Women’s health in the Lund area (WHILA) - Alcohol consumption and all-cause mortality among women – a 17 year follow-up study
Midlöv et al. BMC Public Health
Women's health in the Lund area (WHILA) - Alcohol consumption and all-cause mortality among women - a 17 year follow-up study
Patrik Midlöv 0
Susanna Calling 0
Ashfaque A. Memon 0
Jan Sundquist 0
Kristina Sundquist 0
Sven-Erik Johansson 0
0 Center for Primary Health Care Research, Department of Clinical Sciences, Lund University , Jan Waldenströms gata 35, 205 02 Malmö , Sweden
Background: Alcohol consumption contributes to many negative health consequences and is a risk factor for death. Some previous studies however suggest a J-shaped relationship between the level of alcohol consumption and all-cause mortality. These findings have in part been suggested to be due to confounders. The aim of our study was to analyze the relationship between self-reported alcohol intake and all-cause mortality in women, adjusted for sociodemographic, lifestyle factors and diseases such as diabetes and previous ischemic heart disease. Methods: All women aged 50-59 years (born between 1935 and 1945) that lived in any of the five municipalities in southern Sweden were invited to participate in a health survey. From December 1995 to February 2000 a total of 6916 women (out of 10,766, the total population of women in 1995) underwent a physical examination and answered a questionnaire. We followed the women from the day of screening until death, or if no event occurred until May 31st 2015. Mortality was ascertained through the national cause-of-death register. Results: In this study a total of 6353 women were included. Alcohol consumption showed a J-formed relationship with mortality, when adjusted for education, marital status, smoking, BMI, physical fitness, diabetes and ischemic heart disease before screening. Non consumption of alcohol was associated with increased mortality as well as higher levels of consumption, from 12 grams per day and upwards. Conclusions: There was a clear J-shaped relation between the amount of alcohol consumption and all-cause mortality even after controlling for sociodemography, lifestyle factors and diseases such as diabetes and previous ischemic heart disease. The observed protective effect of light drinking (1-12 grams/day) could thus not be attributed to any of these known confounders.
Alcohol; Mortality; Women; J-shaped
Alcohol consumption contributes to a wide range of
negative acute and chronic health consequences and is one of
the major factors for burden of disease [
]. The net burden
caused by alcohol consumption in the European Union in
recent years has been estimated to be one in seven deaths
in males and one in 14 deaths in females [
]. There are
different mechanisms by which alcohol affects the risk of
death. Changes in lipoproteins such as increasing HDL
cholesterol and apolipoprotein A1, as well as an association
between alcohol intake and a favourable haemostatic
profile have been suggested [
]. Another possible mechanism
is the U-shaped association between alcohol consumption
and fibrinogen concentrations [
Alcohol consumption does not only increase the risk
for many diseases but is also a risk factor for death by
external causes i.e. injuries [
]. In Sweden, alcohol abuse
increases the relative risk of death by accidents by 14.9
in women and by 9.1 in men [
There are however disparities in the connection
between mortality and the use of alcohol. Previous studies
have suggested a J-shaped or even U-shaped
relationship between the level of alcohol consumption and
allcause mortality [
]. The increased risk for abstainers
has been due to a greater possibility of cardiovascular
] including stroke [
]. However, other
studies have questioned the J-shaped relationship
between the level of alcohol consumption and all-cause
mortality and suggested it to be attributable to weak
adjustment for confounders or misclassification bias
due to mixing former drinkers with lifelong abstainers
]. Possible confounding factors such as marital status
], education [
], physical activity [
] and obesity [
may affect these associations. Diabetes could be another
potential confounding factor since moderate alcohol
consumption has been reported to be inversely associated
with the risk of diabetes, whereas high alcohol
consumption could be associated with a higher risk [
in women [
]. It has been suggested that women have an
increased risk for all-cause mortality due to alcohol
consumption compared with men [
]. There is a need for
more studies on women’s alcohol consumption and effect
In a previous study from the same population, which
had a shorter follow-up time, (9 years instead of 17 years)
alcohol abstainers had no increased mortality after
adjusting for socio-demographic and health predictors [
The main aim of the present study was to analyze the
relationship between self-reported alcohol intake and
all-cause mortality in women, also adjusted for
sociodemographic, lifestyle factors and diseases such as diabetes
and previous ischemic heart disease.
Data for the present study were retrieved from the
Women’s Health in Lund Area (WHILA) study [
women aged 50–59 years (born between 1935 and 1945)
that lived in any of the five municipalities in southern
Sweden were invited to participate in a health survey.
From December 1995 to February 2000 a total of 6916
women (out of 10,766, the total population of women in
1995) underwent a physical examination and answered a
questionnaire. Thus, the participation rate was 64.2 %.
The questionnaire that was distributed to all participants
has been described in a previous Swedish study from
]. After providing written consent the
participants spent up to 2 h to answer the questionnaire, which
included questions about alcohol consumption,
sociodemographic data and health. If the participants had any
queries they could ask a nurse. There was no financial
reimbursement for participation.
We followed the women from the day of screening
until death, or if no event occurred until May 31st 2015.
Mortality was ascertained through the national
All-cause mortality: All deaths recorded from baseline
until end of the follow-up on May 31st 2015. In total there
were 579 deaths and on average 17 years follow-up.
All explanatory variables, except age, weight and height,
ischemic heart disease (IHD), and diabetes were
selfreported in the questionnaire. Age was taken from the
population register, while weight, height, and diabetes
were obtained from a clinical investigation, while IHD
was taken from the Swedish National Patient Registry.
Age, age at screening, Age centred round its mean
Education; Educational level was categorized into low
(≤12 years) and middle/high (>12 years of schooling).
Partnership status was dichotomized into married vs.
Body Mass Index (BMI; (weight (kg)/height2 (m)) was
categorized into underweight (<18.5), normal weight
(18.5–24.9), overweight (25–29.9) and obese (≥ 30).
Alcohol consumption (grams of alcohol per day)
comprised of three groups: none, 0.1–11.9, and ≥12.0 (12
grams of pure alcohol equals one drink). Alcohol
consumption was assessed by the following question: ‘How
much alcohol do you drink in an ordinary week?’ and to
report the quantity of glass/bottles (specified in
centilitres) of beer, wine and spirits respectively, or the option
‘no alcohol’. Each participant’s total consumption of
alcohol was converted into grams of alcohol for beer,
wine and spirits separately and then divided into total
grams of alcohol per day. Non-drinkers were identified
by the question: Do you on the whole drink any alcohol:
Yes/No, where No is classified as non-drinkers.
The women were divided into three groups:
– 0 g Women who did not drink any alcohol in an
012345 10 15 20 25 30 35 40 45 50 55 60
Alcohol intake, grams per day
Fig. 1 The Hazard ratio of all-cause mortality by alcohol consumption
(grams per day), adjusted for age
– 0.1-11.9 g alcohol per day.
– ≥12 g alcohol per day.
The variable is also treated as continuous in the
models. We used restricted cubic splines in order to
show the hazard ratios over the entire scale of alcohol
Physical fitness (based on a 7-level ordinal scale
ranging from very poor to very good) was dichotomized:
Poor (1–3) and Middle/Good (4–7).
Ischemic heart disease (IHD) before screening was
dichotomized (obtained from the Swedish National
Patient Registry diagnoses: 410–414/I20–I24): Yes/No.
Diabetes (obtained from the clinical investigation):
In order to compensate for missing we weighted data by
Ni/nresponders per 1-year age-group (50–59). The response
rate varied in the different age-groups between 58.9 %
(youngest) and 66.7 % (oldest), on average 64.2 %.
We used Cox proportional hazard model to analyze
the relationship between alcohol consumption and
allcause mortality, adjusted for potential confounders. We
had no specific hypotheses for interactions, therefore we
tested the first order interactions for all variables except
diabetes and ischemic heart disease, in total 21
interactions vs. alpha = (0.05/21) = 0.0024.
To show the hazard ratios of alcohol consumption
over the entire scale we used restricted cubic splines by
including alcohol as a continuous variable in the models.
This study was approved by the ethics committee in
Lund (approval no. 174–95 and 2011/494). Participation
in the study was based on informed consent.
The participants were on average 56 years of age at the
screening. In this study only 6353 women were included,
mostly due to missing in alcohol consumption. A total
of 563 women were excluded (Table 1).
Alcohol consumption showed a J-formed relationship
with mortality, when adjusted for age (Fig. 1). This
relationship remained after adjusting for education, marital
status, smoking, BMI, physical fitness, diabetes, and
ischemic heart disease before screening (Fig. 2). There
were fewer participants with middle/high educational level
and more non-smokers among non-drinkers (Table 2).
Diabetes and obesity were also more common among
non-drinkers (Table 2).
Non consumption of alcohol was associated with
increased mortality, as well as higher levels of
consumption, from 12 grams per day and upwards.
Poor education, single marital status, smoking, obesity,
poor physical fitness, diabetes, and ischemic heart
disease were all associated with higher mortality (Table 3).
For example, women who did not consume alcohol
had a similar age-adjusted hazard ratio of all-cause
mortality as women with a high consumption of alcohol; HR
1.61 (1.34–1.92) and 1.59 (1.25–2.01) respectively.
Socioeconomic factors, such as low educational status or living
alone, had similar increased risks of all-cause mortality
with hazard ratios of 1.50 and 1.50 respectively, adjusted
for age. Women that were underweight had the highest
hazard ratio of all-cause mortality; 3.41 (2.11–5.51).
In Table 4 we adjusted for all included variables. In
this model we categorized alcohol consumption and lost
quite a lot of information compared with the figure
where the model was based on continuous alcohol
consumption. The loss of information was especially large
among heavy drinkers. The hazard ratio for women with
no alcohol consumption decreased from 1.61 to 1.36.
For women with high alcohol consumption the risk
decreased from 1.59 to 1.49 after adjusting for
education, marital status, fitness, smoking, BMI, diabetes, and
ischemic heart disease. All other hazard ratios decreased
but remained significant, with the exception of obesity
as that was no longer significant.
In this prospective cohort study of middle-aged women,
with over 17 years of follow-up, there was a clear J-shaped
relation between amount of alcohol consumption and
allcause mortality even after controlling for sociodemography,
lifestyle factors and diseases such as diabetes and previous
ischemic heart disease. The observed protective effect of
light drinking (1–12 grams/day) could thus not be
attributed to any of these known confounders.
The J-shaped mortality curve observed in this study
among light to moderate drinkers is consistent with
previous studies [
]. The reasons are not clear but there
remains the possibility that the consumption of small
amounts of alcohol may protect against the development
of cardiovascular disease [
10, 22, 23
]. This might be due
to the effects of alcohol on cardiovascular biomarkers
e.g. high-density lipoprotein cholesterol, adiponectin,
fibrinogen and the effect on haemostatic factors [
It has also been shown that moderate alcohol
consumption is associated with a lower risk of mortality and diabetes
]. One plausible mechanism that might explain this
association is the enhanced insulin sensitivity in
light-tomoderate alcohol consumers [
], but the reasons behind
this remain unclear. It is also worth mentioning, although
we could not control for this, that the lower mortality risk
in moderate drinkers could be confounded by better
developed social networks found among moderate drinkers.
High educational level was least common among
abstainers. This association has been reported previously
]. The association between educational level and
mortality might be due to health behaviours [
association between alcohol consumption and BMI was
weak in our study. This is in line with previous results,
which indicated that the precise effect of alcohol on
body weight remains to be determined .
The findings in our study are especially important
since women might have an increased risk of
alcoholrelated mortality compared with men [
]. There is a
need for interventions to decrease alcohol consumption
among women with moderate to heavy alcohol intake.
A discussion of alcohol consumption should form a
part of preventive counselling but all possible effects of
alcohol use must be considered. The amount of alcohol
intake where the protective effects exceed the adverse
effects is unclear. Alcohol drinking is associated with
many health problems. Increased consumption of
alcohol should not be recommended as a prevention of
mortality (or cardiovascular disease). Any advice regarding
the consumption of alcohol should be adjusted to factor
in the risks and potential benefits for each individual
patient. One should bear in mind that there is no
control mechanism for alcohol purchase as e.g. for
prescription of drugs. Alcohol is available and when
recommending to increasing alcohol intake there is a
risk for consumption levels that increases mortality.
Strengths and limitations
The strengths of the present study are the prospective
design and the large sample of women drawn from the
general population. We have a long follow-up period and the
data has been adjusted for several possible confounders. By
using restricted cubic splines we showed the hazard ratios
of the entire scale of alcohol consumption with adjustment
for all other variables, without any loss of information.
Epidemiological studies have obvious limitations and
the results must be interpreted cautiously. Abstainers
may differ from drinkers in aspects that we have not
adjusted our model for. There might be confounders that
we are not aware of. In addition, some of the abstainers
may in fact not be complete teetotallers. In this study we
could not separate participants who used alcohol on a
less than weekly from those who were total abstainers.
Another problem of using baseline questionnaires in
follow-up studies is that alcohol consumption may change
over time. We assume that the level of alcohol
consumption at baseline is an accurate estimate of exposure
throughout several years. In our study it is not possible to
differentiate between former drinkers and lifelong
There might be a bias in the self-reporting of alcohol
]. The possibility of higher rate of
under-reporting of consumption in heavy drinkers cannot
be ruled out. Self-reported data can be influenced by
several factors, including social context and cultural norms,
people may alter their response according to perceived
social desirability . It has however been shown that
self-reported alcohol consumption can be reliable [
There is also a possibility that non-responders are
different from the responders and non-responders may have an
increased hazard ratio of alcohol-related mortality [
When it comes to IHD and diabetes we cannot rule
out the possibility that these diseases may have occurred
after inclusion in the study. In that case we do not know
about these diagnoses, we only have data at baseline.
In conclusion, no alcohol consumption or alcohol
consumption of more than 12 g per day (seven drinks per
week) were associated with increased mortality in women.
This study underlines the need for further studies
regarding mechanisms of the effect of alcohol on mortality.
The authors declare that they have no competing interests.
PM, SC, AM, JS, KS, SJ worked on conception of the study; SJ wrote the initial
statistical analysis plan; PM, SC, AM, JS, and KS contributed to the statistical
analysis plan; SJ analysed the data; PM, SC, AM, JS, KS contributed to the
analysis and interpretation of the data; PM drafted the paper; SC, AM, JS, KS,
SJ worked on further drafting and revising the paper critically. All authors
read and approved the final manuscript.
This work was supported by ALF funding from Region Skåne awarded to
Patrik Midlöv, Jan Sundquist and Kristina Sundquist as well as The Swedish
Research Council for Health, Working Life and Welfare (In Swedish: Forte;
Reg.nr: 2013–1836) to Kristina Sundquist. Research reported in this
publication was also supported by the National Institute On Alcohol Abuse
And Alcoholism of the National Institutes of Health under Award Number
R01AA023534. The content is solely the responsibility of the authors and
does not necessarily represent the official views of the National Institutes of
We are indebted to Patrick Reilly for his expertise and invaluable advice in
editing the manuscript.
Submit your next manuscript to BioMed Central
and we will help you at every step:
1. Rehm J , Baliunas D , Borges GL , Graham K , Irving H , Kehoe T , et al. The relation between different dimensions of alcohol consumption and burden of disease: an overview . Addiction . 2010 ; 105 ( 5 ): 817 - 43 .
2. Rehm J , Shield KD , Gmel G , Rehm MX , Frick U . Modeling the impact of alcohol dependence on mortality burden and the effect of available treatment interventions in the European Union . Eur Neuropsychopharmacol . 2013 ; 23 ( 2 ): 89 - 97 .
3. Rimm EB , Williams P , Fosher K , Criqui M , Stampfer MJ . Moderate alcohol intake and lower risk of coronary heart disease: meta-analysis of effects on lipids and haemostatic factors . BMJ . 1999 ; 319 ( 7224 ): 1523 - 8 .
4. Mennen LI , Balkau B , Vol S , Caces E , Eschwege E. Fibrinogen : a possible link between alcohol consumption and cardiovascular disease? DESIR study group . Arterioscler Thromb Vasc Biol . 1999 ; 19 ( 4 ): 887 - 92 .
5. Guitart AM , Espelt A , Castellano Y , Suelves JM , Villalbi JR , Brugal MT . Injury-related mortality over 12 years in a cohort of patients with alcohol Use disorders: higher mortality among young people and women . Alcohol Clin Exp Res . 2015 ; 39 ( 7 ): 1158 - 65 .
6. Crump C , Sundquist K , Winkleby MA , Sundquist J . Mental disorders and risk of accidental death . Br J Psychiatry . 2013 ; 203 ( 3 ): 297 - 302 .
7. Di Castelnuovo A , Costanzo S , Bagnardi V , Donati MB , Iacoviello L , de Gaetano G. Alcohol dosing and total mortality in men and women: an updated meta-analysis of 34 prospective studies . Arch Intern Med . 2006 ; 166 ( 22 ): 2437 - 45 .
8. Rehm J , Gmel G , Sempos CT , Trevisan M . Alcohol-related morbidity and mortality . Alcohol Res Health . 2003 ; 27 ( 1 ): 39 - 51 .
9. O 'Keefe JH , Bybee KA , Lavie CJ . Alcohol and cardiovascular health: the razorsharp double-edged sword . J Am Coll Cardiol . 2007 ; 50 ( 11 ): 1009 - 14 .
10. Roerecke M , Rehm J . Alcohol consumption, drinking patterns, and ischemic heart disease: a narrative review of meta-analyses and a systematic review and meta-analysis of the impact of heavy drinking occasions on risk for moderate drinkers . BMC Med . 2014 ; 12 : 182 .
11. Patra J , Taylor B , Irving H , Roerecke M , Baliunas D , Mohapatra S , et al. Alcohol consumption and the risk of morbidity and mortality for different stroke types-a systematic review and meta-analysis . BMC Public Health . 2010 ; 10 : 258 .
12. Knott CS , Coombs N , Stamatakis E , Biddulph JP . All cause mortality and the case for age specific alcohol consumption guidelines: pooled analyses of up to 10 population based cohorts . BMJ . 2015 ; 350 : h384 .
13. Prescott CA , Kendler KS . Associations between marital status and alcohol consumption in a longitudinal study of female twins . J Stud Alcohol . 2001 ; 62 ( 5 ): 589 - 604 .
14. van Oort FV , van Lenthe FJ , Mackenbach JP . Material, psychosocial, and behavioural factors in the explanation of educational inequalities in mortality in The Netherlands . J Epidemiol Community Health . 2005 ; 59 ( 3 ): 214 - 20 .
15. Pedersen JO , Heitmann BL , Schnohr P , Gronbaek M. The combined influence of leisure-time physical activity and weekly alcohol intake on fatal ischaemic heart disease and all-cause mortality . Eur Heart J . 2008 ; 29 ( 2 ): 204 - 12 .
16. Bazzano LA , Gu D , Reynolds K , Chen J , Wu X , Chen CS , et al. Alcohol consumption and risk of coronary heart disease among Chinese men . Int J Cardiol . 2009 ; 135 ( 1 ): 78 - 85 .
17. Baliunas DO , Taylor BJ , Irving H , Roerecke M , Patra J , Mohapatra S , et al. Alcohol as a risk factor for type 2 diabetes: a systematic review and metaanalysis . Diabetes Care . 2009 ; 32 ( 11 ): 2123 - 32 .
18. Cullmann M , Hilding A , Ostenson CG . Alcohol consumption and risk of prediabetes and type 2 diabetes development in a Swedish population . Diabet Med . 2012 ; 29 ( 4 ): 441 - 52 .
19. Wang C , Xue H , Wang Q , Hao Y , Li D , Gu D , et al. Effect of drinking on allcause mortality in women compared with men: a meta-analysis . J Womens Health (Larchmt) . 2014 ; 23 ( 5 ): 373 - 81 .
20. Rundberg J , Nilsson PM , Samsioe G , Ojehagen A . Alcohol use and early mortality in Swedish middle-aged women: nine-year follow-up of the Women's health in Lund area study . Scand J Public Health . 2014 ; 42 ( 4 ): 344 - 8 .
21. Cederfjall J , Lidfeldt J , Nerbrand C , Samsioe G , Ojehagen A . Alcohol consumption among middle-aged women: a population-based study of Swedish women. The Women's health in Lund area (WHILA) study . Eur Addict Res . 2004 ; 10 ( 1 ): 15 - 21 .
22. Snow WM , Murray R , Ekuma O , Tyas SL , Barnes GE . Alcohol use and cardiovascular health outcomes: a comparison across age and gender in the Winnipeg health and drinking survey cohort . Age Ageing . 2009 ; 38 ( 2 ): 206 - 12 .
23. Kabagambe EK , Baylin A , Ruiz-Narvaez E , Rimm EB , Campos H . Alcohol intake, drinking patterns, and risk of nonfatal acute myocardial infarction in Costa Rica . Am J Clin Nutr . 2005 ; 82 ( 6 ): 1336 - 45 .
24. Brien SE , Ronksley PE , Turner BJ , Mukamal KJ , Ghali WA . Effect of alcohol consumption on biological markers associated with risk of coronary heart disease: systematic review and meta-analysis of interventional studies . BMJ . 2011 ; 342 : d636 .
25. Rubin R , Rand ML . Alcohol and platelet function . Alcohol Clin Exp Res . 1994 ; 18 ( 1 ): 105 - 10 .
26. de Vegt F , Dekker JM , Groeneveld WJ , Nijpels G , Stehouwer CD , Bouter LM , et al. Moderate alcohol consumption is associated with lower risk for incident diabetes and mortality: the Hoorn Study . Diabetes Res Clin Pract . 2002 ; 57 ( 1 ): 53 - 60 .
27. Facchini F , Chen YD , Reaven GM . Light-to-moderate alcohol intake is associated with enhanced insulin sensitivity . Diabetes Care . 1994 ; 17 ( 2 ): 115 - 9 .
28. Johnson W , Kyvik KO , Mortensen EL , Skytthe A , Batty GD , Deary IJ . Does education confer a culture of healthy behavior? Smoking and drinking patterns in Danish twins . Am J Epidemiol . 2011 ; 173 ( 1 ): 55 - 63 .
29. Laaksonen M , Talala K , Martelin T , Rahkonen O , Roos E , Helakorpi S , et al. Health behaviours as explanations for educational level differences in cardiovascular and all-cause mortality: a follow-up of 60 000 men and women over 23 years . Eur J Public Health . 2008 ; 18 ( 1 ): 38 - 43 .
30. Schrijvers CT , Stronks K , van de Mheen HD , Mackenbach JP . Explaining educational differences in mortality: the role of behavioral and material factors . Am J Public Health . 1999 ; 89 ( 4 ): 535 - 40 .
31. Sayon-Orea C , Martinez-Gonzalez MA , Bes-Rastrollo M . Alcohol consumption and body weight: a systematic review . Nutr Rev . 2011 ; 69 ( 8 ): 419 - 31 .
32. Zheng YL , Lian F , Shi Q , Zhang C , Chen YW , Zhou YH , et al. Alcohol intake and associated risk of major cardiovascular outcomes in women compared with men: a systematic review and meta-analysis of prospective observational studies . BMC Public Health . 2015 ; 15 ( 1 ): 773 .
33. Del Boca FK , Darkes J. The validity of self-reports of alcohol consumption: state of the science and challenges for research . Addiction . 2003 ; 98 Suppl 2 : 1 - 12 .
34. Ramstedt M. How much alcohol do you buy? A comparison of self-reported alcohol purchases with actual sales . Addiction . 2010 ; 105 ( 4 ): 649 - 54 .
35. Davis CG , Thake J , Vilhena N. Social desirability biases in self-reported alcohol consumption and harms . Addict Behav . 2010 ; 35 ( 4 ): 302 - 11 .
36. Gronbaek M , Heitmann BL . Validity of self-reported intakes of wine, beer and spirits in population studies . Eur J Clin Nutr . 1996 ; 50 ( 7 ): 487 - 90 .
37. Christensen AI , Ekholm O , Gray L , Glumer C , Juel K. What is wrong with non-respondents? Alcohol-, drug- and smoking-related mortality and morbidity in a 12-year follow-up study of respondents and nonrespondents in the Danish Health and Morbidity Survey . Addiction . 2015 ; 110 ( 9 ): 1505 - 12 .