticon, Tampa, Florida) and measured three times at intervals of two minutes on the right upper arm in a sitting position. Blood lipid determinations and the calculation of the Framingham risk scores are described elsewhere (6). Each participant completed a questionnaire on demographical data, previous and present diseases, familiar disease, education, dietary habits, physical activity, smoking, drug and alcohol use, quality of life together with mental and sleeping problems. When used in the analyses, education was categorized as 1; primary (primary and incomplete secondary), 2; secondary (complete secondary), 3; professional secondary; 4; higher (incomplete and complete higher education or university).

Venous non-fasting blood samples were collected from all participants. The serum samples were kept at 220°C and transported to Tromsö once a month in special freezing boxes with freezing elements. All laboratory analyses were done by the Department of Clinical Chemistry, University Teaching Hospital, Tromsö, Norway.

Information on alcohol use was obtained through the use of the Alcohol Use Disorder Identification Test (AUDIT). The AUDIT21 consists of 10 items on alcohol drinking and has a maximum score of 40. A score of ≥8 indicates hazardous or harmful alcohol consumption, whereas ≥13 scores are likely to reflect alcohol dependence. In addition, AUDIT consists of three sections; a score of ≥5 (≥4 in women) on the first three questions (section-1) indicates a hazardous drinking level, a score of ≥4 on questions 4–6 (section-2) suggests psychological or physical dependence, and a score of ≥4 on questions 7–10 (section-3) suggests significant alcohol problems. The participants were also asked about frequency of alcohol intake (beer, wine, strong wine and liquor, categorized as, 1; seldom or a few times per year, 2; once a month, 3; 2–4 times per month, 4; 2–3 times per week, 5; about daily) and average weekly intake of liquor, beer, and wine (in alcohol units, 1 AU {approx} 13.8 gram pure alcohol).

Gamma-glutamyltransferase (GGT) was measured in all participants and used as a biological marker for alcohol intake.22 The measurements of GGT were done using a standard enzymatic colorimetric test (Roche, Mannheim, Germany) and performed at 37°C according to recommendations from the International Federation of Clinical Chemistry.23 The rise of free 5-amino-2-nitrobenzoate, proportional with the GGT activity, was determined photometrically with a Hitachi 917. The coefficient of variation (CV) was <2.5% for a commercial control serum. Study data were analysed using the SAS software package.24


   Results
Top
 Abstract
 Materials and methods
 Results
Discussion
 GGT
 AUDIT
 Conclusions
 References
 
Mean age was 41.8 and 44.2 years for men and women, respectively. Among men 71.3% were married or lived with a partner, 56.5% had professional education, and 21% had education from university or high school. Corresponding figures for women were 58.4%, 41.5%, and 32.5%. Altogether 12.1% of men and 29.9% of women reported to be teetotallers.

Table 1 gives mean GGT-values with standard deviations and medians for all participants, and mean GGT, AUDIT scores, and weekly intake (in AU) for non-abstainers according to age groups and sex. On average, males displayed 65% higher GGT values than females did. Mean GGT was 43.8 U/litre in males and 28.3 U/litre in females and increased with age (except for the highest age groups in males). Highest AUDIT scores were found in the age group 30–39 years in both sexes. Overall means were 7.5 and 3.9 for males and females, respectively. Corresponding figures for average weekly alcohol intake were 8.6 AU and 3.3 AU.


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  		Table 1 Numbers, mean values with standard deviation (SD) and medians of GGT (U/L) for the total population, together with percentages non-abstainers, mean GGT, AUDIT (scores) and weekly alcohol intake (in AU) for non-abstainers

 
Highest mean GGT-level among males was found in the group of seamen (Table 2), but also employees (white collars), industrial workers, pensioners, and ‘others’ (private business and unemployed) showed mean GGT-values >40 U/litre. Industrial workers and ‘others’ scored highest on AUDIT and they also reported highest intake of alcohol. Among females, pensioners and industrial workers displayed highest GGT values, whereas ‘others’ reported highest alcohol intake and scored highest on AUDIT.


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  		Table 2 Means with standard deviation (SD) for age, GGT, alcohol intake per week (units) and AUDIT scores for non-abstainers (numbers and % non-abstainers) for different working groups and gender

 
Almost two-thirds of the male industrial workers who reported any intake of alcohol (non-abstainers) scored ≥8 on AUDIT (Table 3), and three-fourths scored ≥5 on section-1 on AUDIT (indicating hazardous or harmful alcohol consumption). Between one half and two-thirds of the employees and ‘others’ reported hazardous or harmful levels of alcohol consumption. The same three groups also showed the highest percentage of subjects with GGT-levels above 50 U/litre and an alcohol intake >14 AU per week. In general, females displayed lower figures than males even though almost 50% of female industrial workers, housewives, and ‘others’ revealed scores on AUDIT section-1 corresponding to harmful drinking.


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  		Table 3 Specific characteristics (in %) in non-abstainers (numbers and % non-abstainers) for different working groups and gender

 
Table 4 gives the percentages for some drinking characteristics according to educational levels. Among males, AUDIT section-1 (≥5 scores) identified 50% more hazardous or harmful drinkers than did the full AUDIT (≥8 scores), among females even 100% more. Both sexes with education from high school or university reported highest intake frequency, but they drank less alcohol each time. Intake above 6 drinks per occasion among males was most frequent for those with professional education (mainly seamen). They also showed highest weekly intake. In males, 52.3% consumed ≥6 AU/occasion at least monthly, and 31.1% at least weekly. Almost 55% reported intake of ≥5–6 units per occasion, and 40.3% ≥7–9 units, whereas 74.2% reported intake of any alcohol ≥2–4 times a month, and 16.4% at least 2–3 times a week (data not shown). The highest mean GGT scores were among males with the most years of education. Females at all educational levels displayed substantially lower figures for all variables compared with males.


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  		Table 4 Subjects (in %) in different categories for AUDIT and GGT, and mean weekly intake of alcohol according to levels of education

 
A cross-tabulation of weekly intake (AU) and mean GGT with the first three questions (Q1–Q3) in AUDIT (frequency and volume) is shown in Table 5. Both numbers of AU per week and GGT increased with higher categories for all three questions except for GGT in the highest categories on Q1 and Q3.


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  		Table 5 Weekly intake of alcohol (AU) with numbers and mean GGT according to questions on frequency and volume (AUDIT 1–3) in non-abstainers

 
In age adjusted multiple regression analyses of logarithmically transformed GGT intake of liquor was significantly associated with GGT for both sexes. Among males, also intake of table wine, beer and numbers of alcohol units per drinking occasion displayed significant associations with GGT; among females increasing intake of strong wine and increasing frequency of intake >6 AU per drinking occasion increased the GGT-levels significantly (data not shown).

Table 6 displays age adjusted, sex-specific comparisons of risk factors for CVD and the Framingham risk score between groups with ‘high’ and ‘low’ GGT values in ANOVA analysis. The group ‘high GGT-level’ displayed significantly higher values for all variables in both sexes (except for cigarette smoking in females and HDL cholesterol in both sexes). As the Framingham risk score is only calculated for subjects >30 years, the sex-specific numbers for this variable are reduced. The Framingham risk scores are not adjusted for age, as mean age was almost equal for males and females.


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  		Table 6 ANOVA analyses of low and high GGT with age-adjusted mean serum lipids and blood pressure (BP) and the Framingham risk score in non-abstainers

 

   Discussion
Top
 Abstract
 Materials and methods
 Results
 Discussion
GGT
 AUDIT
 Conclusions
 References
 
The study population
The study population differed slightly from the Arkhangelsk region population6,7 as both levels of employment and education were higher in the current study. This may be seen as a rural–urban difference with better opportunities for work and education in the city. Age, marital status, rates of pensioners, female students, employed females, and females out of work were almost similar in the two populations. Thus, with these exceptions, the study population was found fairly representative for the Arkhangelsk region population.25

Alcohol consumption and drinking pattern
A potential weakness in the study is a possible underreporting of alcohol consumption. Study indicators of alcohol consumption (AUDIT, GGT) reveal a relatively high intake of alcohol among the participants. Corresponding figures from self-reported intake (Table 1) were not consistent with these findings. This may be owing to study context; workers might be worried that revealing a high alcohol intake at the annual medical check-up would put them at risk of losing their jobs. Even though they were assured that their questionnaire responses were confidential, the participants could have reported defensively on this type of request. It could be argued that asking for ‘an average week's intake’ could cause recall bias, as infrequent heavy users are more prone to underreport their intake when this method is used.20 However, asking participants about one week's intake is one of the most commonly used methods, and gives better estimates for frequent drinkers.20 Another possible explanation may be found in the drinking pattern: binge drinking (≥80 g at least once a month) was found for 52.3% of males and for 17.3% of females. These figures are slightly higher than those found among males in Novosibirsk,14 but much higher than the figures found in a study from Russia, Czech, and Poland.19 The figures for females were considerable higher in our study. Average intake at each drinking occasion was between 65–80 g and 150 g for 54.2% of males (20.5% of females), and ~75% of males (55% of females) consumed any alcohol between 2–4 times a month and daily. At the same time ~55% of males reported an average intake of ≥5–6 drinks each time they drank, but self-reported weekly intake was only 10 AU per week. Both quantity and frequency indicate a pattern of binge drinking. The magnitude of reported weekly intake does not reflect the high rate of binge drinking or the frequency and volume of intake on the AUDIT questions. It is also considerably less (annual 5.2 litres pure alcohol/capita) than official statistics (13.3 litres/capita) would indicate for total consumption in Russia.16 When the group ‘others’ reported highest weekly intake of alcohol in both sexes (Table 2 and 3), the explanation may be found in the composition of the group; it contains the unemployed and the self-employed workers, none of which were subject to possible sanctions in case of evident misuse of alcohol. We therefore believe that the discrepancy between self-reported alcohol consumption and GGT/AUDIT is likely to be due to underreporting.


   GGT
Top
 Abstract
 Materials and methods
 Results
 Discussion
 GGT
AUDIT
 Conclusions
 References
 
One of the most striking features in this study was the high GGT-level (Table 1). Both sexes revealed a mean level up to 100% higher than found in comparable studies. In a prospective study from England26 mean level of GGT was 15.6 U/litre in a sample of 7613 middle-aged men, and in the Third Tromsö Study (1986–87, with 20 782 participants), mean GGT was 22.4 U/litre in men and 13.8 U/litre in women.27 In Tromsö altogether 3.7% of the examined population had elevated GGT-values (≥50 U/litre in men, ≥45 U/litre in women) compared with 16.8% in this study (i.e. 4–5 times higher). Age may represent a confounding factor at least for GGT levels. The observed increase in GGT for the highest age groups in women thus proved to be mainly an effect of increased age and BMI (data not shown). Other possible reasons for the elevated GGT-levels in this study were evaluated, but complicating factors, such as use of drugs, dietary habits, and medical diseases (especially of the hepatobiliary type), gave no support to explanations of this kind.

GGT is well known as a marker of alcohol intake. Thus, the associations between GGT and alcohol intake in linear regression analyses was not unexpected. Less known is GGT as an indicator of oxidative stress and inflammation.28 There is also evidence that high alcohol consumption directly and indirectly contributes to oxidative stress and inflammation, and that the pro-oxidative effect plays an important role for the increased cardiovascular risk in subjects with high alcohol intake.29 GGT is also considered an independent predictor for hypertension, diabetes, and stroke.26,30,31 With the extremely high—probably alcohol-mediated—GGT-level found in our population, it is tempting to suggest that alcohol may be a major contributor to the setback in public health in the region, especially regarding CVDs.


   AUDIT
Top
 Abstract
 Materials and methods
 Results
 Discussion
 GGT
 AUDIT
Conclusions
 References
 
An analysis of non-abstainers in different working groups (Table 2) revealed low coherence between AUDIT scores and GGT-levels on one hand, and separately reported alcohol intake for men in all groups except for students. Hazardous or harmful drinking is diagnosed when a subject scores ≥8 on the AUDIT, the same applies if a person drinks >40 g pure alcohol/day. Average AUDIT scores were close to 8 or above for all professional workers (i.e. industrial workers, employees, and seamen). Self-reported intake on the other hand, was only between 1 and 1.5 AU/day (corresponding to 14–21 g/day) and thus significantly below a hazardous drinking level.32 The entire AUDIT identified significantly fewer hazardous drinkers than did the section-1 in AUDIT. In a publication from Seattle33 the 3-items AUDIT (labelled ‘AUDIT-C’) was tested in a group of male problem drinkers (heavy drinking, active alcohol abuse, or dependence). They concluded that the 3-items (AUDIT section-1 or AUDIT-C) performed better in identifying problem drinkers than did the entire AUDIT. Using ≥5 as cut-off, they found that AUDIT-C displayed higher sensitivity but slightly lower specificity than the entire AUDIT. Even though we are unable to give estimates for sensitivity and specificity, our data confirm the differences in performance between the two instruments. Between two-thirds and three-quarters of active male workers (industrial workers, employees, seamen, and others) were identified as hazardous or harmful drinkers according to the criteria in AUDIT section-1, whereas only ~50% of the subjects in these groups were labelled as hazardous drinkers when the entire AUDIT were used (Table 3). The same differences were observed in women, but the absolute figures were smaller.

No substantial differences were seen in AUDIT, GGT, and weekly intake when these variables were analysed separately for the different educational levels, although both males and females with higher education displayed somewhat higher figures for intake frequency. On the other hand, they drank less each time, and few reported binge drinking (≥6 drinks at one occasion). Nevertheless, well-educated males had slightly higher mean GGT-level (not in females), which may indicate that drinking frequency is of importance for elevated GGT.

Alcohol drinking and CVD
As reported in a previous paper, the classical risk factors for CVD (except for smoking) were more favourable in our Russian sample than in comparable studies from Western Europe and USA.6 At the same time the rates for CVD deaths is higher than elsewhere, and is still increasing.3 This apparent paradox is not easy to explain. One hypothesis is that predispositions for CVD may result from exposure to poverty and malnutrition in childhood and adolescence (the Forsdahl/Barker-hypothesis), leaving subjects with increased vulnerability for CVD.34,35 Subjects with increased vulnerability and a total cholesterol level of e.g. 5 mmol/litre might therefore carry a higher risk for CVD than do the un-exposed with the same cholesterol level. The devastating situation in Russia in the interwar period, during the war, and in the post-war period, might therefore be more important for the increase in death rates seen in the last decades rather than the absolute level of the classical risk factors.

In a study from England Wannamethee et al.26 found that GGT was strongly associated with CVD, all causes mortality and with the risk factors for CVD. Also studies from Russia have pointed to alcohol consumption (especially heavy and binge drinking) as a risk factor for increased CVD mortality.14,15,36 Our study did not include variables to directly analyse the effect of alcohol on CVD mortality. We found high levels of problem drinkers and high levels of GGT, which were associated with risk factors for CVD (Table 5). On the other hand, the risk factors were in general low in our study population. A possible explanation is that alcohol may not be the cause of high CVD because of its effect on the risk factors alone, but may (in addition) have a direct effect on CVD. Further investigations are needed, and a follow-up based on information from a newly established disease- and death-registers for our study population is under way.


   Conclusions
Top
 Abstract
 Materials and methods
 Results
 Discussion
 GGT
 AUDIT
 Conclusions
References
 
Mean GGT level was extremely high in this population, and AUDIT section-1 indicated that up to 75% of the subjects in some working groups met the criteria for hazardous or harmful alcohol drinking. Classical risk factors for CVD were significantly more favourable in subjects with low GGT than in those with high GGT.


KEY MESSAGES

  • Altogether, 1963 males and 1734 females were examined in a health survey in Arkhangelsk in northwest Russia.
  • Mean levels of gamma-glutamyltransferase (GGT) were more than twice as high as those found in comparable western studies, and considerably higher than found in Russian studies.
  • Hazardous or harmful drinkers were between 4 and 5 times higher than in studies from Norway.
  • High GGT was significantly associated with risk factors for coronary heart disease.

 


   Acknowledgments
 
The study was funded by the Norwegian Research Council.


   References
Top
 Abstract
 Materials and methods
 Results
 Discussion
 GGT
 AUDIT
 Conclusions
 References
 
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