Prospective study of alcohol drinking patterns and coronary heart disease in women and men
BMJ 2006; 332 doi: https://doi.org/10.1136/bmj.38831.503113.7C (Published 25 May 2006) Cite this as: BMJ 2006;332:1244
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Dear Editor,
That the frequency of drinking is a determinant of the cardiovascular
effects studied by Tolstrup et al, suggests that reversible mechanisms are
involved. One such mechanism might be a reduction in inflammation induced
by drinking. In the study reported by Sierksma et al (1) it was observed
that two inflammation markers produced by the liver became lowered in
plasma concentration during a period of three weeks of moderate drinking.
It concerned two markers, fibrinogen and C-reactive protein (CRP), that
are very well known, established risk markers of cardiovascular events.
Possibly the most important sentence in the paper of Sierksma et al (1),
not explicitly discussed, is: “No carry-over effects were seen”. This
refers to the cross-over design of the study with one week interval
between the 3 week drinking periods of either beer or no-alcohol beer.
Apparently, the one week was sufficient for the alcohol drinking group to
return to baseline levels to start the period with no-alcohol beer. The
study is small, but is suggests clearly to pay attention to the
reversibility of this type of alcohol effects. In particular CRP has a
short half life and can react swiftly within one day. Fibrinogen is not
that dynamic. I would like to know whether drinking every day , or
stopping one or two days etc, is required to maintain or loose the anti-
inflammatory effect on dynamic variables such as CRP and would suggest to
analyse epidemiological studies from this timing perspective.
(1) Sierksma A, van der Gaag MS, Kluft C, Hendriks HF. Moderate
alcohol consumption reduces plasma C-reactive protein and fibrinogen
levels; a randomized, diet-controlled intervention study. Eur J Clin
Nutr. 2002 Nov;56(11):1130-6
Competing interests:
None declared
Competing interests: No competing interests
Editor,
We agree that uncontrolled confounding can have influenced our
results. However, if results are to be entirely explained by uncontrolled
factors, such factors must be potent risk factors and not be associated
with the factors that are already accounted for. Also, adjustment of
important risk factors such as smoking only had minor influence on the
size and precision of the risk estimates. Therefore, we do not think that
it is likely that our results can be entirely explained by uncontrolled
confounding. Further, apart from the well-documented clinically and
experimentally evidence for biological mechanisms (rise in HDL,
fibrinolysis, etc) we find it odd that the confounding-explanation-theory
only applies to CHD. A higher frequency of unhealthy behaviour among
abstainers and perhaps occasional drinkers would to our opinion imply an
increase in morbidity and mortality from other diseases as well (as for
instance, cancer).
We observed a rather strong inverse association between alcohol
intake and risk of coronary heart disease, which may be due to the fact
that the study population consisted of middle-aged men and women. This age
group is at high risk of coronary heart disease whereas among younger
individuals, no beneficial effect of alcohol can be expected.
We agree with Prof. de Courten that public health inferences about a
safe level of alcohol consumption should not be drawn from this paper
only, a point also stated in the last section of the Discussion. We do
believe, however, that a light to moderate intake overall implies the
lowest mortality.
Competing interests:
None declared
Competing interests: No competing interests
Editor,
This is a very interesting point. However, for the present study, as
also pointed out by Dr. Bhala, the influence of ethinicity is probably
minor. The study population consisted of middle-aged individuals that were
all born in Denmark in 1930-45 and are all presumed to be of Danish
ethnicity and thereby all Caucasians. Therefore, while race and ethnicity
may be an important confounder in some of the countires mentioned, it
cannot at all explain our findings of a strongly decreased risk of CHD
with increasing frequency of alcohol (in men).
Competing interests:
None declared
Competing interests: No competing interests
Dear Editor,
The prospective study of alcohol drinking patterns and coronary heart
disease
in women and men by Tolstrup J, et al. (1) suggests that moderate drinking
may lower coronary heart disease (CHD), and even more worrying: that the
trend seems to become greater the more often and higher quantities of
alcohol are consumed. Although most observational studies such as this
control for “major” CHD-associated risks, CHD is independently associated
with a great number of factors that were not addressed by this study (nor
many other studies alike). A recent paper in the Am J Prev Med (2) tried
to
estimate the impact of uncontrolled confounding looking at differences of
30
known cardiovascular disease (CVD) factors between moderate drinkers and
nondrinkers and demonstrated that 90% of them were more prevalent among
nondrinkers. In addition, among factors with multiple risk strata,
increasing
CVD risk was progressively associated with nondrinking status. There is no
reason to believe that this difference should only be limited to
abstainers, but
not apply to some extent to the whole spectrum of (reduced) drinking
behaviour – hence excluding abstainers from analyses would not remove
uncontrolled confounding from the findings.
Therefore we believe that even these results presented by Tolstrup et
al (1) of
the apparent protective effect of alcohol drinking could be due to
confounding and a limit of the study methodology.
As stated by R Jackson in an editorial to a similar observation of a
negative
relationship between alcohol and CVD, any coronary protection from light
to
moderate drinking will be very small and unlikely to outweigh the harms.
While the current study suggests that more frequent or moderate to heavy
drinking seems even more CHD-protective, any benefit will be overwhelmed
by the known harms.
To derive to a meaningful public-health message we need a more
comprehensive assessment of risk versus benefit than was presented here
such as the one recently commissioned in New Zealand (4) – and awaiting
this recommend to assume the overall health benefits of alcohol are no
greater than the harms caused.
(1) Tolstrup J, et al. Prospective study of alcohol drinking patterns
and
coronary heart disease in women and men. BMJ 2006; 332: 1244-1248
(2) Naimi TS, et al. Cardiovascular risk factors and confounders
among
nondrinking and moderate-drinking U.S. adults. Am J Prev Med 2005; 28:
369-73
(3) Alcohol and ischaemic heart disease: probably no free
lunch.(Comment).
Jackson R, et al. The Lancet 366.9501 (Dec 3, 2005): p1911(2).
(4) Connor J, et al. The burden of death, disease and disability due
to alcohol
in New Zealand. Wellington: Alcohol Advisory Council of New Zealand
occasional publication no 23, February, 2005: http://www.alac.org.nz/
Publications.aspx (accessed June 10, 2006).
Competing interests:
None declared
Competing interests: No competing interests
May 29, 2006
Tolstrup, et al, briefly address “biologically plausible mechanisms.”
Moderate amounts of alcohol suppress gluconeogenesis in the liver,
thus lowering the glucose load (total endogenous and exogenous glucose,
mostly glycogen stores - not the blood glucose level).
The desirable effects of moderate alcohol consumption result from
this reduction in glucose load as reflected in reductions in excessive
levels of glycogen storage in liver and then in consequent reductions in
VLDL production in the liver (VLDL production is triggered by a state of
overfull liver glycogen stores).
The VLDL reduction inhibits atherogenesis (VLDLs in the plasma
interact with CEPT, HDLs, and LDLs to produce small, dense atherogenic
LDLs and lower HDL levels).
The lower glucose load reduces beta cell destruction by reducing
insulin production demands (fuller glycogen stores require higher plasma
insulin to cram in new blood glucose via the glucose gradient - quite
separate from “insulin resistance”).
Note that both the mechanism of action of moderate alcohol and its
results parallel those of the diabetes drug metformin. Metformin’s
mechanism of direct action also is suppression of gluconeogenesis.
Of course, on modern diets gluconeogenesis only adds marginal amounts
of glucose while excessive glycogen levels are predominantly caused by
excessive dietary carbohydrate.
Competing interests:
None declared
Competing interests: No competing interests
The recent Danish study prospectively assessing the association
between alcohol and coronary heart disease raises many questions about a
long debated topic, but I would like to make some comments.(1)
The study has controlled for smoking and lifestyle interventions that
may influence cardiovascular risk, and has used length of school education
as a surrogate marker of socioeconomic status. However, they have not
been able to account for other recognized risk factors, such as
hypertension and hyperlipidaemia. These obviously need no introduction,
but a hitherto neglected area should be highlighted: the role of ethnicity
in both alcohol consumption and cardiovascular risk.
A recent BMJ editorial highlighted the ethnic differences in alcohol
behaviours, especially in the context of increased intake in Irish and
Sikh populations in the United Kingdom.(2) Furthermore, the long term
sequelae of ethanol intake, such as alcoholic liver cirrhosis in British
South Asians, have been previously demonstrated.(3) Cultural and
religious differences underpin this diversity and are heterogenous, and
can be illustrated by (teetotal) Muslims compared to people of other
religions, for example. Obviously, the UK has a slightly more diverse
population than Denmark, but this warrants attention.
The association between ethnicity and cardiovascular health is even
more well established. Much of the underlying pathophysiology remains
unclear, but British South Asians undoubtedly have an increased risk of
the metabolic syndrome, diabetes mellitus, atherosclerosis, ischaemic
heart disease and strokes.(4) There is also evidence of differences in
access to health care in both British and other minority communities.
Whilst recognised as an important area, in many ways, this is yet to
translate to clinical research and practice. A recent study of
cardiovascular cohort studies carried out revealed that only fifteen of 72
North American & European studies assessed non-white ethnic minority
groups.(5)
The continued research of mortality and morbidity secondary to both
alcohol and cardiovascular disease remains a priority. The undoubted
effect of ethnicity in both research and real life requires careful
consideration.
1. Tolstrup J, Jensen MK, Tjønneland A, et al. Prospective study of
alcohol drinking patterns and coronary heart disease in women and men.
BMJ 2006
2. Rao R. Alcohol misuse and ethnicity. BMJ 2006 Mar 25;332(7543):682.
3. Douds AC, Cox MA, Iqbal TH, Cooper BT. Ethnic differences in cirrhosis
of the liver in a British city: alcoholic cirrhosis in South Asian men.
Alcohol Alcsm 2003;38:148-50.
4. Chaturvedi N. Ethnic differences in cardiovascular disease. Heart
2003;89;681-686.
5. Ranganathan M, Bhopal R. Exclusion and Inclusion of Nonwhite Ethnic
Minority Groups in 72 North American and European Cardiovascular Cohort
Studies.
PLoS Med. 2006 Jan 3;3(3):e44
Competing interests:
None declared
Competing interests: No competing interests
Tolstrup and colleagues report that men and women differ with regard
to the inverse relationship between alcohol intake and coronary heart
disease: in women the amount consumed is purportedly the key determinant,
whereas among men, it is drinking frequency. This claim is based on
stratified analyses - essentially Table 3 in the paper.
This conclusion seems reasonable, but it would be strengthened if the
authors tested the difference between women and men directly. It is
important to do this: if a risk factor is significantly associated with
outcome in one group, but the association is non-significant in another
group, it does not follow that the difference between the groups is
significant. It should be easy for the authors to run a Cox model
including all study participants, where the occurrence of coronary heart
disease would be predicted by the following equation:
b1*sex + b2*amount + b3*frequency + b4*sex*amount + b5*sex*frequency
The regression coefficients b4 and b5 will test directly the
hypotheses that the effect of the amount or frequency of drinking varies
by sex.
Competing interests:
None declared
Competing interests: No competing interests
Editor,
Participants changing habits during follow up is always a concern in
longitudinal studies. However, the follow up period was 5.7 years in the
present study, which is a shorter period than seen in most other studies
and the likelihood of changing habits smaller. Participants were between
50 and 65 years of age, which is a relatively narrow age span. Age was
used as underlying the time axis in the Cox model to ensure that the
estimation procedure was based on comparisons of individuals at the same
age, that is, at the time of the incidence. In order to test the
hypothesis that participants in the light alcohol drinking categories had
cut down on alcohol in response to early symptoms, we performed
sensitivity analyses excluding the first two years of followup, which did
not change our conclusions. Furthermore, our data enable distinction
between frequent and non-frequent intake with in the same average intake
categories (please refer to Table 3). Doctors would most likely advice
patients to cut down irrespective of drinking frequency, implying that the
proposed bias is unlikely.
Janne Tolstrup and Morten Grønbæk
Competing interests:
None declared
Competing interests: No competing interests
We read with interest the article by Tolstrup et al. and we commend
them on this important and large piece of work. The study is a worthwhile
endeavour and for the most part we agree with their interpretation of the
findings.
Given that the potential implications of this paper are enormous, we
feel it is important to highlight and reaffirm some of the limitations and
challenge some of their complex methods concerning non-drinkers. The
authors state - non drinkers may include formal alcoholics and have not
clarified this key piece of information. Non-drinkers may also include
certain professions such as drivers, full time carers and nurses as well
as abstainers for religious or cultural beliefs. Similarly patients on
medications such as warfarin and older psychotrophic drugs or sedatives or
those who incur palpitations worsened by alcohol are less likely to
consume alcohol or to volunteer a history of such. Given this was a
prospective survey study - if the issue regarding alcohol consumption was
an apriori question, such key data should have been collected.
Furthermore the non-drinker group is an unignorably smaller group
then expected by chance suggesting there are important differences in
behavioural choices at play here. Since no account is documented as having
been undertaken to elucidate these baseline differences, important
confounders could not have been adjusted for in multivariate analyses.
Given this and the critical nature of this paper in terms of
influencing alcohol choice - in particular for those who are current and
lifelong non-alcohol drinkers, we would state that the authors might have
presented a more accurate picture having completely removed non-drinkers
from their analyses. By not having done this - the paper could be
misrepresented by alcohol distributors, producers and manufacturers to
state that some alcohol is better for you than none - which is a statement
which to the best of our knowledge has never been proven in a carefully
designed prospective randomised controlled trial using previous lifelong
abstainers and a non-alcoholic placebo.
Competing interests:
None declared
Competing interests: No competing interests
Association of alcohol intake with dietary and anthropometric markers of cardiovascular risk among UK female university student drinkers; results of a pilot study.
Sir,
Central adiposity is viewed as a risk factor for type 2 diabetes and
coronary heart disease (CHD). This effect is believed to be independent of
total obesity (Han et al., 1996; Zhu et al., 2002). The impact of alcohol
consumption on body fat distribution remains uncertain but research
identifies the potential importance of gender and pattern of consumption
as influential factors (Cigolini et al., 1996; Leite and Nicolosi, 2006).
Life stage may also be relevant. This pilot study investigated dietary and
anthropometric markers of cardiovascular disease in young females from a
population group (university students) in which binge drinking is often
the preferred method of alcohol consumption.
Inclusion criteria were consumption of alcohol at least once per
month and being a non-smoker. Each participant was instructed to keep a
(non-weighed) 7-day food intake diary and had her waist circumference (cm)
and BMI (kg/m2) measured. Macronutrient and alcohol intake for each
participant were derived using Compeat 5 software. In addition, responses
to questions relating to typical weekly alcohol intake and pattern of
consumption were recorded.
Among participants (n=18; mean age 22.1, SD = 2.66 years ), using the
criterion of exceeding one half of the weekly allowance of alcohol (7
units) in one session to define binge drinking, 50% binge drank during
the week of the study, four of them more than once, 39% exceeded weekly
health guidelines. Significant correlations existed between mean daily
intake of alcohol (mean =17.8, SD= 16.4g) and
(i) waist circumference (mean = 72.6, SD = 4.9cm). (Pearson correlation
coefficient, r = 0.79, p = 0.01.
(ii) BMI (mean = 22.90, SD = 2.55 kg/m2). (Pearson correlation
coefficient, r = 0.546, p = 0.05).
(iii) saturated fat intake (mean = 25.33, SD = 7.25g) (Pearson
correlation coefficient = 0.49, p=0.04).
Binge drinkers had a significantly greater waist circumference than
those who did not binge drink in the week of the study (independent t-
test; p = 0.012).
The pattern of drinking favoured by some young female students, is
associated with increased central adiposity and as a consequence may have
an impact on their risk of developing CHD in later life.
References:
Cigolini M, Targher G, Bergamo Andreis IA, Tonoli M, Filippi F, Muggeo M
& De Sandre G (1996) Moderate alcohol consumption and its relation to
visceral fat and plasma androgens in healthy women. International Journal
Of Obesity And Related Metabolic Disorders 20, 206-212.
Han TS, van Leer EM, Seidell JC & Lean ME. (1996) Waist circumference
as a screening tool for cardiovascular risk factors: evaluation of
receiver operating characteristics (ROC). Obesity Research 4, 533-547.
Zhu S, Wang Z, Heshka S, Heo M, Faith MS & Heymsfield SB (2002) Waist
circumference and obesity associated risk factors among whites in the
third National Health and Nutrition Examination survey: clinical action
thresholds. American Journal of Clinical Nutrition 76, 743-749.
Leite MLC & Nicolosi A (2006) Lifestyle correlates of anthropometric
estimates of body adiposity in an Italian middle-aged and elderly
population: a covariance analysis. International Journal of Obesity 30,
926-934.
Competing interests:
None declared
Competing interests: No competing interests