Critique 283 – Alcohol consumption patterns and mortality among older adults with health-related or socioeconomic risk factors

Authors

Ortolá, R.; Sotos-Prieto, M.; García-Esquinas, E.; Galán, I.; Rodríguez-Artalejo, F.

Citation

JAMA Network Open 2024 7(8): e2424495. doi:10.1001/jamanetworkopen.2024.24495

Author’s Abstract

Objective Alcohol consumption is a leading cause of morbidity and mortality that may be more important in older adults with socioeconomic or health-related risk factors. To examine the association of alcohol consumption patterns with 12-year mortality and its modification by health-related or socioeconomic risk factors.

Methods This prospective cohort study used data from the UK Biobank, a population-based cohort. Participants were current drinkers aged 60 years or older. Data were analysed from September 2023 to May 2024. According to their mean alcohol intake in grams per day, participants’ drinking patterns

were classified as occasional: <2.86 g/d), low risk (men: >2.86-20.00 g/d; women: >2.86-10.00 g/d), moderate risk (men: >20.00-40.00 g/d; women: >10.00-20.00 g/d) and high risk (men: >40.00 g/d; women: >20.00 g/d). Health-related risk factors were assessed with the frailty index, and socioeconomic risk factors were assessed with the Townsend deprivation index. All-cause and cause-specific mortality were obtained from death certificates held by the national registries. Analyses excluded deaths in the first 2 years of follow-up and adjusted for potential confounders, including drinking patterns and preferences.

Results A total of 135 103 participants (median [IQR] age, 64.0 [62.0-67.0] years; 67 693 [50.1%] women) were included. In the total analytical sample, compared with occasional drinking, high-risk drinking was associated with higher all-cause (hazard ratio [HR], 1.33; 95%CI, 1.24-1.42), cancer (HR, 1.39; 95%CI, 1.26-1.53), and cardiovascular (HR, 1.21; 95%CI, 1.04-1.41) mortality; moderate-risk drinking was associated with higher all-cause (HR, 1.10; 95%CI, 1.03-1.18) and cancer (HR, 1.15; 95% CI, 1.05-1.27) mortality, and low-risk drinking was associated with higher cancer mortality (HR, 1.11; 95%CI, 1.01-1.22). While no associations were found for low- or moderate-risk drinking patterns vs occasional drinking among individuals without socioeconomic or health-related risk factors, low-risk drinking was associated with higher cancer mortality (HR, 1.15; 95%CI, 1.01-1.30) and moderate-risk drinking with higher all-cause (HR, 1.10; 95%CI, 1.01-1.19) and cancer (HR, 1.19; 95%CI, 1.05-1.35) mortality among those with health-related risk factors; low-risk and moderate-risk drinking patterns were associated with higher mortality from all causes (low-risk: HR, 1.14; 95%CI, 1.01-1.28; moderate risk: HR, 1.17; 95%CI, 1.03-1.32) and cancer (low risk: HR, 1.25; 95%CI, 1.04-1.50; moderate risk: HR, 1.36; 95%CI, 1.13-1.63) among those with socioeconomic risk factors. Wine preference (>80% of alcohol from wine) and drinking with meals showed small protective associations with mortality, especially from cancer, but only in drinkers with socioeconomic or health-related risk factors and was associated with attenuating the excess mortality associated with high-, moderate- and even low-risk drinking.

Conclusions In this cohort study of older drinkers from the UK, even low-risk drinking was associated with higher mortality among older adults with health-related or socioeconomic risk factors. The attenuation of mortality observed for wine preference and drinking only during meals requires further investigation, as it may mostly reflect the effect of healthier lifestyles, slower alcohol absorption, or non-alcoholic components of beverages.

Forum Summary

It is well known that people with a low socioeconomic status experience higher levels of alcohol-related harm than people with a high socioeconomic status. The study by Ortolá et al. (2024) adds little to that but is interesting because it concerns the increasingly larger population group of older adults with complex health conditions, who pose an increasing burden on our healthcare system. This study in older UK adults by Ortolá and co-authors concluded that even low-risk drinking was associated with higher mortality among older adults with health-related or socioeconomic risk factors.

However, the study did not use the appropriate control group of non-drinkers or never drinkers in their comparison, while these groups were present in their population. Also, the authors used very limited information on drinking quantity and drinking pattern. Drinking categories were based on an estimated one-time average consumption per week and exclusion of one-time bingers and inclusion of weekend heavy drinkers. Such an assessment will have contributed to significant misclassification of drinking categories. Also, important other lifestyle factors like eating habits and body weight were not included in their models.

The Forum concludes that these limitations may well explain why this single study contrasts the vast number of previous studies showing that light to moderate alcohol consumption is associated with a reduced mortality in older adults.

Forum comments

Background

Life expectancy is increasing worldwide. Older adults and the elderly are rapidly growing groups, as population aging is much faster than in previous decades. In low- and middle-income countries, this is largely the result of large reductions in mortality at younger ages, particularly during childhood and childbirth, and from infectious diseases (Bloom, 2011). In high-income countries, continuing increases in life expectancy are now mainly due to declining mortality among those who are older (Christensen et al. 2009)[1]. Statistics are unclear, however, if the added years in older age are being experienced in good health or whether the added years of older age are lived mainly in poor health (Crimmins and Beltran-Sanchez, 2011).

The WHO estimates that between 2015 and 2050, the proportion of the world’s population over 60 years will nearly double from 12 to 22% [2] and the proportion of those aged 80 years and older will almost quadruple. Most health problems of older age result from gradually developing chronic diseases, which become more common with age. The four main types are cardiovascular diseases, cancers, diabetes and chronic respiratory diseases such as chronic obstructive pulmonary disease. Other common conditions in older age include hearing loss, cataracts and refractive errors, back and neck pain and osteoarthritis, depression and dementia. As people age, they are more likely to experience several of these conditions simultaneously.

Many can be prevented or delayed by engaging in healthy behaviours (Haveman-Nies et al., 2002; Michel et al., 2008; Paterson et al., 2010; Hrobonova et al., 2011; Estruch et al, 2013; Tak et al., 2013; Arem et al., 2015; Richard et al., 2017; Xi et al., 2017; Li et al., 2018). A healthy lifestyle, therefore, contributes to a longer healthier life and healthier ageing. Various studies including various meta-analyses have shown that the more healthier lifestyle factors older individuals have, the longer they will live (Larsson et al., 2017; Colpani et al., 2018; Jayedi et al., 2020; Knoops et al., 2004; Keyes et al., 2019, van den Brandt and Brandts, 2020, Zhang et al., 2020). Healthy lifestyle factors studied in these cases included not smoking, a nutritious diet, a healthy body weight, being physically active, and consuming alcohol in moderation.

Widespread health inequities exist, however, both between and within population groups, such that lower socioeconomic groups experience higher levels of alcohol-related harm than wealthier groups with the same level of alcohol consumption (Wilkinson and Marmot, 2003). For example, disadvantaged individuals are typically at least twice as likely to experience serious illness or premature death compared to more advantaged individuals (Wilkinson and Marmot, 2003). In addition, concurrent experience of several forms of socioeconomic disadvantage is known to exacerbate inequities in alcohol-related mortality and morbidity (Rahav et al., 2006; Graham, 2007; CSDH, 2008).

The study by Ortolá et al. (2024) is interesting because it concerns an increasingly larger population group with complex health conditions and an increasing burden on our healthcare system. Insight into healthy habits may help to advise people on their lifestyle and help to prevent adverse health outcomes. It is, however, surprising that they do not find any protection from light or moderate alcohol consumption on their main outcomes ­— total, cardiovascular disease and cancer mortality — whereas other studies have shown such beneficial effects. This includes the study by Jani et al. (2021), also based on a large prospective cohort study of UK Biobank (UKB)[3] participants of more than 300,000 subjects where outcomes were ascertained over a 9-year median follow-up period.

Critique

Bias may have contributed to the data presented and the conclusions drawn by the authors. Their definition of alcohol consumption patterns already introduces bias. Alcohol consumption is assessed by self-reporting the frequency and mean amount of the main types of alcoholic beverages consumed. Based on these self-reports total alcohol consumption was calculated, and their alcohol consumption pattern was classified. The classification was ´occasional´, ´moderate risk´ and ´high risk´. This means that the authors beforehand assumed that alcohol consumption in the moderate and high ranges would have a detrimental effect on their health.

Also, an average alcohol consumption calculated as grams per day is not to be considered as an alcohol consumption pattern. In an alcohol consumption pattern, both alcohol consumption frequency and the amount of alcohol consumed per occasion is important.  Alcohol consumed in moderation has been shown to be beneficial for overall mortality and cardiovascular mortality, with drinking frequency as an additional beneficial factor, in that the more frequently alcohol is consumed in moderation, the stronger the negative association with cardiovascular mortality (Mukamal et al., 2003).

Consequently, Rehm et al. (2001) emphasised the “importance of routinely including measures of drinking patterns into future epidemiologic studies on alcohol-related mortality”. They found that when the largest categories of equivalent average consumption volume were divided into people with and without heavy drinking occasions, serving as an indicator of drinking patterns, this differentiation proved important in predicting mortality. Light to moderate drinkers had higher mortality risks when they reported heavy drinking occasions (defined by either eight drinks per occasion or getting drunk at least monthly). Similarly, when the category of ex-drinkers was divided into people who did or did not report heavy drinking occasions in the past, people with heavy drinking occasions had a higher mortality risk.

Further, drinking amounts and patterns vary widely for drinkers depending on numerous factors which include with/without food, food frequency, quantity frequency, on and off-premise pour sizes, and ethanol concentration of various alcoholic beverages (Greenfield and Kerr, 2009) – all of which significantly influence blood alcohol concentration and hence the size and type of effect on the body’s organs, tissues and cells (Pikaar et al., 1988;  Quertemont and Didone, 2006; Stockley and Saunders, 211). Greenfield and Kerr (2009) highlight the importance of diaries in accurately assessing consumption to reduce potential bias and confounding.

Interestingly, or better disappointedly, there is no control group of older adults who do not drink alcohol. For a fair and just interpretation of the effects of alcohol, a control group of non-drinkers or never-drinkers is essential. Ortolá et al. (2024) did not include non-drinkers in their analysis and presented it as a methodological improvement. However, both groups were present in the cohort and identified as such. The methods section on statistical analysis even indicates that 10,456 never-drinkers and 8,295 former drinkers were excluded from the analysis. It would have been methodologically correct to include both the former drinkers and the never-drinkers in their analysis to show their proposition.

The authors state that occasional drinkers would prevent selection bias caused by misclassification of former drinkers and palliate residual confounding because they (occasional drinkers) are more like light drinkers than are never drinkers. The latter suggests that never-drinkers are very different persons who are not comparable to those who drink, even those who drink lightly or occasionally. It is hard to imagine what those important differences would be and how these differences would have affected the outcomes of this study and all other studies from the same cohort. It would have been informative and insightful to additionally report on the analyses including a methodologically correct control group. It would have made the conclusions, when similar, stronger.

The authors also excluded 20,167 known binge drinkers, who are those who consumed > 6 units of alcohol in one session. This aspect of alcohol consumption has been evaluated once at the beginning of the study without follow-up as all other aspects of alcohol consumption. Authors were, therefore, unable to assess whether this group consists of consistent binge drinkers or also comprises persons who occasionally binge or had one binge in their lifetime. Having 5 units on Friday night and Saturday night may still translate into classification as a low-risk drinker (10 x 8 g/7 = 11.4 g/d) in Ortola et al. (2024)’s methodology. So, the exclusion of one-time bingers and including weekend heavy drinkers as low-risk drinkers still contributes to the misclassification of drinkers, which may have serious consequences for the interpretation of the data. Of the total UK Biobank population of 217,462 participants 60 years and older, 82,359 participants, which is 38%, were excluded due to their incomplete or undesired alcohol consumption report.

Cox regression models were used and corrected for baseline sociodemographic, lifestyle and clinical characteristics. Lifestyle factors include smoking, physical activity, and TV watching time. It seems that additional important lifestyle factors such as diet and body weight were not included in the models, which is a major omission. This omission may have affected the outcomes.

Preference for wine is motivated by the following sentence: “However, some studies have observed

benefits of alcohol on unhealthy aging or frailty, especially of light alcohol intake (18,19) and of a

Mediterranean alcohol drinking pattern, defined as moderate alcohol consumption, preferably wine

and accompanying meals, (14,20) suggesting that the protective associations of these potentially

beneficial drinking patterns might be greater in individuals with ill health, although they might be due

to the aforementioned methodological issues. (5)”

Apart from the fact that it is difficult to understand what the authors want to say, the use of references #18 and #19 is incorrect. Reference #18 (Daskalopoulou et al., 2018) is a meta-analysis looking at the associations between smoking and alcohol consumption and healthy aging. They find that drinkers compared with non-drinkers (1.28, 95% CI 1.08 to 1.52), light drinkers compared with non-drinkers (1.12, 95% CI 1.03 to 1.22), moderate drinkers compared with non-drinkers (1.35, 95% CI 0.93 to 1.97) and high drinkers compared with non-drinkers (1.25, 95% CI 1.09 to 1.44) were all positively associated with healthy aging. Also reference #19 (Kojima et al., 2018) is not just a study but a meta-analysis of all studies on this topic showing that the highest alcohol consumption was associated with a lower frailty index with a pooled OR of 0.44, 95%CI = 0.19–1.00, P = 0.05.

Correct referencing should be an important service to the reader, not a misleading representation of the state-of-the-art literature.

Specific Comments from Forum Members

Forum member Ellison suggests that “given the exclusion of lifetime non-drinkers as an appropriate control group, and many other exclusions such as binge drinkers, it is not possible to judge whether (or not) alcohol consumption had the effects attributed by the authors.  The classification of the level of drinking is based primarily on the number of drinks per week, so it is difficult to know whether each category consisted primarily of regular low-dose drinkers or non-drinkers all week who had heavy drinking on the weekends.

The adjustments, as confounders, for many other risk factors and diseases in their analyses may well have influenced the results if they included conditions such as diabetes or cardiovascular risk factors that have been shown to be favourably affected by alcohol.  As stated so well by other reviewers, having limited information on the pattern of drinking weakens their analyses, as the combination of type of beverage, with or without food, on a regular basis versus only on a few days a week, etc., must be considered together to define the pattern of drinking most associated with healthy outcomes.

Essentially all well-done cohort studies that have controlled for multiple risk factors, including key socio-economic factors, have shown a significant reduction in total and cardiovascular mortality among light and moderate drinkers.  The fact that the current analysis gave different results suggests that these analytic problems may have influenced their reported outcomes.”

Forum member Skovenborg considers “two biases mentioned by Ortola et al. (2024) which are outlined in their reference #5,

Healthy survivor bias: “alcohol is a leading contributing cause of deaths from unintentional injuries and violence among young and middle-aged adults.” 

Accordingly, what Naimi et al. (2017) and Stockwell et al. (2016, 2024) want us to believe is that the aged population of drinkers, that have survived their drinking youth without dying from violence or injuries, are ‘healthy survivors’ favoured by a ‘healthy survivor’ protection against cardiovascular mortality.

Misclassification or exclusion of former drinkers: “including former drinkers with life-time abstainers ‘contaminates’ the non-drinking reference group with less healthy individuals, including some whose poor health is attributable to alcohol. To mitigate this bias, it is now recognized that the reference group of non-drinkers should be comprised only of those who have never or only rarely consume alcohol.”

To clarify what ‘rarely consume alcohol’ means, the following quote is from Stockwell et al. (2016): “Following Fillmore et al. (2006), lifetime abstention was strictly defined as zero consumption and did not include studies with any level of occasional lifetime or past-year drinking (e.g., less than 12 drinks or “rarely” or “hardly ever” drinking). Such self-reported infrequent drinkers have been shown to greatly underreport their consumption.”

Accordingly, Ortola et al. (2024)’s use of ‘occasional drinkers’ as a reference group is not what they call ‘an important methodological improvement’ but a serious flaw according to Stockwell et al. (2016) that would disqualify the results of their study. Furthermore, the group of occasional drinkers may drink <2.86 g alcohol/day = <20 g alcohol/week which actually place a number of these occasional drinkers in the light drinker’s category according to the definition of light drinking used in a number of cohort studies: >1 to <6 drinks/week.”

Furthermore, reference #6 (GBD study of 2016) is quoted as support for the statement “no drinking at all or less is better”. The authors had access to the updated GBD study of 2020 that found that small amounts of alcohol may be beneficial for some older adults, and the daily threshold at which health risks increase is between 1.5 to 3.0 standard drinks for drinkers aged 60 years and older which is the age of the UK Biobank Cohort studied by Ortola et al. (2024).

Finally, a recent combined analysis of alcohol consumption and dementia risk (Mewton et al. 2023), another common health problem of older age, clearly showed that “when compared with abstainers, the risk for dementia was lower in occasional [hazard ratio (HR) = 0.78; 95% confidence interval (CI) = 0.68–0.89], light–moderate (HR = 0.78; 95% CI = 0.70–0.87) and moderate–heavy drinkers (HR = 0.62; 95% CI = 0.51–0.77). There was no evidence of differences between life-time abstainers and former drinkers in terms of dementia risk (HR = 0.98; 95% CI = 0.81–1.18).” Indeed, abstinence from alcohol appears to be associated with an increased risk for all-cause dementia.”

In addition, Forum member Waterhouse states that he is “particularly surprised that there was no cohort of non-drinkers in the study.  Were the authors trying to hide the risks of not drinking?” 

Following on, Forum member Harding has two comments.  “First, the anti-alcohol bias among the authors is apparent from their classification of alcohol consumption, all of which is regarded as ‘risky’. Second, the absence of an abstainer category (even though there were clearly abstainers in the cohort) means that the usual J-shaped curve seen in numerous similar studies is not apparent, and so mortality risk starts increasing from the lowest level of consumption.  Epidemiological data of this nature has been presented like this before, e.g. Wood et al. (2018), although in that case the abstainer data was tucked away in the Appendix.  When data is presented like this, it is not surprising that moderate alcohol consumers have a higher cancer risk, because they are benefiting from the cardio-protective effect of moderate consumption and are therefore living long enough to die of cancer and other conditions.”

Forum member de Gaetano similarly drew our attention to a commentary on Wood et al. (2018) by Astrup et al. (2018), which was also mentioned by Forum member Harding. “Essentially, removing the abstainers as controls lets the J-shaped curve disappear, while it reappears when abstainers are re-introduced (in the original paper, these groups were only included in the Appendix).”

Invited Forum member Fradera comments that “the way I understand it was the purpose of this study (as quoted by the authors) is:

•   to investigate the associations of several potentially beneficial alcohol consumption patterns, such as, consumption of low amounts of alcohol, wine preference, and drinking only during meals, with all-cause, cancer, and CVD mortality in older adults; and

•   to examine whether the relationship is modified by health-related or socioeconomic risk factors.

 However, in their results/conclusions, Ortola et al. (2024) state that “In this cohort study of older drinkers from the UK, even low-risk drinking (compared to occasional drinking) was associated with higher mortality among older adults with health-related or socioeconomic risk factors”. They appear fearful of mentioning the potential positive effects of drinking wine with meals. If you look at all the tables, wine drinkers do not have an increased risk of cancer, CVD and all-cause mortality. Even with health-related and socioeconomic risk factors, there is no increased risk if wine is consumed with the meals (Table 3 and eTable2).

For me, the conclusions based on their purpose would be: The current study found a reduced risk of both cancer and all-cause mortality among individuals who consume wine with meals, compared to those who may drink outside of a meal. And then you can explain that in those with at least one health-related or socioeconomic risk factor, low to moderate drinking might be risky. So, the increased risk for low and moderate drinkers of any alcoholic beverage appears to be restricted only to individuals with at least one existing health-related or socioeconomic risk factor.

The message then would be that this study confirmed that the Mediterranean drinking pattern – moderate wine consumption with meals – was associated with a reduced risk of cancer and all-cause mortality compared to those who drank outside meals. Moderate wine consumption with meals was not related to an increased cancer and all-cause mortality risk among older UK adults.

Study limitations include:

• the UK Biobank cohort is more affluent, white, and mostly wine drinkers primarily living in England. The results of studies based on this population, may not apply to other populations globally. I assume that the participants were considered to have socioeconomic risk factors if they lived in more deprived areas (TDI > 0) and not, if they lived in more affluent areas (TDI < 0); 
• non-drinkers were not included in the reference group;
• based on this single study, the contrasting results of the vast number of previous studies that examined the association between wine/alcoholic beverages and mortality risks cannot be disregarded;
• data about alcohol use was self-reported “How often do you drink alcohol?” If individuals responded positively and drank more than once or twice a week, they were asked: “In an average WEEK, how many glasses of RED wine would you drink?”; and
• nothing is known about eating habits, only lifestyle.

Forum member Parente similarly highlights the statistics contained in Tables 3 and eTable 2 that “clearly show a reduced risk of both cancer and all-cause mortality among individuals who consume wine with meals, compared to those who may drink outside of a meal. And then you can explain that in those with at least one health-related or socioeconomic risk factor, low to moderate drinking might be risky”.

Concluding comments

The Forum concludes that numerous limitations like not using an appropriate control group and using limited information on drinking quantity, drinking pattern and eating habits, may well explain why this single study contrasts the vast number of previous studies showing that light to moderate alcohol consumption is associated with a reduced mortality in older adults.

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Comments on this critique by the International Scientific Forum on Alcohol Research were provided by the following members:

Henk Hendriks, PhD, Netherlands

Creina Stockley, PhD, MBA, Independent consultant and Adjunct Senior Lecturer in the School of Agriculture, Food and Wine at the University of Adelaide, Australia

R. Curtis Ellison, MD, Section of Preventive Medicine/Epidemiology, Boston University School of Medicine, Boston, MA, USA

Erik Skovenberg, MD, specialized in family medicine, member of the Scandinavian Medical Alcohol Board, Aarhus, Denmark

Andrew Waterhouse, PhD, Department of Viticulture and Enology, University of California, Davis, USA

Richard Harding, PhD, Formerly Head of Consumer Choice, Food Standards and Special Projects Division, Food Standards Agency, UK

Giovanni de Gaetano, MD, PhD, Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo NEUROMED, Pozzilli, Italy

Arne Svilaas, MD, PhD, General practice and lipidology, Oslo University Hospital, Oslo, Norway

Ursula Fradera, RDN, MSC, Project Manager, Deutsche Weinakademie GmbH, Germany

Fulvio Ursini, MD, Dept. of Biological Chemistry, University of Padova, Padova, Italy

Mladen Boban, MD, PhD, Professor and Head of the Department of Pharmacology, University of Split School of Medicine, Croatia

Fulvio Mattivi, MSc, Scientific Advisor, Research and Innovation Centre, Fondazione Edmund Mach, in San Michele all’Adige, Italy

Monika Christmann, PhD, Head of Institute, Department of Enology and Professorship for Enology, Hochschule Geisenheim University, Germany

Pierre-Louis Teissedre, PhD, Faculty of Oenology–ISVV, University Victor Segalen Bordeaux 2, Bordeaux, France

Matilda Parente, MD, consultant in molecular pathology/genetics and emerging technologies, San Diego, CA, USA

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