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ALCOHOL AND HEALTH
Morten Grønbæk
National Institute of Public Health
Copenhagen, Denmark
Mortality ->Detrimental Effects: Cirrhosis, Cancer
Positive Effects: Cardiovascular Disease
Alcohol and Health
Mortality ->Detrimental Effects: Cirrhosis, Cancer
Positive Effects: Cardiovascular Disease
Alcohol and HealthSomatic
Mortality ->Detrimental Effects: Cirrhosis, Cancer
Positive Effects: Cardiovascular Disease
Alcohol and HealthSomatic
Epidemiological evidence
0,4
0,6
0,8
1
1,2
1,4
1,6
1,8
0 <1 1 2 3 4 5 6+
Alcohol, drinks per day
Mor
tali
ty
Boffetta et al, Epidemiology 1990
Alcohol and mortality
0,4
0,6
0,8
1
1,2
1,4
1,6
1,8
0 <1 1 2 3 4 5 6+
Alcohol, drinks per day
Mor
tali
ty
Boffetta et al, Epidemiology 1990
Alcohol and mortality
Alcohol and mortality
0,4
0,6
0,8
1
1,2
1,4
1,6
1,8
0 <1 1 2 3 4 5 6+
Alcohol, drinks per day
Mor
tali
ty
Boffetta et al, Epidemiology 1990
0,2
0,4
0,6
0,8
1
1,2
1,4
1,6
1,8
0 <1 1 2 3 4 5 6+
Alcohol, drinks per day
Rel
ativ
e m
orta
lity
All
Cancer
Coronary heart disease
Boffetta et al, Epidemiology 1990
Alcohol and cause specific mortality
0
2
4
6
8
10
Alcohol intake, drinks per week
Relative risk
< 1 1 - 7 8 - 21 22 - 35 > 35
Alcohol and alcoholic cirrhosis
Drinks per week
Relative risk
< 1 1-6 7-13 14-27 28-41 42-69 >700
2
4
6
8
10
12
14
16
18
20
Alcohol and alcoholic cirrhosisSex differences
Men
WomenP < 0.05
Becker U et al., Hepatology 1996
Alcohol intake, drinks per day
The Copenhagen Alcohol Cohort , N=9.000
5-9 10-14 15-19 20-24 25-29 30-34 35+
Number of individuals 439 1134 1284 1192 846 535 722
Number of deaths from alcoholic cirrhosis 32 64 59 47 30 18 35
Men, percent 49 59 72 75 83 86 89
Kamper-Jørgensen M et al, J Hepatol 2004
Alcohol intake, drinks per day
The Copenhagen Alcohol Cohort , N=9.000
5-9 10-14 15-19 20-24 25-29 30-34 35+
Number of individuals 439 1134 1284 1192 846 535 722
Number of deaths from alcoholic cirrhosis 32 64 59 47 30 18 35
Men, percent 49 59 72 75 83 86 89
Kamper-Jørgensen M et al, J Hepatol 2004
Alcohol intake, drinks per day
The Copenhagen Alcohol Cohort , N=9.000
5-9 10-14 15-19 20-24 25-29 30-34 35+
Number of individuals 439 1134 1284 1192 846 535 722
Number of deaths from alcoholic cirrhosis 32 64 59 47 30 18 35
Men, percent 49 59 72 75 83 86 89
SMR, cirrhosis: Men 27 Women 35
Kamper-Jørgensen M et al, J Hepatol 2004
Alc cir
Men, amount
Kamper-Jørgensen M et al, J Hepatol 2004
The Copenhagen Alcohol Cohort
Men, duration
Kamper-Jørgensen M et al, J Hepatol 2004
The Copenhagen Alcohol Cohort
Alcohol and Breast CancerCopenhagen Centre for Prospective Population Studies
0
0,5
1
1,5
2
2,5
3
3,5
< 1 1-6 7-13 14-27 > 27
Total alcohol intake
Rela
tiv
e r
isk
of
brea
st c
an
cer
Petri A et al, Alc Clin Exp Res 2004
Tjønneland A et al, Cancer Causes and Control 2003; 14: 277–284
Alcohol and Breast Cancer
Diet Cancer and Health Study
0,5
0,6
0,7
0,8
0,9
1
1,1
1,2
1,3
1,4
1,5
1,6
1,7
1,8
1,9
2
0 1 2 3 4 5 6
Alcohol, drinks per day
Rel
ativ
e R
isk
Alcohol and Breast CancerPooled analysis
Ellison RC, Am J Epidemiol 2001
0,5
0,6
0,7
0,8
0,9
1
1,1
1,2
1,3
1,4
1,5
1,6
1,7
1,8
1,9
2
0 1 2 3 4 5 6
Alcohol, drinks per day
Rel
ativ
e R
isk
Alcohol and Breast CancerDose-response or threshold?
Upper digestive tract cancer
0
2
4
6
8
10
12
14
0 1-6 7-21 22-41 42-69 69+
Relative risk
Alcohol, drinks per week
Grønbæk et al, BMJ 1998
Alcohol and mortality
0,4
0,6
0,8
1
1,2
1,4
1,6
1,8
0 <1 1 2 3 4 5 6+
Alcohol, drinks per day
Mor
tali
ty
Boffetta et al, Epidemiology 1990
Alcohol and cardiovascular disease
Clinical and experimental evidence:
- High density lipoprotein (HDL)
- Low density lipoprotein (LDL)
- Platelet aggregation
- Fibrinogen
- Fibrinolysis
- Blood pressure
Age, Sex, Genes
Drinking pattern
Factors influencing the association between alcohol and cardiovascular disease
Age, Sex, Genes
Drinking pattern
Factors influencing the association between alcohol and cardiovascular disease
0,5
0,6
0,7
0,8
0,9
1,0
1,1
1,2
1,3
1,4
1,5
0 0.1-1.4 1.5-4.9 5.0-14.9 15.0-29.9 30+
Alcohol, grams per day
Mo
rta
lity
Fuchs et al, NEJM 1995
Alcohol and mortality: AgeNurses’ Health Study
0,5
1,0
1,5
2,0
2,5
3,0
0 0.1-1.4 1.5-29.9 30+
Average alcohol intake (g/day)
Mo
rtal
ity
Fuchs et al, NEJM 1995
Alcohol and mortality: AgeNurses’ Health Study
34-39 y
40-49 y
50-59 y
60+ y
Genetics: Alcohol dehydrogenase
ADH3: Functional polymorphism causing an ~3 fold difference in activity
p(ADH31) = 0.6 (fast allele)
p(ADH32) = 0.4 (slow allele)
Hines et al.: NEJM: 2001
(fast) (slow) (fast) (slow)
ADH, alcohol and myocardial infarction
Age, Sex, Genes
Drinking pattern
Factors influencing the association between alcohol and cardiovascular disease
Drinking pattern:Meal related alcohol intakeType of alcoholBinge vs steady intake
Factors influencing the association between alcohol and cardiovascular disease
Alcohol intake consumed with meals and myocardial infarction
Mukamal et al.NEJM 2003;348:109-18
Variable 0.1-4.9 g/day 5.0-29.9 g/day ≥ 30.0 g/day P value
< 25% Relative risk
95% CI1.00
-
0.67
0.45-0.99
0.57
0.32-1.03
0.05
25-74% Relative risk
95% CI1.00
-
0.78
0.29-2.07
0.51
0.15-1.77
0.28
≥ 75%
Relative risk
95% CI
1.00
-
0.92
0.52-1.63
0.33
0.09-1.27
0.16
Different alcoholic beverages and cardiovascular disease mortality
0,2
0,4
0,6
0,8
1
1,2
1,4
1,6
1,8
Never Monthly Weekly Daily,1-2 Daily,3-5
Beverage specific alcohol consumption
Rel
ativ
e ri
sk
Wine
Beer
Spirits
Grønbæk et al., BMJ 1995
Alcohol, wine and mortalityCopenhagen Centre of Prospective Population Studies
0,4
0,6
0,8
1
1,2
1,4
1,6
1,8
0 1-7 8-21 22-35 >35
Alcohol Consumption, drinks/wk
Mor
talit
y
0
1-30
>30
Percent wine of alcohol intake
Grønbæk et al Ann Int Med 2000; 133(6):411-419
0,4
0,6
0,8
1
1,2
1,4
1,6
0 1-7 8-21 >21
Alcohol Consumption, drinks/wk
Rel
ativ
e M
orta
lity
fro
m C
HD
Grønbæk et al Ann Int Med; 133(6):411-419
Alcohol, wine and mortality from CHD
Non-wine drinkers
Wine drinkers
0,4
0,6
0,8
1
1,2
1,4
1,6
0 1-7 8-21 22-35 >35
Alcohol Consumption, drinks/wk
Rel
ativ
e M
orta
lity
fro
m C
ance
r
Grønbæk et al Ann Int Med; 133(6):411-419
Alcohol, wine and mortality from cancer
Type of alcohol and mortalityBritish Regional Heart Study
Beer (N=4101)
Spirits (N=1724)
Wine (N=1035)
All cause mortality Age-adj RR 1.00 0.94 (0.83-1.07) 0.58 (0.47-0.70) Adjusted RR 1.00 0.99 (0.86-1.13) 0.80 (0.65-0.98)
Cardiovascular mortality Age-adj RR 1.00 1.04 (0.86-1.25) 0.54 (0.40-0.73) Adjusted RR (+) 1.00 1.03 (0.84-1.26) 0.72 (0.52-0.98)
Wannamethee and Shaper Am J Publ Health 1999
0
5
10
15
20
0 1-7 8-21 22-35 >35
Total alcohol intake; drinks/week
Rel
ativ
e ri
sk
< 1% wine1-15% wine16-30% wine31-50% wine> 50% wine
Alcohol, wine and alcoholic cirrhosis
P < 0.05
.Becker U et al., Hepatology 2002
0
1
2
3
4
5
6
0 1-6 7-21 >21Alcohol intake, drinks per week
Rel
ativ
e ri
sk o
f up
per
dige
stiv
e tr
act c
ance
r
0
1 to 30
> 30
Type of alcohol and upper digestive tract cancer
Grønbæk et al. BMJ 1998
Wine, %
Differences in morbidity and mortality
among drinkers of beer, wine and spirits
Components? Flavonoids, polyphenols, nitrosamines
Confounders?Lifestyle factors, social class, diet
Income
0,40
0,50
0,60
0,70
0,80
0,90
1,00
1,10
Never Monthly Weekly 1-2 Drinksdaily
> 2 Drinksdaily
Wine consumption
Re
lati
ve
mo
rta
lity
ris
k
Low Medium High
Nielsen et al. J Int Med 2004;255:280-8
Wine Intake, Social Status and MortalityCopenhagen City Heart Study
Diet, Cancer, and Health Study, Denmark, 1996
Alcoholic beverage preference
Fruit Fish Vegetables Salad No fats on bread
Olive oil for cooking
Wine
1 1 1 1 1 1
Beer 0.66 0.69 0.56 0.42 0.50 0.40
Spirits 0.98 0.84 0.65 0.51 0.80 0.54
Odds ratios for having an intake above the median of different foods according to preferred alcoholic beverage
Tjønneland et al. Am J Clin Nutr 1999
Drinking pattern:Meal related alcohol intakeType of alcoholBinge vs steady intake
Factors influencing the association between alcohol and cardiovascular disease
Drinking pattern:
Binge vs steady intake
Factors influencing the association between alcohol and cardiovascular disease
- and all-cause mortality
Drinking pattern and CVD
Frequency of drinking Alcohol intake / drinking day
Days / week <10.0 g 10.0-29.9 g 30.0 g
<1 1.00 (ref)
1-2 0.85
(0.67-1.08)
0.93
(0.78-1.10)
0.84
(0.70-1.02)
3-4 0.63
(0.33-1.19)
0.67
(0.55-0.83)
0.71
(0.54-0.93)
5-7 0.68
(0.33-1.37)
0.68
(0.57-0.82)
0.63
(0.52-0.76)
Mukamal et al., N Engl J Med 2003
Drinking pattern and CHD mortality
McElduff , BMJ 1997
Days per week
Don’t drink Rarely < 1 1 or 2 3 or 4 5 or 6 Daily
Drinks per day
Don’t drink 1.00
1 to 2 1.89 0.53 0.64 0.43 0.31 0.91
3 to 4 1.36 0.43 0.63 0.43 0.31 0.81
5 to 6 0.94 1.04 0.82 0.47 0.40 0.73
>9 1.57 1.58 0.89 0.86 1.43
Cancer, Diet and Health StudyN=57.000 1996-2001
Alcohol intake, drinks per week
1 to 6 7 to 13 14 to 21 More than 21
Characteristics* Frequent Non-frequent
Frequent Non-frequent
Frequent Non-frequent
Frequent Non-frequent
Subjects (number) 9,305 11,298 12,090 967 5,951 171 171 117
Sex (% men) 37 33 54 57 53 61 61 72
Alcohol intake (median drinks per week)
5.2 3.0 9.4 8.7 18.3 18.1 18.1 26.4
Age (mean years) 55 56 56 56 55 57 57 57
Alcohol drinking pattern and mortality
Men Women
0
1
2
3
0 <1 1-6 7-13 14-20 >21 0 <1 1-6 7-13 14+
Drinks per week
Mo
rtal
ity
Abstainers
Binge
Steady
Tolstrup et al, Addiction 2003
More evidence ?
Alcohol – positive and negative ’effects’
More evidence ?
Intervention study?
Alcohol – positive and negative ’effects’
0,2
0,4
0,6
0,8
1
1,2
1,4
1,6
1,8
0 <1 1 2 3 4 5 6+
Alcohol, drinks per day
Rel
ativ
e m
orta
lity
What will changes in alcohol intake mean for subsequent mortality?
0,2
0,4
0,6
0,8
1
1,2
1,4
1,6
1,8
0 <1 1 2 3 4 5 6+
Alcohol, drinks per day
Rel
ativ
e m
orta
lity
Changes in alcohol intake and mortality?
0,4
0,6
0,8
1
1,2
1,4
1,6
1,8
0 <1 1 2 3 4 5 6+
Alkohol, genstande per dag
Død
elig
hed
Changes in alcohol intake and mortality?
0,4
0,6
0,8
1
1,2
1,4
1,6
1,8
0 <1 1 2 3 4 5 6+
Alkohol, genstande per dag
Død
elig
hed
Changes in alcohol intake and mortality
Grønbæk et al., Epidemiology 2004;15(2):222-8
Alcohol intake, first examination, drinks per week
Alcohol intake, second examination, drinks per week
Number of subjects < 1 1-6 7-13 > 13
< 1 2,269 653 131 45
1-6 1,435 2,670 829 235
7-13 263 996 1,238 718
> 13 137 343 674 2,018
Copenhagen Centre for Prospective Population Studies
N = 30,630 participants
Changes in alcohol intake and mortality
Grønbæk et al., Epidemiology 2004;15(2):222-8
Alcohol intake, first examination, drinks per week
Alcohol intake, second examination, drinks per week
Number of subjects < 1 1-6 7-13 > 13
< 1 2,269 653 131 45
1-6 1,435 2,670 829 235
7-13 263 996 1,238 718
> 13 137 343 674 2,018
Copenhagen Centre for Prospective Population Studies
N = 30,630 participants
Changes in alcohol intake and mortality
Stable intake
0,6
0,8
1
1,2
1,4
1,6
1,8
2
<1 1-6 7-13 >13
Drinks per week
Mor
tali
ty f
rom
all
cau
ses
Grønbæk et al.,Epidemiology 2004;15(2):222-8
Changes in alcohol intake and CHD mortality
Stable intake
0,6
0,8
1
1,2
1,4
1,6
1,8
2
<1 1-6 7-13 >13
Drinks per week
Mor
tali
ty f
rom
cor
onar
y he
art
dise
ase
Grønbæk et al.,Epidemiology 2004;15(2):222-8
Changes in alcohol intake and mortality
Grønbæk et al., Epidemiology 2004;15(2):222-8
Alcohol intake at first examination
Alcohol intake at second examination
< 1 1-6 7-13 > 13
< 1 1.00 † 0.94 (0.78-1.14) 1.04 (0.76-1.43) 1.26 (0.75-2.11)
1-6 1.21 (1.04-1.41) 1.00 † 1.00 (0.81-1.23) 1.21 (0.88-1.67)
7-13 1.39 (1.09-1.77) 0.91 (0.75-1.11) 1.00 † 1.21 (0.99-1.49)
> 13 1.44 (1.10-1.88) 1.01 (0.82-1.25) 0.89 (0.75-1.06) 1.00 †
Changes in alcohol intake and CHD mortality
Grønbæk et al., Epidemiology 2004;15(2):222-8
Alcohol intake at first examination
Alcohol intake at second examination
< 1 1-6 7-13 > 13
< 1 1.00 † 0.71 (0.44-1.14) 0.92 (0.45-1.90) 0.56 (0.14-2.30)
1-6 1.40 (1.00-1.95) 1.00 † 0.79 (0.48-1.30) 0.38 (0.12-1.20)
7-13 1.46 (0.86-2.45) 0.76 (0.49-1.17) 1.00 † 1.09 (0.70-1.71)
> 13 1.42 (0.71-2.82) 1.15 (0.70-1.87) 1.05 (0.70-1.56) 1.00 †
Summary
Alcohol and morbidity/mortality
Lower risk among light drinkers of any alcohol
Possibly interaction with:Age, sex and genetics factors
Drinking pattern: Beer, wine, spiritsBinge vs steady drinking