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Lack of association between dietary alcohol and HDL-cholesterol concentrations in obese women
Atherosclerosis, 81 (1990) 119-125 Elsevier Scientific Publishers Ireland,
ATHERO
119 Ltd.
04436
Lack of association between dietary alcohol and HDL-cholesterol concentrations in obese women Jacques Fricker,
Fr&dQic Fumeron, Samira Chabchoub, and Anik Girard-Globa
INSERM
Marian Apfelbaum
U. 286, Human Nutrition, Medical School X. Bichat, Paris (France) (Received 16 June, 1989) (Revised, received 21 November, 1989) (Accepted 23 November, 1989)
Summary
The relationships of alcohol intake and corpulence to HDL-cholesterol were studied in 653 women taking medical advice about body weight. The body mass index (BMI) was positively correlated with triglyceride and negatively with HDL-cholesterol. The relation between BMI and HDL-cholesterol was discontinuous. Total cholesterol, triglycerides and diastolic blood pressure were increased for alcohol intakes greater than 10 g/d regardless of body weight. Alcohol intake was associated with higher concentrations of HDL-cholesterol (P = 0.006) in non obese (BMI = 25.2 f 1.5 kg/m*) subjects, but not in mildly (27.3 < BMI < 32.3) or massively (BMI >, 32.3) obese subjects. The fact that HDL concentrations were not associated with alcohol intake in obese patients suggests that (1) alcohol acts on the HDL pool through one of the pathways which are perturbed in obesity, possibly lipolysis, (2) obesity is one of the reasons for the differences in individual responses of HDL-cholesterol to alcohol, (3) myocardial infarction might not be inversely correlated with alcohol intake in the obese as it is in the non-obese population.
Key words:
Alcohol;
Cholesterol;
High density
lipoprotein;
Introduction
A moderate level of alcohol intake has repeatedly been found to be associated with a decreased incidence of coronary heart disease (CHD) [l-3]. Alcohol is also reported to increase con-
Correspondence to: Dr. Jacques Fricker, INSERM Human Nutrition, Medical School Hapital X. Bichat, Henri Huchard, F-75018 Paris, France. 0021-9150/90/$03.50
0 1990 Elsevier Scientific
U.286, 16 rue
Publishers
Ireland,
Obesity;
Triglyceride
centrations of high density lipoprotein (HDL)cholesterol [4-61. Since a negative relationship exists between HDL-cholesterol and the incidence of CHD [7,8], it has been postulated that the negative association of alcohol intake with CHD might be partly mediated by the increase of HDL. The data are, however, suggestive of differences in individual responses of HDL-cholesterol to alcohol. Epidemiological studies demonstrate that obesity is on the contrary associated with an increased risk of coronary heart disease [9,10]. Ltd.
120 Although obesity per se might be an independent risk factor [ll], the relationship could also be mediated by its association with other cardiovascular risk factors, such as hypertension, non insulin-dependent diabetes and lipoprotein abnormalities [9,12]; increased concentrations of serum very low density lipoproteins (VLDL) have frequently been reported in obese [13,14], as well as a reduction of HDL-cholesterol, occurring even in normotriglyceridemic subjects [9,12,15,16]. The present work was designed to determine if, amongst an overweight population, alcohol does increase HDL-cholesterol despite the alteration in HDL metabolism due to obesity, or whether the factors underlying obesity are one of the reasons for the differences in individual responses of HDL-cholesterol to alcohol. Methods Subjects The study was carried out on 653 women seeking medical advice about body weight in the Nutrition Clinic of Bichat Hospital. Body weight was measured without shoes or clothes to the nearest 0.1 kg. Height was also measured without shoes to the nearest 1 cm. The body mass index (BMI; kg/m2) was used to assess corpulence. In the months before the study all subjects had been on spontaneous diet. None received medications that might affect their lipid levels. Most were sedentary (less than 1 h physical exercise per day). Although all subjects consulted the weight control unit because of a concern about body weight, some were not obese but only moderately overweight. Following the guidelines of the National Health and Nutrition Examination Surveys, 1976-80 (NHANES II) [17], the women were distributed into 3 groups: 226 non-obese (BMI < 27.3), 233 mildly obese (27.3 G BMI < 32.3), and 194 severely obese (BMI > 32.3). Supine systolic and diastolic blood pressures were measured at the study-site after a 5-min rest. Food intake Intake was assessed by use of a dietary history questionnaire covering a period of 1 month. 450 questions cover successively, breakfast, lunch, dinner, snacks and nibbling. For lunch and dinner, an
alternative is proposed: “cooked” or “uncooked”, which reflects the tendency for a difference between formal meals versus sandwiches or fast food. For the formal meals, traditional phases (starter, main dish, cheese, dessert, bread, drinks) are proposed. Specific questions are designed to cover alcohol intake over 24 h, distinguishing between coktail-time drinks, meal-time, after-meal, between-meals and nocturnal drinks. For each period a large choice of usual items are suggested. The subject answers in terms of weekly frequency for the meal, the phase, the food or the drink. Foods consumed very occasionally can be recorded with a frequency smaller than one. The amounts of alcohol are estimated through independent but overlapping questions regarding the size of glasses, the level of filling and number of refills and the number of bottles drunk a week. Calibrated glasses help the subject to better estimate amounts. The filled questionnaire was reviewed by a dietitian together with the patient, and cross-checked for reliability and coherence of the information on amounts and frequencies. The nutritional data were computerized using a compilation of 2 food tables [19,20]. The stated purpose of these enquiries was to prescribe a personalized diet fitting the patient’s habits. Neither the dietician, nor the patient were aware of the epidemiological aspect of these enquiries, in order to attenuate the observer effect linked to dietary epidemiological studies. The efficiency of this questionnaire had been assessed elsewhere against estimated total energy expenditure [18]. Lipid, lipoprotein and apoprotein measurements Blood samples were collected after an overnight fast. Serum cholesterol and triglycerides were assayed using commercial test kits (Biotrol, Lyon, France). VLDL were prepared by ultracentrifugation: 2 ml serum were diluted with 1 ml 0.9% NaCl and centrifuged for 3 h (10 o C) in a Kontron TFT 45,6 rotor at 45000 rpm. Cholesterol was determined in VLDL and infranatant by the same methods as in the serum. LDL in infranatant were precipitated by phosphotungstate-MgCl 2 and cholesterol assayed in the supernatant considered as the HDL fraction [21]. LDL cholesterol was determined by substraction. Serum apoproteins (apo A-I and B) concentrations were determined
121 by the Laurel1 France).
method
(“Apofilm”
Sebia,
TABLE 1
Issy,
CORRELATION COEFFICIENTS OF SELECTED RISK FACTORS WITH AGE AND BMI
Stutistics Statistical analysis was performed using the MGLH module of the Systat program [22]. Relationships between continuous variables were assessed by the correlation coefficients. Means were compared by analysis of variance or analysis of covariance after inclusion of age in the model. A multiple regression analysis was performed with HDL cholesterol as the dependent variable and corpulence status, alcohol intake, age and the interaction term between alcohol consumption and corpulence as independent predictors. Since the interaction between obesity and alcohol intake was found to be significant, a model including alcohol and age was tested in each class of corpulence. Triglyceride values were tested after log transformation.
BMI
Age Cholesterol LDL-cholesterol HDL-cholesterol Triglycerides Systolic blood pressure Diastolic blood pressure Apo B Apo A-I HDL-C/APO A-I ** ***
0.53 0.45 0.14 0.27
CHD
*** *** *** ***
0.11 0.14 -0.19 0.31
** *** *** ***
0.44 * * *
0.29 * * *
0.35 * * * 0.38 * * * 0.19 *** ns
0.26 *** 0.18 * * * ns -0.18
***
P
and each selected risk factor, except total cholesterol. Apo A-I was not correlated with corpulence; this resulted in a negative relationship between BMI and the ratio of HDL-cholesterol to apo A-I. The mean values for each group in Table 2 show a significant difference in HDL-cholesterol and triglyceride levels according to corpulence groups. Two-by-two analysis showed that triglyceridemia was different between mildly and massively obese group, as well as between the non-obese and each obese group, while HDLcholesterol was not. The difference in LDLcholesterol between the 3 corpulence groups was close to significance (P = 0.07).
Results In the population taken as a whole, cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, apo A-I, apo B, systolic blood pressure, diastolic blood pressure were highly correlated with age. The relationship between HDL-cholesterol and BMI was significantly negative (Table 1). The other risk factors selected were positively correlated with BMI. After adjustment for age, correlations of BMI persisted with HDL-cholesterol
TABLE 2 BMI, TRIGLYCERIDE, CORPULENCE
HDL-CHOLESTEROL,
LDL-CHOLESTEROL
AND TOTAL
CHOLESTEROL
ACCORDING
TO
Values are mean k SD.
n BMI (kg/m*) Total cholesterol (mg/dl) Triglyceride (mg/dl) HDL-cholesterol (mg/dl) LDL-cholesterol (mg/dl) * * *
Non-obese
Mildly obese
226
233
25.2+
1.5
211.3+41.2 78.8 f 39.6 a 61.8 f 18.2 a 134.3 f 36.4
Massively obese
P
194
29.8+
1.4
219.8 + 104.9 f 55.9+ 144.1*
49.0 58.6 ’ 18.0 h 41.3
35.6+
4.6
225.6 k 43.8 124.4k71.6 ’ 54.0 * 19.4 h 148.0 + 36.9
*** llS
*** ***
IlS
Significantly different (P < 0.001) between the 3 corpulence groups, after adjustment for age. Values with different superscripts are significantly different.
122 TABLE AGE,
3 BMI, SELECTED
CHD RISK FACTORS
RELATED
TO ALCOHOL
INTAKE
IN THE STUDY
GROUP
Values are means + SD. Drinkers
(by daily alcohol
Non-drinkers (n=308)
4%
Total cholesterol (mg/dl) Triglycerides (mg/dl) HDL-cholesterol (mg/dl) LDL-cholesterol (mg/dl) APO A-l (g/I) APO B (g/I) Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg)
> 10 g/d (n =187)
< 10 g/d (n =158)
33.3k13.9 30.8* 5.8
BMI (kg/m’) CHD risk factors
intake)
38.1 f 12.1 30.2+ 5.1
210.6 k 40.3 98.7 + 59.0 54.5 * 11.9 137.5 + 35.3 124.7 + 29.8 101.8+31.5
215.4+ 94.5 f 58.7+ 138.7+ 131.8* 104.1 f
131.1 f 19.0
129.3 * 18.5
80.1+ 11.2
78.8 k 10.2
All drinkers (n = 345)
42.5*11.3 *** 30.2+ 5.6
45.0 55.1 19.2 38.2 31.1 34.8
40.5 * 11.9 +++ 30.3* 5.6
234.4 f 49.0 * 112.6k64.9 * 61.1+ 19.0 151.8*43.0 134.1 + 32.6 113.2 f 37.9
225.7 + 48.1 104.3k61.2 60.0& 19.1 ++ 145.8 f 41.3 133.0* 31.9 + 109.3 f 36.8
134.7 f 18.3
132.3 f 18.9
93.1 f 10.7 *
81.2+ 10.7
Differences between non drinkers and all drinkers statistically significant (’ P < 0.05, ++ P < 0.01, +++ P < 0.001). Differences between drinkers according to intake (* P < 0.05, * * * P < 0.001). Relationships between CHD ri‘sk factors and alcohol were analyzed after adjustment for age.
Characteristics of the study population according to alcohol intake are presented in Table 3. Mean intake was moderate within a wide range. Among the subjects, 308 were non-drinkers and 158 drank less than 10 g ethanol per day (mean f SD: 5.0 f 2.1 g/d), 187 more than 10 g (mean + SD: 27.3 * 20.7 g/d). The mean levels of selected CHD risk factors were within normal values. Drinkers were older than non-drinkers, and among drinkers, those drinking less than 10 g per day
TABLE SERUM
were younger. In the population as a whole as well as in each corpulence group, relationships between selected risk factors and alcohol were examined after adjustment for age, because all were significantly correlated with age. HDL-cholesterol and apo A-I were higher in drinkers than in nondrinkers, but among drinkers, there was no difference depending on the level of ethanol intake. Total cholesterol, triglycerides and diastolic blood pressure were higher in the heavier drinkers (more
4 HDL-CHOLESTEROL
(mg/dl) Drinkers
(by daily ethanol
Non-drinkers Non-obese (BMI < 27.3) Mildly obese (27.3 < BMI < 32.3) Massively obese (BMI > 32.3)
AS A FUNCTION
OF CORPULENCE
STATUS
AND ALCOHOL
r
intake)
d 10 g/d
INTAKE
> 10 g/d
All drinkers
59*16
63+18
68+18
65k18
(106)
(57)
(63)
(120)
53+17
57*19
59f17
58k18
(98)
(63)
(72)
(135)
53f19
55+20
56+20
55519
(104)
(38)
(52)
(90)
Expressed as mean f SD; number of subjects in parentheses. * * Significantly different from non drinkers (P < 0.01). after adjustment for age. r = partial correlation coefficient between HDL-cholesterol and alcohol intake after adjustment
**
0.26 ++
0.05
0.02
for age; ++ P c 0.01.
123 than 10 g per day). LDL-cholesterol tended to be elevated in heavier drinkers compared to moderate, but the difference was not statistically significant (P = 0.09). Systolic blood pressure, apo B and HDL-cholesterol/ape A-I ratio could not be statistically related to alcohol intake. Table 4 shows HDL-cholesterol concentrations according to alcohol intake in each corpulence group. In non-obese women, HDL-cholesterol was significantly higher in drinkers than in nondrinkers (P = 0.006); the difference persisted after adjustment for 2 potential perturbating factors: cholesterol and total fat intake. In mildly obese and in massively obese women, alcohol intake was not associated with a higher level of HDLcholesterol. The multivariate model indicated significant effects on HDL-cholesterol levels of obesity (P = 0.001) alcohol intake (P = 0.001) as well as of the interaction term between obesity and alcohol (P = 0.012), showing that the effect of alcohol was not the same within each group of corpulence. Consequently, the correlation between alcohol and HDL-cholesterol was calculated separately for each group and found to be significant only in the non-obese (r = 0.26, P = 0.006).
Discussion
The elevation of triglycerides, LDL-cholesterol, apo B and blood pressure with corpulence and age is in agreement with studies previously reported [9,11,13]. As expected [9,12,15,16], HDL-cholesterol was lower in obese subjects. As in other studies [22,23], total cholesterol did not appear to be linked to overweight because of the inverse variation of its two major components (LDL and HDL) with corpulence (Table 2). The absence of decrease in apo A-I concentration with increasing body weight is consistent with previous results [23]. Thus, the ratio of HDL cholesterol to apo A-I decreased with corpulence consistently with reported data on HDL subfractions, HDL, and HDL, [16,25,26]: obesity preferentially decreases HDL,, which has a higher cholesterol/ape A-I ratio than HDL,. The relationship between BMI and HDL-cholesterol was not continuous: both mildly and severely obese had lower concentrations than non-obese, but there was no difference
according to the degree of obesity, which is consistent with the results of a previous study [16]. Alcohol intake was not associated with higher body weights. This could be due to the poor efficiency of alcohol-derived energy production [27,28]. As a matter of fact, addition of alcohol calories to the diet has been shown not to be associated with any weight gain even when reaching 500-640 kcal extra daily [6,29,30]. Most of the previous studies relating alcohol to HDL-cholesterol have been concerned with relatively high intakes, whether in controlled intervention studies on non-alcoholic volunteers [6,29,30] or in epidemiological studies [31]. We show that even a low ethanol intake (< 10 g per day) is associated with elevated HDL-cholesterol and apo A-I. This result should be put in parallel with the epidemiological data reporting a decrease in the incidence of CHD even when daily alcohol intake is less than 5 g [l]. The question does arise, however, of whether this potentially favorable effect of a low alcohol intake through HDL-cholesterol might be counterbalanced by adverse effects. Although total cholesterol, serum triglycerides and diastolic blood pressure were significantly higher for alcohol intakes higher than 10 g per day, they were not for lower intakes, which is in agreement with previous studies [6,32]. In heavier drinkers, although both triglycerides and cholesterol were elevated, apo B, as reported by others [33], was not. The relationship of alcohol with HDLcholesterol was not the same in all corpulence groups. A positive correlation was evidenced between a moderate level of alcohol intake and HDL-cholesterol in non-obese subjects (P = 0.006) as reported in the general population [31]. On the contrary, this relationship disappeared both in mildly obese (P = 0.395) and in massively obese women (P = 0.864). Thus, obesity could be one of the reasons for the differences in individual responses of HDL-cholesterol to alcohol. However, our population was female and the results should not be projected on males. How can obesity prevent HDL-cholesterol enhancement by alcohol intake? The factors which are associated with weight gain could be related to those which limit the expansion of the HDL pool. Prominent among those is the capacity for HDL
124 to acquire by-products of lipolysis [34-361. Alcohol elevates VLDL synthesis [37,38] and lipoprotein lipase activity [4], the conjunction of which should result in an increased transfer of surface elements from VLDL to the HDL pool. For this part, obesity has been reported to be associated with a slowdown in lipolysis [39,40], possibly resulting in a defective transfer of surface elements to HDL. This could limit the effects of alcohol. In conclusion, although a low level of alcohol intake enhanced HDL-cholesterol in non-obese women without obvious adverse effect, this elevation did not exist in obese subjects, possibly due to a slowdown of lipolysis linked to obesity. Controlled intervention studies in non-alcoholic obese volunteers are needed to clarify the relationship between alcohol and lipoproteins in obesity, and might throw a new light on the factors controlling the size of the HDL pool. Acknowledgements The skilful technical assistance of Genevieve Jauzon, Catherine Mougeot and Marie de Seze, dietitians, is gratefully acknowledged. Special thanks are due to Nelly Bertazzolo for expert secretarial assistance. References 1 Stampfer, M.J., Colditz, G.A., Willet, W.C., Speizer, F.E. and Hennekens, C.H., A prospective study of moderate alcohol consumption and the risk of coronary disease and stroke in women, N. Engl. J. Med., 319 (1988) 267. 2 Gordon, T. and Kannel, W.B., Drinking habits and cardiovascular disease: The Framingham Study, Am. Heart J., 105 (1983) 667. 3 Klatsky, A.L., Friedman, G.D. and Siegelaub, A.B., Alcohol and mortality: a tenyear Kaiser-Permanente experience, Ann. Intern; Med., 95 (1981) 139. 4 Belfrage, P., Berg, B., Hagerstrand, I., Nilsson-Ehle, P., Tornquist, H. and Wiebe, T., Alterations of lipid metabolism in healthy volunteers during long term ethanol intake, Eur. J. Clin. Invest., 7 (1977) 127. 5 Thornton, J., Symes, C. and Heaton, K., Moderate alcohol intake reduces bile cholesterol saturation and raises HDL cholesterol, Lance& 2 (1983) 819. 6 Bertiere, M.C., Betoulle, D., Apfelbaum, M. and GirardGloba, A., Time-course, magnitude and nature of the changes induced in HDL by moderate alcohol intake in young non-drinking males, Atherosclerosis, 61 (1986) 7. 7 Castelli, W.P., Doyle, J.T., Gordon, T., Hames, C.G.,
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ATHERO
119 Ltd.
04436
Lack of association between dietary alcohol and HDL-cholesterol concentrations in obese women Jacques Fricker,
Fr&dQic Fumeron, Samira Chabchoub, and Anik Girard-Globa
INSERM
Marian Apfelbaum
U. 286, Human Nutrition, Medical School X. Bichat, Paris (France) (Received 16 June, 1989) (Revised, received 21 November, 1989) (Accepted 23 November, 1989)
Summary
The relationships of alcohol intake and corpulence to HDL-cholesterol were studied in 653 women taking medical advice about body weight. The body mass index (BMI) was positively correlated with triglyceride and negatively with HDL-cholesterol. The relation between BMI and HDL-cholesterol was discontinuous. Total cholesterol, triglycerides and diastolic blood pressure were increased for alcohol intakes greater than 10 g/d regardless of body weight. Alcohol intake was associated with higher concentrations of HDL-cholesterol (P = 0.006) in non obese (BMI = 25.2 f 1.5 kg/m*) subjects, but not in mildly (27.3 < BMI < 32.3) or massively (BMI >, 32.3) obese subjects. The fact that HDL concentrations were not associated with alcohol intake in obese patients suggests that (1) alcohol acts on the HDL pool through one of the pathways which are perturbed in obesity, possibly lipolysis, (2) obesity is one of the reasons for the differences in individual responses of HDL-cholesterol to alcohol, (3) myocardial infarction might not be inversely correlated with alcohol intake in the obese as it is in the non-obese population.
Key words:
Alcohol;
Cholesterol;
High density
lipoprotein;
Introduction
A moderate level of alcohol intake has repeatedly been found to be associated with a decreased incidence of coronary heart disease (CHD) [l-3]. Alcohol is also reported to increase con-
Correspondence to: Dr. Jacques Fricker, INSERM Human Nutrition, Medical School Hapital X. Bichat, Henri Huchard, F-75018 Paris, France. 0021-9150/90/$03.50
0 1990 Elsevier Scientific
U.286, 16 rue
Publishers
Ireland,
Obesity;
Triglyceride
centrations of high density lipoprotein (HDL)cholesterol [4-61. Since a negative relationship exists between HDL-cholesterol and the incidence of CHD [7,8], it has been postulated that the negative association of alcohol intake with CHD might be partly mediated by the increase of HDL. The data are, however, suggestive of differences in individual responses of HDL-cholesterol to alcohol. Epidemiological studies demonstrate that obesity is on the contrary associated with an increased risk of coronary heart disease [9,10]. Ltd.
120 Although obesity per se might be an independent risk factor [ll], the relationship could also be mediated by its association with other cardiovascular risk factors, such as hypertension, non insulin-dependent diabetes and lipoprotein abnormalities [9,12]; increased concentrations of serum very low density lipoproteins (VLDL) have frequently been reported in obese [13,14], as well as a reduction of HDL-cholesterol, occurring even in normotriglyceridemic subjects [9,12,15,16]. The present work was designed to determine if, amongst an overweight population, alcohol does increase HDL-cholesterol despite the alteration in HDL metabolism due to obesity, or whether the factors underlying obesity are one of the reasons for the differences in individual responses of HDL-cholesterol to alcohol. Methods Subjects The study was carried out on 653 women seeking medical advice about body weight in the Nutrition Clinic of Bichat Hospital. Body weight was measured without shoes or clothes to the nearest 0.1 kg. Height was also measured without shoes to the nearest 1 cm. The body mass index (BMI; kg/m2) was used to assess corpulence. In the months before the study all subjects had been on spontaneous diet. None received medications that might affect their lipid levels. Most were sedentary (less than 1 h physical exercise per day). Although all subjects consulted the weight control unit because of a concern about body weight, some were not obese but only moderately overweight. Following the guidelines of the National Health and Nutrition Examination Surveys, 1976-80 (NHANES II) [17], the women were distributed into 3 groups: 226 non-obese (BMI < 27.3), 233 mildly obese (27.3 G BMI < 32.3), and 194 severely obese (BMI > 32.3). Supine systolic and diastolic blood pressures were measured at the study-site after a 5-min rest. Food intake Intake was assessed by use of a dietary history questionnaire covering a period of 1 month. 450 questions cover successively, breakfast, lunch, dinner, snacks and nibbling. For lunch and dinner, an
alternative is proposed: “cooked” or “uncooked”, which reflects the tendency for a difference between formal meals versus sandwiches or fast food. For the formal meals, traditional phases (starter, main dish, cheese, dessert, bread, drinks) are proposed. Specific questions are designed to cover alcohol intake over 24 h, distinguishing between coktail-time drinks, meal-time, after-meal, between-meals and nocturnal drinks. For each period a large choice of usual items are suggested. The subject answers in terms of weekly frequency for the meal, the phase, the food or the drink. Foods consumed very occasionally can be recorded with a frequency smaller than one. The amounts of alcohol are estimated through independent but overlapping questions regarding the size of glasses, the level of filling and number of refills and the number of bottles drunk a week. Calibrated glasses help the subject to better estimate amounts. The filled questionnaire was reviewed by a dietitian together with the patient, and cross-checked for reliability and coherence of the information on amounts and frequencies. The nutritional data were computerized using a compilation of 2 food tables [19,20]. The stated purpose of these enquiries was to prescribe a personalized diet fitting the patient’s habits. Neither the dietician, nor the patient were aware of the epidemiological aspect of these enquiries, in order to attenuate the observer effect linked to dietary epidemiological studies. The efficiency of this questionnaire had been assessed elsewhere against estimated total energy expenditure [18]. Lipid, lipoprotein and apoprotein measurements Blood samples were collected after an overnight fast. Serum cholesterol and triglycerides were assayed using commercial test kits (Biotrol, Lyon, France). VLDL were prepared by ultracentrifugation: 2 ml serum were diluted with 1 ml 0.9% NaCl and centrifuged for 3 h (10 o C) in a Kontron TFT 45,6 rotor at 45000 rpm. Cholesterol was determined in VLDL and infranatant by the same methods as in the serum. LDL in infranatant were precipitated by phosphotungstate-MgCl 2 and cholesterol assayed in the supernatant considered as the HDL fraction [21]. LDL cholesterol was determined by substraction. Serum apoproteins (apo A-I and B) concentrations were determined
121 by the Laurel1 France).
method
(“Apofilm”
Sebia,
TABLE 1
Issy,
CORRELATION COEFFICIENTS OF SELECTED RISK FACTORS WITH AGE AND BMI
Stutistics Statistical analysis was performed using the MGLH module of the Systat program [22]. Relationships between continuous variables were assessed by the correlation coefficients. Means were compared by analysis of variance or analysis of covariance after inclusion of age in the model. A multiple regression analysis was performed with HDL cholesterol as the dependent variable and corpulence status, alcohol intake, age and the interaction term between alcohol consumption and corpulence as independent predictors. Since the interaction between obesity and alcohol intake was found to be significant, a model including alcohol and age was tested in each class of corpulence. Triglyceride values were tested after log transformation.
BMI
Age Cholesterol LDL-cholesterol HDL-cholesterol Triglycerides Systolic blood pressure Diastolic blood pressure Apo B Apo A-I HDL-C/APO A-I ** ***
0.53 0.45 0.14 0.27
CHD
*** *** *** ***
0.11 0.14 -0.19 0.31
** *** *** ***
0.44 * * *
0.29 * * *
0.35 * * * 0.38 * * * 0.19 *** ns
0.26 *** 0.18 * * * ns -0.18
***
P
and each selected risk factor, except total cholesterol. Apo A-I was not correlated with corpulence; this resulted in a negative relationship between BMI and the ratio of HDL-cholesterol to apo A-I. The mean values for each group in Table 2 show a significant difference in HDL-cholesterol and triglyceride levels according to corpulence groups. Two-by-two analysis showed that triglyceridemia was different between mildly and massively obese group, as well as between the non-obese and each obese group, while HDLcholesterol was not. The difference in LDLcholesterol between the 3 corpulence groups was close to significance (P = 0.07).
Results In the population taken as a whole, cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, apo A-I, apo B, systolic blood pressure, diastolic blood pressure were highly correlated with age. The relationship between HDL-cholesterol and BMI was significantly negative (Table 1). The other risk factors selected were positively correlated with BMI. After adjustment for age, correlations of BMI persisted with HDL-cholesterol
TABLE 2 BMI, TRIGLYCERIDE, CORPULENCE
HDL-CHOLESTEROL,
LDL-CHOLESTEROL
AND TOTAL
CHOLESTEROL
ACCORDING
TO
Values are mean k SD.
n BMI (kg/m*) Total cholesterol (mg/dl) Triglyceride (mg/dl) HDL-cholesterol (mg/dl) LDL-cholesterol (mg/dl) * * *
Non-obese
Mildly obese
226
233
25.2+
1.5
211.3+41.2 78.8 f 39.6 a 61.8 f 18.2 a 134.3 f 36.4
Massively obese
P
194
29.8+
1.4
219.8 + 104.9 f 55.9+ 144.1*
49.0 58.6 ’ 18.0 h 41.3
35.6+
4.6
225.6 k 43.8 124.4k71.6 ’ 54.0 * 19.4 h 148.0 + 36.9
*** llS
*** ***
IlS
Significantly different (P < 0.001) between the 3 corpulence groups, after adjustment for age. Values with different superscripts are significantly different.
122 TABLE AGE,
3 BMI, SELECTED
CHD RISK FACTORS
RELATED
TO ALCOHOL
INTAKE
IN THE STUDY
GROUP
Values are means + SD. Drinkers
(by daily alcohol
Non-drinkers (n=308)
4%
Total cholesterol (mg/dl) Triglycerides (mg/dl) HDL-cholesterol (mg/dl) LDL-cholesterol (mg/dl) APO A-l (g/I) APO B (g/I) Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg)
> 10 g/d (n =187)
< 10 g/d (n =158)
33.3k13.9 30.8* 5.8
BMI (kg/m’) CHD risk factors
intake)
38.1 f 12.1 30.2+ 5.1
210.6 k 40.3 98.7 + 59.0 54.5 * 11.9 137.5 + 35.3 124.7 + 29.8 101.8+31.5
215.4+ 94.5 f 58.7+ 138.7+ 131.8* 104.1 f
131.1 f 19.0
129.3 * 18.5
80.1+ 11.2
78.8 k 10.2
All drinkers (n = 345)
42.5*11.3 *** 30.2+ 5.6
45.0 55.1 19.2 38.2 31.1 34.8
40.5 * 11.9 +++ 30.3* 5.6
234.4 f 49.0 * 112.6k64.9 * 61.1+ 19.0 151.8*43.0 134.1 + 32.6 113.2 f 37.9
225.7 + 48.1 104.3k61.2 60.0& 19.1 ++ 145.8 f 41.3 133.0* 31.9 + 109.3 f 36.8
134.7 f 18.3
132.3 f 18.9
93.1 f 10.7 *
81.2+ 10.7
Differences between non drinkers and all drinkers statistically significant (’ P < 0.05, ++ P < 0.01, +++ P < 0.001). Differences between drinkers according to intake (* P < 0.05, * * * P < 0.001). Relationships between CHD ri‘sk factors and alcohol were analyzed after adjustment for age.
Characteristics of the study population according to alcohol intake are presented in Table 3. Mean intake was moderate within a wide range. Among the subjects, 308 were non-drinkers and 158 drank less than 10 g ethanol per day (mean f SD: 5.0 f 2.1 g/d), 187 more than 10 g (mean + SD: 27.3 * 20.7 g/d). The mean levels of selected CHD risk factors were within normal values. Drinkers were older than non-drinkers, and among drinkers, those drinking less than 10 g per day
TABLE SERUM
were younger. In the population as a whole as well as in each corpulence group, relationships between selected risk factors and alcohol were examined after adjustment for age, because all were significantly correlated with age. HDL-cholesterol and apo A-I were higher in drinkers than in nondrinkers, but among drinkers, there was no difference depending on the level of ethanol intake. Total cholesterol, triglycerides and diastolic blood pressure were higher in the heavier drinkers (more
4 HDL-CHOLESTEROL
(mg/dl) Drinkers
(by daily ethanol
Non-drinkers Non-obese (BMI < 27.3) Mildly obese (27.3 < BMI < 32.3) Massively obese (BMI > 32.3)
AS A FUNCTION
OF CORPULENCE
STATUS
AND ALCOHOL
r
intake)
d 10 g/d
INTAKE
> 10 g/d
All drinkers
59*16
63+18
68+18
65k18
(106)
(57)
(63)
(120)
53+17
57*19
59f17
58k18
(98)
(63)
(72)
(135)
53f19
55+20
56+20
55519
(104)
(38)
(52)
(90)
Expressed as mean f SD; number of subjects in parentheses. * * Significantly different from non drinkers (P < 0.01). after adjustment for age. r = partial correlation coefficient between HDL-cholesterol and alcohol intake after adjustment
**
0.26 ++
0.05
0.02
for age; ++ P c 0.01.
123 than 10 g per day). LDL-cholesterol tended to be elevated in heavier drinkers compared to moderate, but the difference was not statistically significant (P = 0.09). Systolic blood pressure, apo B and HDL-cholesterol/ape A-I ratio could not be statistically related to alcohol intake. Table 4 shows HDL-cholesterol concentrations according to alcohol intake in each corpulence group. In non-obese women, HDL-cholesterol was significantly higher in drinkers than in nondrinkers (P = 0.006); the difference persisted after adjustment for 2 potential perturbating factors: cholesterol and total fat intake. In mildly obese and in massively obese women, alcohol intake was not associated with a higher level of HDLcholesterol. The multivariate model indicated significant effects on HDL-cholesterol levels of obesity (P = 0.001) alcohol intake (P = 0.001) as well as of the interaction term between obesity and alcohol (P = 0.012), showing that the effect of alcohol was not the same within each group of corpulence. Consequently, the correlation between alcohol and HDL-cholesterol was calculated separately for each group and found to be significant only in the non-obese (r = 0.26, P = 0.006).
Discussion
The elevation of triglycerides, LDL-cholesterol, apo B and blood pressure with corpulence and age is in agreement with studies previously reported [9,11,13]. As expected [9,12,15,16], HDL-cholesterol was lower in obese subjects. As in other studies [22,23], total cholesterol did not appear to be linked to overweight because of the inverse variation of its two major components (LDL and HDL) with corpulence (Table 2). The absence of decrease in apo A-I concentration with increasing body weight is consistent with previous results [23]. Thus, the ratio of HDL cholesterol to apo A-I decreased with corpulence consistently with reported data on HDL subfractions, HDL, and HDL, [16,25,26]: obesity preferentially decreases HDL,, which has a higher cholesterol/ape A-I ratio than HDL,. The relationship between BMI and HDL-cholesterol was not continuous: both mildly and severely obese had lower concentrations than non-obese, but there was no difference
according to the degree of obesity, which is consistent with the results of a previous study [16]. Alcohol intake was not associated with higher body weights. This could be due to the poor efficiency of alcohol-derived energy production [27,28]. As a matter of fact, addition of alcohol calories to the diet has been shown not to be associated with any weight gain even when reaching 500-640 kcal extra daily [6,29,30]. Most of the previous studies relating alcohol to HDL-cholesterol have been concerned with relatively high intakes, whether in controlled intervention studies on non-alcoholic volunteers [6,29,30] or in epidemiological studies [31]. We show that even a low ethanol intake (< 10 g per day) is associated with elevated HDL-cholesterol and apo A-I. This result should be put in parallel with the epidemiological data reporting a decrease in the incidence of CHD even when daily alcohol intake is less than 5 g [l]. The question does arise, however, of whether this potentially favorable effect of a low alcohol intake through HDL-cholesterol might be counterbalanced by adverse effects. Although total cholesterol, serum triglycerides and diastolic blood pressure were significantly higher for alcohol intakes higher than 10 g per day, they were not for lower intakes, which is in agreement with previous studies [6,32]. In heavier drinkers, although both triglycerides and cholesterol were elevated, apo B, as reported by others [33], was not. The relationship of alcohol with HDLcholesterol was not the same in all corpulence groups. A positive correlation was evidenced between a moderate level of alcohol intake and HDL-cholesterol in non-obese subjects (P = 0.006) as reported in the general population [31]. On the contrary, this relationship disappeared both in mildly obese (P = 0.395) and in massively obese women (P = 0.864). Thus, obesity could be one of the reasons for the differences in individual responses of HDL-cholesterol to alcohol. However, our population was female and the results should not be projected on males. How can obesity prevent HDL-cholesterol enhancement by alcohol intake? The factors which are associated with weight gain could be related to those which limit the expansion of the HDL pool. Prominent among those is the capacity for HDL
124 to acquire by-products of lipolysis [34-361. Alcohol elevates VLDL synthesis [37,38] and lipoprotein lipase activity [4], the conjunction of which should result in an increased transfer of surface elements from VLDL to the HDL pool. For this part, obesity has been reported to be associated with a slowdown in lipolysis [39,40], possibly resulting in a defective transfer of surface elements to HDL. This could limit the effects of alcohol. In conclusion, although a low level of alcohol intake enhanced HDL-cholesterol in non-obese women without obvious adverse effect, this elevation did not exist in obese subjects, possibly due to a slowdown of lipolysis linked to obesity. Controlled intervention studies in non-alcoholic obese volunteers are needed to clarify the relationship between alcohol and lipoproteins in obesity, and might throw a new light on the factors controlling the size of the HDL pool. Acknowledgements The skilful technical assistance of Genevieve Jauzon, Catherine Mougeot and Marie de Seze, dietitians, is gratefully acknowledged. Special thanks are due to Nelly Bertazzolo for expert secretarial assistance. References 1 Stampfer, M.J., Colditz, G.A., Willet, W.C., Speizer, F.E. and Hennekens, C.H., A prospective study of moderate alcohol consumption and the risk of coronary disease and stroke in women, N. Engl. J. Med., 319 (1988) 267. 2 Gordon, T. and Kannel, W.B., Drinking habits and cardiovascular disease: The Framingham Study, Am. Heart J., 105 (1983) 667. 3 Klatsky, A.L., Friedman, G.D. and Siegelaub, A.B., Alcohol and mortality: a tenyear Kaiser-Permanente experience, Ann. Intern; Med., 95 (1981) 139. 4 Belfrage, P., Berg, B., Hagerstrand, I., Nilsson-Ehle, P., Tornquist, H. and Wiebe, T., Alterations of lipid metabolism in healthy volunteers during long term ethanol intake, Eur. J. Clin. Invest., 7 (1977) 127. 5 Thornton, J., Symes, C. and Heaton, K., Moderate alcohol intake reduces bile cholesterol saturation and raises HDL cholesterol, Lance& 2 (1983) 819. 6 Bertiere, M.C., Betoulle, D., Apfelbaum, M. and GirardGloba, A., Time-course, magnitude and nature of the changes induced in HDL by moderate alcohol intake in young non-drinking males, Atherosclerosis, 61 (1986) 7. 7 Castelli, W.P., Doyle, J.T., Gordon, T., Hames, C.G.,
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