Alcohol Intake and Risk of Ischemic and Haemorrhagic Stroke: Results from a Mendelian Randomisation Study

다국어 초록 (Multilingual Abstract)

Background and Purpose To test whether alcohol intake, both observational and estimated by genetic instruments, is associated with risk of ischemic and haemorrhagic stroke.
Methods We used data from the Copenhagen City Heart Study 1991 to 1994 and 2001 to 2003, and the Copenhagen General Population Study 2003 to 2012 (n=78,546). As measure of alcohol exposure, self-reported consumption and genetic variation in alcohol metabolizing genes (alcohol dehydrogenase ADH1B and ADH1C) as instrumental variables were used. Stroke diagnoses were obtained from a validated hospital register.
Results During follow-up 2,535 cases of ischemic and haemorrhagic stroke occurred. Low and moderate alcohol intake (1 to 20 drinks/week) was associated with reduced risk of stroke. The hazard ratios associated with drinking 1 to 6, 7 to 13, and 14 to 20 drinks/week were 0.84 (95% confidence interval [CI], 0.76 to 0.92), 0.83 (95% CI, 0.73 to 0.94), and 0.84 (95% CI, 0.73 to 0.97), respectively, compared with drinking <1 drink/day. ADH1B and ADH1C genotypes were not associated with risk of stroke. Further analysis to test the included measures revealed that increasing alcohol intake (per 1 drink/day) was positively associated with risk of alcoholic liver cirrhosis, but not associated with risk of stroke, and that increasing blood pressure (per systolic 10 mm Hg) was not associated with risk of alcoholic liver cirrhosis, but positively associated with risk of stroke.
Conclusions Low and moderate self-reported alcohol intake was associated with reduced risk of stroke. The result was not supported by the result from the causal genetic analysis.

참고문헌 (Reference)

1 Nordestgaard BG, "The effect of elevated body mass index on ischemic heart disease risk: causal estimates from a Mendelian randomisation approach" 9 : e1001212-, 2012

2 Juel K, "The Danish registers of causes of death" 46 : 354-357, 1999

3 Helweg-Larsen K, "The Danish register of causes of death" 39 (39): 26-29, 2011

4 Pedersen CB, "The Danish civil registration system" 39 (39): 22-25, 2011

5 Andersen TF, "The Danish National Hospital Register. A valuable source of data for modern health sciences" 46 : 263-268, 1999

6 Schnohr P, "The Copenhagen City Heart Study: osterbroundersogelsen. Tables with data from the third examination 1991-94" 3 (3): H1-H83, 2001

7 Lu M, "Stroke incidence in women under 60 years of age related to alcohol intake and smoking habit" 25 : 517-525, 2008

8 Truelsen T, "Stroke case fatality in Denmark from 1977 to 1992: the Copenhagen City Heart Study" 21 : 22-27, 2002

9 Choi NG, "Sociodemographic characteristics and health status of lifetime abstainers, exdrinkers, bingers, and nonbingers among baby boomers and older adults" 51 : 637-648, 2016

10 Ng Fat L, "Persistent longstanding illness and non-drinking over time, implications for the use of lifetime abstainers as a control group" 68 : 71-77, 2014

11 Sethi AA, "Nanogen microelectronic chip for large-scale genotyping" 50 : 443-446, 2004

12 Lawlor DA, "Mendelian randomization: using genes as instruments for making causal inferences in epidemiology" 27 : 1133-1163, 2008

13 Smith GD, "Mendelian randomization: prospects, potentials, and limitations" 33 : 30-42, 2004

14 Jorgensen AB, "Loss-of-function mutations in APOC3 and risk of ischemic vascular disease" 371 : 32-41, 2014

15 Schumann G, "KLB is associated with alcohol drinking, and its gene product beta-Klotho is necessary for FGF21 regulation of alcohol preference" 113 : 14372-14377, 2016

16 Nielsen NR, "Is the effect of alcohol on risk of stroke confined to highly stressed persons?" 25 : 105-113, 2005

17 Palmer TM, "Instrumental variable estimation of causal risk ratios and causal odds ratios in Mendelian randomization analyses" 173 : 1392-1403, 2011

18 Thomsen M, "Inflammatory biomarkers and exacerbations in chronic obstructive pulmonary disease" 309 : 2353-2361, 2013

19 Wium-Andersen MK, "Increased alcohol consumption as a cause of alcoholism, without similar evidence for depression: a Mendelian randomization study" 44 : 526-539, 2015

20 Ellervik C, "Hereditary hemochromatosis genotypes and risk of ischemic stroke" 68 : 1025-1031, 2007

21 Bjerregaard P, "Genetic variation in alcohol metabolizing enzymes among Inuit and its relation to drinking patterns" 144 : 239-244, 2014

22 Way M, "Genetic variants in or near ADH1B and ADH1C affect susceptibility to alcohol dependence in a British and Irish population" 20 : 594-604, 2015

23 Lawlor DA, "Exploring causal associations between alcohol and coronary heart disease risk factors: findings from a Mendelian randomization study in the Copenhagen General Population Study" 34 : 2519-2528, 2013

24 Hatano S, "Experience from a multicentre stroke register: a preliminary report" 54 : 541-553, 1976

25 Wium-Andersen MK, "Elevated C-reactive protein, depression, somatic diseases, and allcause mortality: a mendelian randomization study" 76 : 249-257, 2014

26 Larsson SC, "Differing association of alcohol consumption with different stroke types: a systematic review and meta-analysis" 14 : 178-, 2016

27 Munoz X, "Association of alcohol dehydrogenase polymorphisms and life-style factors with excessive alcohol intake within the Spanish population (EPIC-Spain)" 107 : 2117-2127, 2012

28 Tolstrup JS, "Alcoholism and alcohol drinking habits predicted from alcohol dehydrogenase genes" 8 : 220-227, 2008

29 Klatsky AL, "Alcohol use and subsequent cerebrovascular disease hospitalizations" 20 : 741-746, 1989

30 Mukamal KJ, "Alcohol use and risk of ischemic stroke among older adults: the cardiovascular health study" 36 : 1830-1834, 2005

31 Tolstrup JS, "Alcohol intake, alcohol dehydrogenase genotypes, and liver damage and disease in the Danish general population" 104 : 2182-2188, 2009

32 Iso H, "Alcohol intake and the risk of cardiovascular disease in middle-aged Japanese men" 26 : 767-773, 1995

33 Zhang C, "Alcohol intake and risk of stroke: a dose-response meta-analysis of prospective studies" 174 : 669-677, 2014

34 Leppala JM, "Alcohol consumption and stroke incidence in male smokers" 100 : 1209-1214, 1999

35 Djousse L, "Alcohol consumption and risk of ischemic stroke: the Framingham Study" 33 : 907-912, 2002

36 Bos S, "Alcohol consumption and risk of cardiovascular disease among hypertensive women" 17 : 119-126, 2010

37 Mukamal KJ, "Alcohol consumption and risk of atrial fibrillation in men and women: the Copenhagen City Heart Study" 112 : 1736-1742, 2005

38 Bazzano LA, "Alcohol consumption and risk for stroke among Chinese men" 62 : 569-578, 2007

39 Kumari M, "Alcohol consumption and cognitive performance: a Mendelian randomization study" 109 : 1462-1471, 2014

40 Donahue RP, "Alcohol and hemorrhagic stroke. The Honolulu Heart Program" 255 : 2311-2314, 1986

41 Guo R, "Alcohol and acetaldehyde in public health: from marvel to menace" 7 : 1285-1301, 2010

42 Hernan MA, "A structural approach to selection bias" 15 : 615-625, 2004

43 Stampfer MJ, "A prospective study of moderate alcohol consumption and the risk of coronary disease and stroke in women" 319 : 267-273, 1988

44 Brondum-Jacobsen P, "25-Hydroxyvitamin D and symptomatic ischemic stroke: an original study and meta-analysis" 73 : 38-47, 2013

45 Smith GD, "'Mendelian randomization': can genetic epidemiology contribute to understanding environmental determinants of disease?" 32 : 1-22, 2003