Alcohol and Chronic Disease: Research into practical application

1. Presented at Alcohol: No Ordinary Commodity Forum 6 Thursday, March 5th, 2009, Toronto Alcohol and Chronic Disease: Research into practical application Jürgen Rehm & Norman Giesbrecht

2. Background of this work WHO and Global Burden of Disease Study Canadian Studies applying the methodology

3. Currently used model for alcohol CRA 2005 (also valid for chronic disease) Population group (individual) Societal Factors Gender Drinking culture Age Alcohol Policy Poverty Marginalization Drinking environment Health care system

4. Cancers Alcohol was found a carcinogen for the following cancers: mouth & oropharyngeal cancer, esophageal cancer, liver cancer, female breast cancer, colorectal cancer

5. Cancers related to average volume and kind of relative risk Typical risk curves for cancer(Corrao et al., 2004) • Alcohol attributable cancers: • Lip & oropharyngeal cancer, esophageal cancer, liver cancer, laryngeal cancer, colorectal cancer female breast cancer • Quantification for continuous risk relationships to be mainly taken from Corrao meta-analyses • Clear dose-response relationship without any protective effect • Clear evidence of effects as low as one drink (breast cancer!)

6. Who determines that alcohol is causal for cancers? • International Agency for Research on Cancer (part of WHO, UN system) • Systematic evaluation 2007 • 26 scientists from 15 countries: • Biology and mechanisms • Epidemiology • Final evaluation based on predetermined criteria (www.iarc.fr)

7. Biological mechanisms of esophageal cancer ALDH2*2 elevatedacetaldehyde Chromosome aberrations Alcohol drinking DNA Adducts Cancer Significant positive association with increased cancer risk Significant pos. association with ALDH2*1/2 genotype Significantly more frequently in alcoholics Alcohol consumptioncauses cancer

8. Consequences for Canada: alcohol-attributable chronic-disease mortality in people aged 69 years or younger in Canada, 2002

9. Conclusions for cancer • The less alcohol, the better, and no alcohol at all clearly would be best for cancer

10. Mental disorders Alcohol dependence and alcohol abuse define the so-called alcohol used disorders (AUD). They are by definition 100% attributable to alcohol. Almost all mental disorders are linked to alcohol. However, causality is not clear, and has only be established for depression. It is a complicated relationship, as alcohol can cause depression, depression can cause AUD, and both are influence by genetic vulnerability.

11. Consequences for Canada: alcohol-attributable chronic-disease mortality in people aged 69 years or younger in Canada, 2002 Mental disorders are often disabling but not fatal

12. Conclusions for mental disorders • Alcohol consumption has some positive psychosocial effects (that is why the majority of us drink), but also constitutes a risk for alcohol use disorders, i.e., alcohol dependence and alcohol abuse. • It has also been shown to be causal for depression

13. Gastrointestinal diseases Alcohol-attributable GI diseases include: esophageal varices, gastro-esophageal hemorrhage, liver cirrhosis, cholelithiasis (protective effect), acute pancreatitis, chronic pancreatitits

14. Relative risk of liver cirrhosis associated with alcohol consumption derived from the random effects fractional polynomial models Women Men Clearly the risk of alcohol consumption is higher for mortality than for morbidity!

15. Main associations • Alcohol causally impacts GI diseases. • The risks are often curvilinear: there is some risk elevation for light to moderate drinking, but the risks increase exponentially and are clearly pronounced for heavy drinking. • The protective effect on cholelithiasis is public health irrelevant.

16. Consequences for Canada: alcohol-attributable chronic-disease mortality in people aged 69 years or younger in Canada, 2002

17. Conclusions for gastrointestinal diseases • Most of the harm from alcohol comes from heavy drinking in this category, but there are no benefits of alcohol consumption of any kind of drinking (with the exception of cholelithiasis, which is not a very public health relevant category).

18. Cardiovascular disease Alcohol causally impacts hypertensive diseases, coronary heart disease, stroke (both ischemic stroke and hemorrhagic stroke)

19. The example of patterns of drinking and CHD • CHD one of the most prevalent causes of disease in established market and emerging economies • Relation to alcohol has been controversially discussed for centuries • Protective effect for some drinking patterns

20. Biological evidence: beneficial effect of moderate regular drinking without any binges(Puddey, et al., 1999; Rehm et al., 2003) • favorable lipid profiles (HDL ) • favorable coagulation profiles (platelet aggregation & fibrinolysis) Both factors explain 50% and more of beneficial effect (Meta-analysis: Rimm et al., 1999) • affects insulin resistence • promotes vasodilation • affects inflammation

21. Biological evidence: detrimental effect of irregular binge drinking (McKee & Britton, 1999; Puddey et al., 1999; Rehm et al., 2003) • increased clotting • reducing threshold for ventricular fibrillation • increase of blood pressure • disadvantageous blood lipid profile (LDL )

22. Biological evidence:drinking with meals (Rehm et al., 2003) • reduced blood pressure • positively affect fibrinolysis • positively affect lipids • reduced absorption of alcohol • increase alcohol elimination rate

23. Conclusion on patterns and CHD • Alcohol can have detrimental and beneficial effects depending on the pattern and volume of drinking • Important considerations: • Volume • Heavy drinking occasions • Regularity • With or outside of meals • The overall relation in one country depends on the mix of drinking patterns

24. Average volume alcohol and CHD in high quality large cohorts

25. Typical picture in large cohort • Corrao et al. (2000) present the typical picture of large well-conducted cohorts • But what is a well conducted cohort? • High completion rate at baseline • Low loss to follow-up • Good measures of outcome (validated endpoints) • But not good alcohol measures on patterns nor representative of drinkers in society (often US doctors, nurses, health professionals, friends of the Cancer society, middle class drinking) => Not enough research on high-risk drinking patterns

26. What happens if we examine people with “bad” (= often normal) drinking patterns? • As expected the beneficial effect disappears! • Examples for looking at people within cohorts with more irregular heavy drinking: • McElduff & Dobson, 1997: case-control study • Murray et al., 2002: cohort study • Trevisan et al., 2001: cohort study • Example for looking at populations with suspected irregular heavy drinking: Sempos et al., 2003 on representative sample of African Americans who showed over NO protective effect; no effect in Brazilian cross-sectional sample

27. Irregular heavy drinking occasions and ischaemic heart disease (IHD) Exposure • Risk group: Irregular heavy drinking occasions measured as intoxication or typical dose ≥60 grams pure alcohol (about 5+ standard drinks) at least monthly • Comparison group: regular drinkers up to 60 grams/day without any or less than monthly heavy drinking occasions • Excluded were occasional drinkers (≤12 drinking occasions per year) and regular heavy drinkers (>60 grams/day)

28. Forest plot of the effect of irregular heavy drinking occasions vs. regular moderate drinking on IHD risk

29. Conclusion on patterns and CHD • CHD is very important cause of disease and thus important in determining health policy (and influencing health policy makers) • Alcohol to CHD relation is complex • Need to know exactly what proportion of population drinks how to predict outcome as light to moderate drinking with binge drinking occasions confers no benefit • Better and standardized pattern measures are necessary! • But conclusions can tentatively be drawn today: alcohol in many parts of the world is consumed in a way that it is detrimental to CHD; Canada may be one of the exceptions according to surveys but severe underreporting!!

30. Consequences for Canada: alcohol-attributable chronic-disease mortality in people aged 69 years or younger in Canada, 2002

31. Conclusions for CVD Overall, only regular and light to moderate patterns, without any occasional heavy drinking, confers a cardioprotective effect. Should be balanced against the risks! Individual decision to drink lightly or to abstain should depend on risk profile of individual!

32. Diabetes There is some evidence that moderate drinking is associated with decreased risk of diabetes.

33. Alcohol & incident type 2 diabetes Figure: Pooled and fitted relative risk estimates and 95% CI band. A) The highest single alcohol consumption measure for women was 52.35 g/day, thus the x-axis is scaled to 60 g/day B) Among men, the single highest alcohol consumption measure was 80.04 g/day

34. Consequences for Canada: alcohol-attributable chronic-disease mortality in people aged 69 years or younger in Canada, 2002

35. Conclusions for diabetes • Overall, again there are indications that effect disappears if there are occasional heavy drinking occasions even with an overall light to moderate drinking style. • Should be balanced against the risks! • Individual decision to drink lightly or to abstain should depend on risk profile of individual!

36. Fetal alcohol syndrome (FAS) Epidemiological work not finished yet.

37. Fetal Alcohol Spectrum Disorder (FASD) FASD is an umbrella term describing the range of effects that can occur in an individual whose mother drank alcohol during pregnancy. These effects may include physical, mental, behavioural and learning disabilities. These consequences are lifelong, and the behavioral and learning difficulties are often greater than the degree of neurocognitive impairment. Fetal alcohol syndrome (FAS) is the most clinically recognizable form of FASD.

38. Fetal Alcohol Syndrome (FAS) FAS is a disorder that occurs in the fetus exposed to alcohol due to mother’s drinking during pregnancy and is characterized by a triad of signs: I. Prenatal and or postnatal growth retardation • Low birth weight and gestational age • Decelerating weight over time not due to nutrition • Disproportional low weight-to-height ratio II. Characteristic facial anomalies (next slide) III. Central nervous system (CNS) neurodevelopmental abnormalities, as in at least one of the following: • Decreased cranial size at birth • Structural brain abnormalities (e.g., microcephaly, partial or complete agenesis of the corpus callosum, cerebellar hypoplasia) • Neurologic hard or soft signs (as age appropriate), such as impaired fine motor skills, neurosensory hearing loss, poor tandem gait, poor eye-hand coordination) (Canadian Pediatric Society Statement, 2002)

39. Some crude estimates of FAS/FASD (not complete triad of symptoms) of prevalence in Canada GENERAL POPULATION • FAS prevalence: 1 to 2 per 1,000 live births (Roberts & Nanson, 2000) • FASD prevalence: 9 in 1,000 live births (PHAC, 2003). • The incidence of infants prenatally exposed to alcohol to be 0.8 per 100 live births (based on 18, 234 infants born in a total of 18 hospitals (Stade et al., in progress). ABORIGINAL POPULATION • FASD prevalence: 190 per 1,000 live births in an isolated community in British Columbia (Robinson et al., 1987). • FAS and partial FAS prevalence: 55–101 per 1,000 in a community in north-eastern Manitoba (Square, 1997). • FAS and related effects prevalence: 46 per 1,000 native Canadian children in the Yukon and 25 per 1,000 in northern British Columbia (Asante & Nelms-Matzke, 1985). • More than half of aboriginal women in northern Manitoba reported consuming alcohol during one or more of their pregnancies (Williams & Gloster, 1999).

40. Alcohol, No Ordinary Commodity:Research and Public Policy Thomas Babor Linda Hill Raul Caetano Harold Holder Sally Casswell Ross Homel Griffith Edwards Esa Österberg Norman Giesbrecht Jürgen Rehm Kathryn Graham Robin Room Joel Grube Ingeborg Rossow Paul Gruenewald Assisted by: Cees Coos, Maristela Monteiro, Shakar Saxena, Maggie Brady, Therese Reitan, Jacek Moskoliwicz Publisher -- Oxford: Oxford University Press, 2003 Sponsored by: The World Health Organization and the Society for the Study of Addiction

41. Ratings of alcohol policy-relevant strategies & interventions Source: Adapted from T. Babor et al. (2003) Alcohol: No ordinary commodity (Table 16.1), by T. Greenfield, et al.( 2007)

42. Best Practices & Practices with Good Support and Feasibility Alcohol taxes** Minimum legal purchase age Gov’t monopoly of retail sales** Sobriety check points Lowered BAC limits Administrative license suspension Graduated licensing for novice drivers Restrictions on hours & days of sale** Restrictions on outlet density** Enforcement of on-premise regulations** Brief interventions for high risk drinkers**

43. Community-based initiatives – a few examples of practical applications • Licensed premises • Raise public awareness of problems associated with on-premise drinking in licensed establishments • Pressure owners to recognize that they have a responsibility to patron behavior • Density of outlets and retail stores • Lobby for a moratorium on increase in outletsper capita • Safe serving practices • Support retailers and service personnel in efforts to refuse service to under-age or intoxicated patrons service to minors, i sales • Municipal alcohol policies (MAP)Brief interventions for high . • Introduce, renew and encourage evaluation • Brief interventions for high risk drinkers • Implement in clinics, hospitals, university settings, via web • Chronic disease prevention networks and associations • Raise awareness of alcohol as a risk factor for chronic disease