Abstract
Alcohol is used all over the world and in most Western societies,
the average intake is high. Alcohol is associated with more
than 60 diseases and globally, 4% of all deaths are attributable
to alcohol.
The aim of the present thesis is to study associations between
alcohol intake and risk of coronary heart disease (CHD),
atrial fibrillation, liver cirrhosis and pancreatitis, and more
specifically, to review the data for differential effects of alcohol
according to modifying factors on these diseases.
The thesis is based on the results from 10 epidemiological
studies, conducted in the Copenhagen City Heart Study, the
Diet, Cancer and Health Study and the Pooling Project of Diet
and Coronary Disease. In all study cohorts, a lower risk of CHD
was observed in light and moderate alcohol drinkers. In the
Copenhagen City Heart Study, we also found that increasing
alcohol intake was associated with increasing HDL cholesterol
and non-fasting triglycerides, higher systolic and diastolic
blood pressure and decreasing fibrinogen. In contrast, ADH1B
and ADH1C genotypes were not associated with risk of CHD or
with any of the cardiovascular biomarkers, and there was no
indication that associations between alcohol intake and CHD
and between alcohol intake and biomarkers were modified by
genotypes. The finding that ADH genotypes are not modifying
the association between alcohol and CHD was confirmed in the
Diet, Cancer and Health Study.
In the Pooling Project of Diet and Coronary Disease, we
found that the association between alcohol and relative risk of
CHD was similar in young adults (39-50 years), middle-aged
(50-60 years) and older individuals (60+ years). However,
since the incidence of CHD is low in young adults, the incidence
rate difference between nondrinkers and moderate
drinkers was much smaller in young adults than in older individuals,
hence, for young adults, the absolute beneficial effect
of alcohol is small.
Alcohol has differential effects on the risk of mortality and
CHD according to drinking pattern. In the Diet, Cancer and
Health Study, we found that for the same weekly amount of
alcohol intake, a non-frequent intake implied a higher risk of
- 15 -
death than a frequent one. For CHD, drinking frequency may
be the primary determinant of the inverse association between
alcohol intake and CHD: The risk of CHD was lower
among men who drank alcohol on more days of the week,
compared to men who drank alcohol on fewer days of the
week, independent of the total weekly amount of alcohol intake.
The risk of atrial fibrillation according to alcohol intake
seems to be threshold-shaped; In the Copenhagen City Heart
Study, no increased risk was observed among light to moderate
drinkers and an increased risk only among individuals
drinking >35 drinks per week.
Also in the Copenhagen City Heart Study, the risk of liver
cirrhosis was strongly associated with increasing alcohol
intake. Further, we found that increasing alcohol intake associated
with biomarkers for liver damage (alanine aminotransferase,
albumin, alkaline phosphatase, bilirubin, coagulation
factors II, VII and X, -glutamyl transpeptidase and mean erythrocyte
volume). In contrast, ADH1B and ADH1C genotypes
were not associated with a risk of liver cirrhosis or with any of
these biomarkers, and there was no indication that associations
between alcohol intake and liver cirrhosis and between
alcohol intake and biomarkers were modified by genotypes.
Finally, we observed that alcohol intake was associated
with an increased risk of pancreatitis. Smoking was also associated
with an increased risk of pancreatitis, which was independent
of alcohol and of gallstone disease; two risk factors
suggested as being the main causes of pancreatitis.
In conclusion, the results show that the association between
alcohol and CHD is independent of genetic variation in
alcohol-degrading enzymes. The alcohol drinking pattern is
independently associated with risk of coronary heart disease
and all-cause mortality. The beneficial effect of alcohol on CHD
is observed among both young adults, middle-aged and elderly,
but the magnitude of the absolute beneficial effect is least
among the young adults. Both alcohol and smoking are associated
with increased risk of pancreatitis. These results are
important for future studies of the biological effects of alcohol
on health and for public guidelines on alcohol.
the average intake is high. Alcohol is associated with more
than 60 diseases and globally, 4% of all deaths are attributable
to alcohol.
The aim of the present thesis is to study associations between
alcohol intake and risk of coronary heart disease (CHD),
atrial fibrillation, liver cirrhosis and pancreatitis, and more
specifically, to review the data for differential effects of alcohol
according to modifying factors on these diseases.
The thesis is based on the results from 10 epidemiological
studies, conducted in the Copenhagen City Heart Study, the
Diet, Cancer and Health Study and the Pooling Project of Diet
and Coronary Disease. In all study cohorts, a lower risk of CHD
was observed in light and moderate alcohol drinkers. In the
Copenhagen City Heart Study, we also found that increasing
alcohol intake was associated with increasing HDL cholesterol
and non-fasting triglycerides, higher systolic and diastolic
blood pressure and decreasing fibrinogen. In contrast, ADH1B
and ADH1C genotypes were not associated with risk of CHD or
with any of the cardiovascular biomarkers, and there was no
indication that associations between alcohol intake and CHD
and between alcohol intake and biomarkers were modified by
genotypes. The finding that ADH genotypes are not modifying
the association between alcohol and CHD was confirmed in the
Diet, Cancer and Health Study.
In the Pooling Project of Diet and Coronary Disease, we
found that the association between alcohol and relative risk of
CHD was similar in young adults (39-50 years), middle-aged
(50-60 years) and older individuals (60+ years). However,
since the incidence of CHD is low in young adults, the incidence
rate difference between nondrinkers and moderate
drinkers was much smaller in young adults than in older individuals,
hence, for young adults, the absolute beneficial effect
of alcohol is small.
Alcohol has differential effects on the risk of mortality and
CHD according to drinking pattern. In the Diet, Cancer and
Health Study, we found that for the same weekly amount of
alcohol intake, a non-frequent intake implied a higher risk of
- 15 -
death than a frequent one. For CHD, drinking frequency may
be the primary determinant of the inverse association between
alcohol intake and CHD: The risk of CHD was lower
among men who drank alcohol on more days of the week,
compared to men who drank alcohol on fewer days of the
week, independent of the total weekly amount of alcohol intake.
The risk of atrial fibrillation according to alcohol intake
seems to be threshold-shaped; In the Copenhagen City Heart
Study, no increased risk was observed among light to moderate
drinkers and an increased risk only among individuals
drinking >35 drinks per week.
Also in the Copenhagen City Heart Study, the risk of liver
cirrhosis was strongly associated with increasing alcohol
intake. Further, we found that increasing alcohol intake associated
with biomarkers for liver damage (alanine aminotransferase,
albumin, alkaline phosphatase, bilirubin, coagulation
factors II, VII and X, -glutamyl transpeptidase and mean erythrocyte
volume). In contrast, ADH1B and ADH1C genotypes
were not associated with a risk of liver cirrhosis or with any of
these biomarkers, and there was no indication that associations
between alcohol intake and liver cirrhosis and between
alcohol intake and biomarkers were modified by genotypes.
Finally, we observed that alcohol intake was associated
with an increased risk of pancreatitis. Smoking was also associated
with an increased risk of pancreatitis, which was independent
of alcohol and of gallstone disease; two risk factors
suggested as being the main causes of pancreatitis.
In conclusion, the results show that the association between
alcohol and CHD is independent of genetic variation in
alcohol-degrading enzymes. The alcohol drinking pattern is
independently associated with risk of coronary heart disease
and all-cause mortality. The beneficial effect of alcohol on CHD
is observed among both young adults, middle-aged and elderly,
but the magnitude of the absolute beneficial effect is least
among the young adults. Both alcohol and smoking are associated
with increased risk of pancreatitis. These results are
important for future studies of the biological effects of alcohol
on health and for public guidelines on alcohol.
| Original language | Danish |
|---|---|
| Publisher | |
| Publication status | Published - 2011 |