Critique 193: The association of reported alcohol intake with the risk of subarachnoid hemorrhage: A meta-analysis – 1 November 2016

Yao X, Zhang K, Bian J, Chen G. Alcohol consumption and risk of subarachnoid hemorrhage: A meta-analysis of 14 observational studies.  Biomedical Reports 2016;5:428-436.

Authors’ Abstract

The association between alcohol consumption and the risk of subarachnoid hemorrhage (SAH) is inconsistent. Thus, meta‑and a dose‑response analyses are presented with the purpose of assessing their associations.

A systematic literature search was performed using Pubmed and Embase electronic databases for pertinent observational studies. Random‑effects or fixed‑effect models were employed to combine the estimates of the relative risks (RRs) with corre­sponding 95% confidence intervals (CIs).  A dose‑response pattern was conducted for further analysis.  The current meta‑analysis includes 14 observational studies reporting data on 483,553 individuals and 2,556 patients.

The combined RRs of light alcohol consumption (<15 g/day) and moderate alcohol consumption (15‑30 g/day) compared with teetotal individuals were 1.27 (95% CI: 0.95, 1.68) and 1.33 (95% CI: 0.84, 2.09), respectively, which indicated no significant association between light‑to‑moderate alcohol consumption and SAH. An increased risk of SAH was noted in heavy alcohol consumption (>30 g/day) when compared with no alcohol consumption, as demonstrated by a result of 1.78 (95% CI: 1.46, 2.17).  Dose‑response analysis showed evidence of a linear association (P=0.0125) between alcohol consump­tion and SAH.  The risk of SAH increased by 12.1% when alcohol consumption was increased by 10 g/day.

Therefore, heavy alcohol consumption was found to be associated with an increased risk of SAH. Furthermore, the association between SAH and alcohol consumption has clinical relevance with regard to risk factor modification and the primary and secondary prevention of SAH.

Forum Comments

Background: Data from epidemiologic studies are quite consistent for the relation of alcohol consumption with certain types of stroke: for ischemic stroke, there seems to be an inverse association with moderate drinking and a possible increase with heavy drinking (a “j-shaped curve”); for hemorrhagic stroke, there seems to be a direct positive association, although some studies suggest that there may be a threshold level for an increase in risk.  Data are mixed on a possible association between the most uncommon type of stroke, subarachnoid hemorrhage (SAH).  This may be due partly to the fact that SAH may relate to congenital abnormalities of the cerebral arteries, with the event itself being triggered by hypertension or abnormalities of coagulation.  The present meta-analysis seeks to provide additional information on the association of reported alcohol consumption and SAH.

Forum member Stockley summarizes the data on alcohol and hemorrhagic stroke, as follows: “The relationship between moderate alcohol consumption and haemorrhagic stroke is less certain than for ischaemic stroke. Some studies have observed a J-shaped relationship while others observed a linear dose-dependent relationship between the amount of alcohol consumed and the risk of haemorrhagic stroke (Klatsky et al, Ariesen et al, Corrao et al, Feigin et al, Patra et al).  If the relation is J-shaped, the ‘optimal’ amount of alcohol is even lower than that for ischaemic stroke.  For example, while Corrao et al calculated a significantly increased risk for ischaemic stroke at 100 g alcohol/day, for haemorrhagic stroke this was calculated at 50 g/day, where heavy alcohol consumption in the review paper is considered to be lower again at only >30 g/day, with risk increasing with each additional 10 g alcohol consumed.  This difference in risk between stroke types may be associated with an alcohol-induced increase in blood pressure in heavier consumers (Klatsky et al, Iso et al).  Also, these observations may reflect the alcohol-induced reduction in blood clotting which decreases the risk of a blood clotting-related events such as a myocardial infarction and an ischaemic stroke, but increases the risk of bleeding or a haemorrhage in the brain (Renaud & de Lorgeril, 1992).”

Other comments by Forum members on present study: This appears to be a well-done analysis using appropriate methodology for a meta-analysis.  Non-drinkers were used as the referent group, those consuming < 15 g/day of alcohol were classified as “light” drinkers, and those consuming 15-30 g/day were classified as “moderate” drinkers (which is up to 2 ½ or 3 typical drinks/day, perhaps a little too high for women).  An obvious weaknesses of the analysis is that reported alcohol data came from a variety of sources, and were evidently only the average intake over a period of time.  There was no information on the pattern of drinking or on the type of beverage consumed.

When looking at heterogeneity among the studies included, it is noted that except for a few of the cohort studies, the number of cases in each separate study was quite small. It is interesting that the two studies showing marked increases in risk for light and moderate drinking were two studies from the 1980s, those of Donahue et al and Stampfer et al, which had only 32 and 28 cases of SAH, respectively.  Most studies showed much less of an effect for other than heavy drinking than these two studies.  Reviewer Skovenborg noted that most of the studies included in this analysis were from countries with a track record of binge drinking, and did not include predominantly wine-consuming countries.

While the estimated RR was increased for both light and moderate drinkers, the authors interpret their data as showing no association (as the differences were not statistically significant) for these groups.  To members of the Forum, viewing the results overall supports perhaps some adverse effects on risk of even light and moderate drinking, as the estimated risk ratio was above 1.0 for both groups.

Reviewer Goldfinger stated: “This is a nice meta-analysis that I believe is well done. Definitions of mild/moderate/heavy drinking is acceptable.  Considering the well-known effects on platelet aggregation and increased blood pressure, the finding of increased SAH in heavy drinkers is not unexpected.  However, I do know that previous reports from Renaud, Lanzmann, and their associates (Renaud et al, 2004) have shown that there is decreased cardiovascular mortality for all levels of blood pressure among moderate consumers of wine, when compared with abstainers.”  Reviewer Skovenborg noted that there were no studies included in the meta-analysis from Mediterranean countries, where wine is the predominant beverage.

Is there a dose-response relation?  The total SAH outcomes in these analyses favor a dose-response relation between alcohol intake and SAH, although in many of the comparisons (e.g., looking separately for men, for women, for cohort studies), the highest estimated risk is for moderate rather than the heavier drinkers.  The authors used data from seven studies for a formal dose-response analysis and found a significant increase in risk at all levels of drinking; from the figures presented in the paper, the increase in risk appears to be about 10% when relating the risk of those consuming 15 g/day when compared with abstainers.

Overall, this study supports an increase in risk of SAH with alcohol consumption, but it does not permit a good estimation of a threshold level. Also, given the heterogeneity of studies, lack of information on many other risk factors, no information on pattern of drinking or type of beverage, it may not be possible to use these results as the basis of new public health recommendations.   Subjects consuming alcohol heavily should obviously be advised to decrease their intake; it is unsure the extent to which such recommendations would affect the overall risk of SAH.  Forum members agreed with the closing statement of the authors that “any suggestion regarding alcohol consumption must be tailored to the risk of each individual subject.”

Net effects of alcohol consumption on risk of total stroke: These data suggest that alcohol consumption, at least heavy drinking, may relate to an increase in the risk of SAH, which is a relatively rare but serious event.  As stated, a similar increase in risk with alcohol has been shown for intracerebral hemorrhagic stroke.  However, it should be pointed out that the large majority of strokes in the Western world are ischemic stroke, which shows a decrease in risk with moderate drinking similar to that of ischemic coronary disease.  Given the greater risk that a stroke in most of the world will be ischemic rather than hemorrhagic in nature, the overall risk of a person having a stroke (of any type) has been found to be lower for light to moderate drinkers than for abstainers.

References from Forum critique

Ariesen MJ, Claus SP, Rinkel GJ, Algra A. Risk factors for intracerebral hemorrhage in the general population: a systematic review.  Stroke 2003;34:2060-2065.

Corrao G, Bagnardi V, Zambon A, La Vecchia C. A meta-analysis of alcohol consumption and the risk of 15 diseases. Prev Med 2004;38:613-619.

Donahue RP, Abbott RD, Reed DM, Yano K: Alcohol and hemorrhagic stroke. The Honolulu heart program. JAMA 1986;255:2311‑2314.

Feigin VL, Rinkel GJ, Lawes CM, Algra A, Bennett DA, van Gijn J, Anderson CS. Risk factors for subarachnoid hemorrhage: an updated systematic review of epidemiological studies.  Stroke 2005;36:2773-2780.

Iso H, Baba S, Mannami T, Sasaki S, Okada K, Konishi M, Tsugane S, JPHC Study Group. Alcohol consumption and risk of stroke among middle-aged men: the JPHC Study Cohort I. Stroke 2004;35:1124-1129.

Klatsky AL, Armstrong MA, Friedman GD, Sidney S. Alcohol drinking and risk of hemorrhagic stroke. Neuroepidemiology 2002;21:115-122.

Patra J, Taylor B, Irving H, Roerecke M, Baliunas D, Mohapatra S, Rehm J. 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.

Renaud S, de Lorgeril M. Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet 1992:339:1523-1526.

Renaud SC, Guéguen R, Conard P, Lanzmann-Petithory D, Orgogozo J-M, Henry O. Moderate wine drinkers have lower hypertension-related mortality: a prospective cohort study in French men.  Am J Clin Nutr 2004;80:621–625.

Stampfer MJ, Colditz GA, Willett WC, Speizer FE, Hennekens CH: A prospective study of moderate alcohol consumption and the risk of coronary disease and stroke in women. N Engl J Med 1988;319:267‑273.

Forum Summary

Data from epidemiologic studies are quite consistent for the relation of alcohol consumption with the different types of stroke: for ischemic stroke, an inverse association with moderate drinking and a possible increase with heavy drinking (a “j-shaped curve”); for hemorrhagic stroke, a direct positive association, although some studies suggest that there may be a threshold level for an increase in risk. Data are mixed on a possible association between the most uncommon type of stroke, subarachnoid hemorrhage (SAH).  The present paper presents results of a meta-analysis relating reported intake of alcohol with subsequent risk of SAH.   It was based on 14 observational studies reporting data on 483,553 individuals and 2,556 patients.

Forum members agree that this study suggests that alcohol intake, especially heavier drinking, increases the risk of SAH, although there was considerable heterogeneity among studies from different parts of the world, there were no countries from the Mediterranean area included, and there was no accounting for pattern of drinking (binge versus moderate regular) or type of beverage, all of which may affect risk.

The authors concluded that there was no relation between light (<15 g/day) or moderate alcohol consumption (15‑30 g/day) compared with abstaining individuals; this was based on statistically insignificant increases in RR of 1.27 (95% CI: 0.95, 1.68) and 1.33 (95% CI: 0.84, 2.09) for these two groups, respectively. However, Forum members suggest that there could be a slight increase in risk even for these two groups.  For heavier drinkers (> 30 g/day, about 2 ½ to 3 typical drinks per day), the data indicate an increase in risk: RR=1.78 (95% CI: 1.46, 2.17).

It should be noted that the overall risk of total stroke is decreased from moderate drinking, as the most common type of stroke is ischemic, and moderate drinking has consistently been shown to lower such risk; this is especially related to lowering the risk of atherosclerotic or embolic clots. However, while rare, SAH is often a devastating disease, and the risk may be increased from alcohol consumption through its effects on decreasing coagulation.

*                *                      *                      *                      *                      *                *

Comments on this publication have been provided by the following members of the International Scientific Forum on Alcohol Research:

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

R. Curtis Ellison, MD, Professor of Medicine & Public Health, Boston University School of Medicine, Boston, MA, USA

Harvey Finkel, MD, Hematology/Oncology, Boston University Medical Center, Boston, MA, USA

Tedd Goldfinger, DO, FACC, Desert Cardiology of Tucson Heart Center, University of Arizona School of Medicine, Tucson, AZ, USA

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

Creina Stockley, PhD, MSc Clinical Pharmacology, MBA; Health and Regulatory Information Manager, Australian Wine Research Institute, Glen Osmond, South Australia, Australia

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

David Van Velden, MD, Dept. of Pathology, Stellenbosch University, Stellenbosch, South Africa

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