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Stroke. 2005;36:1835-1836

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(Stroke. 2005;36:1835.)
© 2005 American Heart Association, Inc.

Original Contributions

Editorial Comment—Alcohol and Stroke

An Epidemiological Labyrinth

Arthur L. Klatsky, MD

Senior Consultant in Cardiology, Kaiser Permanente Medical Care Program, Oakland, California


Key Words: epidemiology

According to the seventh edition of Webster’s New Collegiate Dictionary, the definition of labyrinth is "something extremely tortuous or complex in structure, arrangement, or character." The investigator who studies the relations of alcohol drinking to stroke chooses a tortuous path. Multiple issues need consideration. (1) Stroke is not one disease. There are disparities in risk factors of the major stroke types, hemorrhagic stroke (HS), and ischemic stroke (IS), and of their subdivisions.1–5 (2) Several cardiovascular conditions have independent relations to alcohol drinking and also to ≥1 stroke types; these include systemic hypertension (HTN), dilated cardiomyopathy, atrial arrhythmias, and coronary heart disease.6,7 (3) As always with respect to alcohol, light-moderate and heavy drinking play quite different roles. (4) Cigarette smoking, a strong adverse predictor of HS and IS, is correlated with alcohol drinking and must be carefully controlled. (5) Drinking pattern and beverage choice play a role; binge drinking, in particular, increases risk.1 (6) Drinking habits change. (7) Nonalcohol components of specific beverages might play a role. (8) There are potential interactions of alcohol with antithrombotic treatment, perhaps especially with warfarin anticoagulation. (9) Under-reporting by heavy drinkers could produce a spuriously low threshold for harmful effects or an apparent continuous relation when a true threshold effect exists.

Considering the potentially labyrinthine interactions between these factors, it is hardly surprising that reports about alcohol and "stroke" are conflicting.

Heavy drinking (defined here as >2 standard-sized drinks per day) is related to increased prevalence of HTN,7,8 and alcohol has antithrombotic effects.9,10 Thus, it is easy to understand why heavy drinking is associated with increased HS risk, and there is some consensus about this relation in relevant reports.1–4,11 The antithrombotic actions of alcohol might also result in increased HS risk at moderate drinking levels, but reports differ about whether lighter drinking increases HS risk or is unrelated.1,11,12 The alcohol–HS relation seems similar for subarachnoid and intracerebral hemorrhage.1,11

Reports are less concordant about alcohol–IS relations, but several analyses suggest a U-shaped or J-shaped curve of drinking amount to IS risk.13–16 Data are sparse about alcohol relations to specific IS subsets such as cardioembolic events, aortic arch/great vessel emboli, or intracerebral thrombi. Associations of alcohol with these IS subgroups might vary.5 For example, plausible interactions of heavy drinking with cardiomyopathy, atrial fibrillation, and HTN might increase risk of cardioembolic stroke and account for some of the upturn at heavy intake in the U- or J- shaped alcohol–IS curve. Simultaneously, protection against atherothrombotic disease processes by light-moderate drinking might reduce risk of aortic arch embolism or intracerebral thrombosis.

The insightful analysis of alcohol drinking and IS risk in older persons by Mukamal et al in this issue of Stroke18 confirms a lower IS risk among light drinkers, although the strength of this apparent protection is not robust. The investigators introduce another level of sophistication by demonstrating an interaction of the alcohol–IS relationship with the apolipoprotein E gene epsilon4 (APOE4). Lowered risk of IS among drinkers is limited to APOE4-negative persons. Because this allele has been associated with increased risk of vascular disease, lower high-density lipoprotein (HDL) cholesterol, and blunted alcohol–HDL effect,19 these data offer tantalizing possible perception of a plausible biological mechanism by which light-moderate alcohol drinking might protect against IS.

Laudably, Mukamal et al18attempted to study IS subsets. Yet, despite expert advice and presumed widespread use of modern imaging methods, they were able to assign a specific etiology to <50%. In their older population, half of those who could be classified were considered cardioembolic, a subtype with less hypothetical basis for protection by alcohol. Less protection by alcohol against cardioembolic IS was indirectly suggested by a 2001 Kaiser Permanente cohort report17 that presented data according to presence or absence of atrial fibrillation. In that analysis of 2014 IS subjects, there was a U-shaped relationship between alcohol drinking and risk, with a nadir at usual intake of 1 to 2 drinks per day (relative risk [RR; 95% CI] versus lifelong abstainers=0.8 [0.6 to 0.9]). Among 257 patients in atrial fibrillation at the time of IS, the RR (CI) was 1.1 (0.7 to 1.7) versus 0.7 (0.6 to 0.8) among 1757 persons without atrial fibrillation.17 A substantial preponderance of the atrial fibrillation subjects presumably had a cardioembolic event.

Results may depend on models used. For example, as a possible intermediary in alcohol–stroke relations, HTN should not be controlled except, as was done in the Mukamal et al analysis,18 to see its effect on the data. It is noteworthy that introduction of HTN into the model had little effect on risk estimates,18 presumably because there were few heavy drinkers. Persons with known baseline cardiovascular disease were eliminated from the study population,18 properly so because such history could influence drinking habits. If included among the nondrinking reference group, "sick quitters" might spuriously increase their risk of IS. Yet persons with pre-existent atherothrombotic disease represent a high-risk group that, hypothetically, might benefit most from protective effects of alcohol and might be the best choice for a randomized, controlled trial.

The health professional looking for advice guidelines will not find a simple message suitable for all.20,21 Intrepid epidemiologists will continue to explore the alcohol–stroke labyrinth. Ultimately, answers will be found, but one can reliably predict that the path will be neither easy nor straight.


*    References
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 *References
 

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  2. Camargo CA Jr. Case-control and cohort studies of moderate alcohol consumption and stroke. Clin Chim Acta. 1996; 246: 107–119.[CrossRef][Medline] [Order article via Infotrieve]
  3. Reynolds K, Lewis B, Nolen JD, Kinney GL, Sathya B, He J. Alcohol consumption and risk of stroke: a meta-analysis. J Am Med Assoc. 2003; 289: 579–588.[Abstract/Free Full Text]
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  7. Klatsky AL. Alcohol and cardiovascular health. Integr Comp Biol. 2004; 44: 58–62.
  8. Klatsky AL. Alcohol and hypertension. In: Operil S, Weber M, eds. Hypertension. Philadelphia, Pa: W.B. Saunders Co; 2000: 211–220.
  9. Hendriks FJ, van der Gang MS. Alcohol, anticoagulation and fibrinolysis. In: Chadwick DJ, Goode JA, eds. Alcohol and Cardiovascular Diseases. New York, NY: Wiley; 1998: 111–124.
  10. Booyse FM, Parks DA. Moderate wine and alcohol consumption: beneficial effects on cardiovascular disease. Thromb Haemost. 2001; 86: 517–528.[Medline] [Order article via Infotrieve]
  11. Klatsky AL, Armstrong MA, Sidney S, Friedman GD. Alcohol drinking and risk of hemorrhagic stroke. Neuroepidemiology. 2002; 21: 115–122.[CrossRef][Medline] [Order article via Infotrieve]
  12. Thrift AG, Donnan GA, McNeil JJ. Heavy drinking, but not moderate or intermediate drinking, increases the risk of intracerebral hemorrhage. Epidemiology. 1999; 10: 307–312.[CrossRef][Medline] [Order article via Infotrieve]
  13. Sacco RL, Elkind M, Boden-Albala B, Lin IF, Kargman DE, Hauser WA, Shea S, Paik MC. The protective effect of moderate alcohol consumption on ischemic stroke. J Am Med Assoc. 1999; 281: 53–60.[Abstract/Free Full Text]
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  18. Mukamal KJ, Chung H, Jenny NS, Kuller LH, Longstreth WT, Jr Mittleman M, Burke MS, Cushman M, Beauchamp NJ, Siscivick DS Alcohol use and risk of ischemic stroke among older adults: the Cardiovascular Health Study. Stroke. 2005; 36: 1830–1834.[Abstract/Free Full Text]
  19. Djousse L, Pankow JS, Arnett DK, Eckfeldt JH, Myers RH, Ellison RC. Apolipoprotein E polymorphism modifies the alcohol-HDL association observed in the National Heart, Lung, and Blood Institute Family Heart Study. Am J Clin Nutr. 2004; 80: 1639–1644.[Abstract/Free Full Text]
  20. Gorelick PB, Sacco RL, Smith DB, Alberts M, Mustone-Alexander L, Rader D, Ross JL, Raps E, Ozer MN, Brass LM, Malone ME, Goldberg S, Booss J, Hanley DF, Toole JF, Greengold NL, Rhew DC. Prevention of a first stroke: a review of guidelines and a multidisciplinary consensus statement from the National Stroke Association. J Am Med Assoc. 1999; 281: 1112–1120.[Abstract/Free Full Text]
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Related Article:

Alcohol Use and Risk of Ischemic Stroke Among Older Adults: The Cardiovascular Health Study
Kenneth J. Mukamal, Hyoju Chung, Nancy S. Jenny, Lewis H. Kuller, W.T. Longstreth, Jr, Murray A. Mittleman, Gregory L. Burke, Mary Cushman, Norman J. Beauchamp, Jr, and David S. Siscovick
Stroke 2005 36: 1830-1834. [Abstract] [Full Text] [PDF]



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