T he inverse relation between alcohol intake and ischaemic

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1 24 RESEARCH REPORT Tyes of alcoholic beverages and blood liids in a French oulation J-B Ruidavets, P Ducimetière, D Arveiler, P Amouyel, A Bingham, A Wagner, D Cottel, B Perret, J Ferrières... See end of article for authors affiliations... Corresondence: Dr J-B Ruidavets, INSERM U558, Déartement d éidémiologie, Faculté de médecine, 37, allées Jules Guesde, Toulouse cedex, France; ruidavet@cict.fr Acceted for ublication 13 June J Eidemiol Community Health 2002;56:24 28 Study objective: Prosective studies have shown a consistent relation between alcohol consumtion and decreasing incidence of coronary artery disease. The rotective effect of alcohol could be mediated through increased levels of HDL cholesterol (HDL-c). The aim of this study was to examine the relation between blood liid levels and the consumtion of different tyes of alcoholic beverages among 1581 men and 1535 women. Design: Data from reresentative cross sectional surveys ( ) in three different regions of France were used. The consumtion of the different tyes of alcohol was quantified using a recall method according to a tyical weekly consumtion. Main results: The median daily alcohol intake was 24 g for men and 4 g for women. After adjustment for confounders, total alcohol showed a ositive and significant association with HDL-c and triglycerides (TG) in both sexes. In multivariate analysis, wine was ositively associated with HDL-c. Beer was ositively associated with HDL-c in men and with triglycerides in men and women. When taking drinking atterns into account, wine drinkers had higher HDL-c levels than non-wine drinkers. Differences became non-significant after adjustment for confounders and articularly for socioeconomic arameters. Conclusions: In a French oulation samle, total alcohol was ositively associated with HDL-c and triglycerides. The secific influence of any articular alcoholic beverage on blood liids was not clearly demonstrated but wine reference found in a grou with higher lifestyle standards was associated with a more favourable blood liid rofile. T he inverse relation between alcohol intake and ischaemic heart disease is mediated by numerous otential biological mechanisms. A large art of the beneficial effects of alcohol and of the various tyes of beverages on ischaemic heart disease has been ascribed to the increase in HDL cholesterol. 1 4 Some authors have reorted that the beneficial effects of wine were greater than those of any other beverage, 56 but others have suggested that the beneficial effects of beer 7 9 or both beer and wine were more effective. 10 However, the secific influence of each tye of alcoholic beverage on HDL-c has been less investigated. The results of these studies do not show significant differences between the various tyes of beverages on HDL-c Nevertheless, no study has ever been carried out among oulations in which alcohol consumtion attern is a regular one with all tyes of alcoholic beverages being affordable and available and with wine being the common alcoholic drink. The relation between the various tyes of alcoholic beverages and ischaemic heart disease is confounded by social and cultural factors, lifestyle and diet. 15 The influence of these environmental factors in the relation between alcoholic beverages and blood liids was not investigated. The aim of this study is to assess the otential relation between the amount of alcohol intake, the tye of beverage and blood liids in a French oulation samle characterised by a regular alcohol drinking attern and where alcohol consumtion is sulied mainly by wine. METHODS Poulation samling A cross sectional study was carried out from December 1994 to Aril 1997 in three regions of France. A oulation samle of 1581 men and 1535 women aged from 35 to 64 years was selected at random, in the north (Lille 555 men/558 women), in the east (Strasbourg 472 men/473 women) and in the south west (Toulouse 554 men/504 women). The oulation samles were drawn from the olling lists available in each town hall. Particiants were volunteers. Subjects were informed of the aim of the study and a formal consent was comleted and signed by each subject. Authorisation from the aroriate ethics committee was obtained. Subjects were screened for cardiovascular risk factors in a health screening centre or at home. Alcohol consumtion Total alcohol consumtion and alcohol intake from each beverage tye were assessed by quantitative questionnaires administered by a secially trained nurse. Moreover, drinking atterns secifying time and lace of consumtion, tyes of beverage and alcohol addiction (CAGE questionnaire) were established. Drinking habits were evaluated for each day according to a tyical weekly alcohol consumtion. Each tye of alcoholic beverage (wine, beer, cider aeritifs and sirits) was recorded. Total alcohol was calculated as the sum of all the tyes of alcohol consumed and exressed in grams of alcohol er day. Clinical measurement Research nurses, secially trained in agreement with the MONICA rotocol, 16 erformed clinical measurements. Anthroometric measurements including height, body weight, waist and hi circumferences were taken in agreement with standardised rocedures. Body mass index (BMI) and waist to hi ratio (WHR) were comuted as follows: weight (kg)/height (m 2 ) and waist/hi resectively. Blood ressure was measured twice in a sitting osition, on the right arm with a standard mercury shygmomanometer after a five minute rest.... Abbreviations: HDL-c, HDL cholesterol

2 Tyes of alcohol and blood liids 25 Table 1 Alcohol consumtion (g/d) and clinical and socioeconomic arameters in men Measurements rounded to the nearest 2 mm Hg. The average of the two measurements was used for the statistical analysis. Questionnaire Questionnaires reorting demograhic and socioeconomic factors, educational level and years of schooling, occuational activity, revious medical history, smoking habits (including ast and resent behaviour and the number of cigarettes, ies or cigars smoked) drug intake and hysical activity were administered by interviewers at the health screening centre or at home. Blood samle collection and biological analysis A blood samle was collected after a minimum fasting eriod of 10 hours, ket in tubes at room temerature and centrifuged within three hours. Serum tubes were stored at 80 C temerature. All biological analyses were erformed in a central laboratory. Liid and liorotein arameters were analysed two weeks after the blood samle had been drawn. Glucose, triglycerides (TG) and total cholesterol were measured by enzymatic reagents, on an automated analyser (Dade-Behring, Les Ulis, France), as described in Marques- Vidal et al. 17 High density liorotein cholesterol (HDL-c) was assayed following a rior reciitation of AoB/AoE containing lioroteins with hoshotungstic acid and magnesium (Roche-Diagnostics, Meylan, France). Low density liorotein cholesterol (LDL-c) was calculated according to Friedewald et al. 18 Aoliorotein A-I (Ao A-I) and Aoliorotein B100 (AoB) were determined by first order immunoreciitation in an automated analyser (Cobas-Mira, Roche-Diagnostics). Statistical methods Statistical analyses were erformed using the SAS statistical software release A statistical analysis was conducted among men and women searately because the drinking atterns and the amount of alcohol intake were very different. The statistical significance of the difference between the grous was tested by the χ 2 test for categorical variables and by one way analysis of variance for continuous ones. For variables with skewed distribution, analysis was erformed after logarithmic transformation. The influence of the tye of alcohol on liid and liorotein arameters was analysed with a multivariate 0 n= n= n= n=388 >80 n=107 mean SD* mean SD mean SD mean SD mean SD Alcohol consumtion (g/d) Beverages (% from total alcohol) wine beer aeritifs sirits Age (y) <0.001 Years of schooling (y) <0.001 Systolic ressure (mm Hg) <0.001 Diastolic ressure (mm Hg) <0.001 Waist to hi ratio <0.001 Body mass index (kg/m 2 ) NS Fasting glucose (mmol/l) <0.01 Centre (%) <0.001 North East South Current smoker (%) <0.001 Physical activity (%) <0.01 Drugs (%) antihyertensive <0.001 hyoliidaemic NS antidiabetic NS Occuational activity (%) <0.001 *Standard deviation; intense hysical activity, 20 min, three times a week or more. linear model after adjustment for confounding variables. The heterogeneity of adjusted β estimators was tested using the F test. An ANCOVA statistical analysis was erformed (abstainers were excluded) to comare the mean values of blood concentrations of liids, lioroteins and aolioroteins between the different grous (subjects who consumed wine only, alcohol beverages other than wine, wine and other alcohol beverages) after adjustment for confounding factors. RESULTS In this oulation samle, 36.7% of women and 15.4% of men reorted that they drank no alcohol at all. Conversely 6.8% of men consumed at least 80 g alcohol a day and 31.3% of men drank 40 g or more er day. In women, only 4% consumed 40 g alcohol or more er day. For men, wine accounted for 66.2%, beer 16.8% and aeritifs 13.2% of total alcohol. For women, wine accounted for 63.7%, beer 6.8% and aeritifs 18.4% of total alcohol. Table 1 shows the main characteristics of men in relation to their total alcohol intake. The ercentage of beer increased with the amount of total alcohol intake and the ercentage of aeritifs was twice higher in the light drinkers than in the other grous of alcohol drinkers. Men, who were heavy drinkers, were older than abstainers and they were more revalent in the north than in the east and in the south. The number of years sent in school was on average higher among subjects with light alcohol consumtion or abstainers. Mean levels of systolic and diastolic blood ressures, waist to hi ratio and fasting blood glucose increased significantly with alcohol consumtion. The amount of total alcohol intake was ositively associated with the ercentage of current smokers and inversely correlated with the ercentage of men who had intense hysical activity. An increase in the roortion of men taking antihyertensive drugs was associated with a rise of alcohol intake. In the same way, the roortion of heavy drinkers in women was higher in the north than in the east and in the south (table 2). We found significant differences related to alcohol intake, for body mass index, waist to hi ratio, fasting glucose and hysical activity. In men, after adjustment for confounding variables, mean blood levels for HDL-c, triglycerides and Ao A-I increased

3 26 Ruidavets, Ducimetière, Arveiler, et al Table 2 Alcohol consumtion (g/d) and clinical and socioeconomical arameters in women significantly in relation with the rank of each grou of total alcohol consumtion. In women, for HDL-c and Ao A-I identical results were obtained and for triglycerides, highest blood concentrations were observed in abstainers and when alcohol consumtion was greater than 20 gaday(datanotshown). Table 3 shows the relations between the tye of alcohol and the blood liid concentrations. Coefficients of multile linear model were adjusted for antihyertensive, antidiabetic and hyoliidaemic drugs, for centre, age, body mass index, smoking habits, systolic blood ressure, years of schooling, fasting blood glucose, hysical activity and occuational activity. In both sexes, total cholesterol and HDL-c were ositively associated with wine consumtion. HDL-c was ositively associated with beer in men and aeritif consumtion in women. In both sexes a ositive association was observed between beer and triglycerides. When homogeneity of β coefficients of the linear regressions was tested, no significant differences were found 0 n= n=708 >20 n=264 mean SD* mean SD mean SD Alcohol consumtion (g/d) Beverages (% from total alcohol) wine beer aeritifs sirits Age (y) NS Years of schooling (y) NS Systolic ressure (mm Hg) NS Diastolic ressure (mm Hg) NS Waist to hi ratio <0.01 Body mass index (kg/m 2 ) <0.001 Fasting glucose (mmol/l) <0.05 Centre (%) <0.001 North East South Current smoker (%) NS Physical activity (%) <0.001 Drugs (%) antihyertensive NS hyoliidaemic NS antidiabetic NS Occuational activity (%) NS *Standard deviation; intense hysical activity, 20 min, three times a week or more. in men. In women, significant difference (<0.05) was noticed for HDL-c. Similar results were obtained for Ao A-I. Tables 4 give adjusted means of liid levels according to three atterns of alcohol intake : wine drinkers exclusively, a mixed attern (including wine or beer or aeritif or cider or sirits) and subjects who drank all tyes of alcohol, excet wine. This analysis was carried out after exclusion of abstainers. In men, only blood concentrations of triglycerides remained significantly different between the three grous (<0.01) after adjustment for total alcohol consumtion and several confounding factors. In women, after adjustment for confounders, no significant difference was observed for studied blood liids. DISCUSSION This cross sectional study shows a ositive association of HDL-c or Ao A-I with alcohol intake. This association seems to ut into evidence a continuous dose deendent relation in Table 3 Coefficients of linear regression of blood liids uon intake of tyes of alcohol Men n=1581 Women n=1535 β* SE F β SE F Total cholesterol 0.57 NS 1.47 NS Wine < <0.05 Beer NS NS Aeritif NS NS Sirits NS NS HDL cholesterol 1.54 NS 3.23 <0.05 Wine < <0.001 Beer < NS Aeritif NS <0.01 Sirits NS NS Triglycerides 2.48 NS 1.73 NS Wine NS NS Beer < <0.01 Aeritif NS NS Sirits < NS Adjusted for antihyertensive, antidiabetic, hyoliidaemic drugs, centre, age, smoking, systolic blood ressure, fasting blood glucose, years of schooling, hysical activity, body mass index and occuational activity. *β coefficient corresonding to an increase of 1 g of alcohol intake; significance of β coefficients; test of equality of β coefficients; significance of the test of equality.

4 Tyes of alcohol and blood liids 27 Table 4 Blood liids Drinking atterns and blood liid levels among drinkers Wine only both men and women. On the other hand, triglycerides increased when alcohol consumtion reached 40 g/day in men whereas, in women, no obvious trend was observed when total alcohol intake increased. The small ercentage of women consuming more than 40 g/day of alcohol (4%) could account for the different attern concerning the alcohol-triglycerides relation found in men. This graded resonse of HDL-c with alcohol consumtion and the rise of triglyceride with a daily alcohol intake of 40 g, has been reorted in a similar study carried out in a Jaanese oulation samle of men aged years. 20 The results of our reort are consistent with a majority of eidemiological studies describing a ositive relation between HDL-c and alcohol consumtion The relations between the tyes of beverages and blood liids were tested in a linear regression model and according to three atterns of alcoholic beverages. In the first aroach the results showed that HDL-c was associated ositively with wine and beer in men, and in women with wine and aeritif consumtion. For both sexes, these beverages reresented the highest roortion of alcohol intake. In men, wine and beer together reresented 86% of the total alcohol intake, and in women, wine and aeritifs reached 82%. Therefore, we can suggest that the association between alcohol and HDL-c (similar relation with Ao A-I) was influenced more by the amount of alcohol in the different tyes of beverages than by the tyes of beverages in themselves. The secific influence of a given alcoholic beverage on HDL-c seems rather hyothetical. In any case, the demonstrated influence of alcoholic beverages on HDL-c results from the secific role of ethanol. The otential additive effect of wine 59 against ischaemic heart diseases, or of beer 78 or of any tye of alcoholic beverages 9 is robably not mediated by HDL-c metabolism. On the other hand, we found a ositive association between beer and triglycerides in men and in women. It seems that the quantity of alcohol alone cannot account for this relation, as the roortion of alcohol sulied by beer, when comared with other beverages was low in women and just a little higher in men than in women. In the second aroach, considering wine comared with non-wine consumtion, we tried to assess whether blood liids were associated with drinking atterns. After adjustment for total alcohol intake, centre and hyoliidaemic drugs, the results showed that the HDL-c levels were significantly higher for wine consumers versus non-wine consumers. When adjustment was erformed for other covariates, differences between drinking atterns were reduced and the relation became non-significant. The finding was consistent for men and women. In contrast, after adjustment for the same arameters, triglyceride level in men remained significantly Other beverages* Wine+other beverages mean SE mean SE mean SE Men n=203 n=103 n=1031 HDL cholesterol (mmol/l) A <0.05 B NS Triglycerides (mmol/l) A <0.01 B <0.01 Women n=241 n=124 n=607 HDL cholesterol (mmol/l) A <0.05 B NS Triglycerides (mmol/l) A NS B NS *All tyes of beverages excet wine; all tyes of beverages; adjusted for hyoliidaemic drugs, centre and total alcohol consumtion; adjusted for antihyertensive, antidiabetic, hyoliidaemic drugs, centre, age, waist to hi ratio, smoking, systolic blood ressure, years of schooling, hysical activity and total alcohol consumtion; erformed after log transformation. higher in non-wine drinkers desite attenuated differences between the three grous. In women, the lack of relation between triglycerides and drinking atterns was in agreement with the low amount of total alcohol intake. Thus, the relations between the different tyes of beverages and HDL-c or Ao A-I could be largely exlained by standard of living, sociocultural factors and the balance between the amount of the different tyes of alcohol intake and the reference beverage. Globally in this study, the amount of total alcohol intake was ositively associated with age, tobacco consumtion, body mass index, waist to hi ratio, and negatively with years of schooling. When considering the different tyes of alcoholic beverages, it has been shown that in oulations where wine is not the main alcoholic beverage, wine drinkers had a healthier lifestyle and a lower risk factor rofile when comared with other drinkers It was shown that moderate consumtion of wine was associated with good subjective health also. 31 In this study similar traits were found in wine drinkers. Body mass index was lower and the roortion of alcohol sulied by wine was higher in the subjects who had hysical activities and a higher educational level. By contrast, beer drinkers were associated with a higher roortion of current smokers, a higher roortion of men, a lesser hysical activity and a higher waist to hi ratio. The area of residence was also one of the main determining factors for the choice of alcoholic beverage as it was reorted 10 years ago. 32 Beer was mainly consumed in the north of France and wine in the south whatever the sex. In this study, beer reresented 31% and wine 56% of total alcohol intake for men living in the north. By contrast, in the south, wine accounted for 87% and beer 5% of total alcohol intake. A similar attern was found for women. Aeritifs were consumed mainly in the north and sirits in the east of France. In France, wine is the most common and the most oular alcoholic beverage. Its wide range of rices makes it affordable whatever the socioeconomic status of the oulation. In this oulation samle, among alcohol consumers, the roortion of eole who did not consume wine was very low, 7.7% and 12.7% of men and women resectively. Even among the mixed consumtion attern, wine was reonderant and reresented 66% of total alcohol intake. Therefore, we can assume that familial, social and cultural environments influence the choice of alcoholic beverages. These results suggest that lifestyle standards connected with wine reference are associated with a better blood liid rofile. Furthermore, one of the main factors influencing blood liids that is not taken into account in this study is the diet. A recent ublication concerning a survey carried out in

5 28 Ruidavets, Ducimetière, Arveiler, et al Key oints Total alcohol consumtion is ositively associated with high density liorotein and triglycerides. The influence of any secific alcoholic beverage on blood liids is not demonstrated. A more favourable blood liid rofile is observed among wine consumers with the highest lifestyle standards. Denmark reorted that wine drinking was associated with a higher intake of fruit, vegetables and olive oil for cooking. 15 Nutritional habits and cardiovascular risk factors were investigated comaring a French oulation with a Northern Irish oulation. The conclusion was identical: wine drinkers had a healthier dietary attern than other alcoholic beverage consumers. 33 Moreover, a ossible bias related to misreorted alcohol intake leading to misclassified subjects was considered by comaring reorted alcohol consumtion with γ-glutamyltransferase, mean coruscular volume and CAGE questionnaire. The comarison of mean values of alcohol consumtion across the ordered grous of γ-glutamyltransferase, mean coruscular volume and the CAGE questionnaire showed a significant graded relation (data not shown). The same analyses were then erformed for HDL-c, Ao A-I and triglycerides. The results showed that the relations found with these markers were consistent with the findings in the alcohol grous. These relations when comared to the alcohol questionnaire were more consistent with mean coruscular volume for HDL-c and Ao A-I and with γ-glutamyltransferase and the CAGE questionnaire for triglycerides. CONCLUSION In a French oulation samle, total alcohol intake was ositively correlated with HDL-c, Ao A-I and triglycerides in both men and women. A secific influence on liids by a given alcoholic beverage was not demonstrated clearly. However, nutritional habits, lower cardiovascular risk and higher social status linked to a wine consumtion attern could induce a more favourable blood liid rofile. In contrast, high alcohol intake is associated with high blood ressure, high waist hi ratio, the rise of triglyceride levels and unfavourable lifestyle behaviours such as smoking habits and low hysical activity. ACKNOWLEDGEMENTS Funding: this study was suorted by grants from the Institut National de la Santé et de la Recherche Médicale INSERM, the Direction Générale de la Santé, the Fonds d intervention en Santé Publique, the Mutuelle Générale de l Education Nationale, the Fondation de France, the CPAM de Sélestat, the Association régionale de Cardiologie d Alsace, the Conseil Régional du Nord-Pas de Calais, the Institut Pasteur de Lille, the Unité d évaluation du CHU de Lille and the Laboratoires Parke-Davis. Conflicts of interest: none.... 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