Mori TA, Burke V, Beilin LJ, Puddey IB. Randomized Controlled Intervention of the Effects of Alcohol on Blood Pressure in Premenopausal Women. Hypertension 2015;66:00-00. DOI: 10.1161/HYPERTENSIONAHA. 115.05773
Alcohol has been consistently demonstrated to elevate blood pressure (BP) in intervention studies in men. There are uncertainties, however, as to the nature of the relationship in women. We, therefore, determined in healthy premenopausal women the dose-dependent effects of alcohol on ambulatory BP. Twenty-four participants aged 25 to 49 years, with a mean alcohol intake of 202±94 g alcohol/wk and mean 24-hour systolic and diastolic BP of 110.2±8.9/68.9±5.7 mmHg, were randomized to a 3-period cross-over study. Each evening they consumed higher volume red wine (lower level drinkers, 146 g alcohol/wk; higher level drinkers, 218 g alcohol/wk), lower volume red wine (lower level drinkers, 42 g alcohol/wk; higher level drinkers, 73 g alcohol/wk), or dealcoholized red wine, each for a period of 4 weeks.
Higher volume red wine significantly increased 24 hours systolic and diastolic BP relative to dealcoholized red wine (by 2.0±0.6/1.2±0.4 mmHg; P=0.001 and P=0.028, respectively). There were similar changes for higher volume red wine relative to lower volume red wine (by 1.6±0.6/1.4±0.4 mmHg; P=0.014 and P=0.005, respectively). The effects were predominantly on awake rather than asleep BP. There was no significant difference in BP between lower volume red wine and dealcoholized red wine.
We conclude that in healthy premenopausal women regular consumption of alcohol as 200 to 300 mL red wine/d (146–218 g alcohol/wk) elevates 24 hours systolic and diastolic BP. The magnitude of the increase in BP is similar to that previously reported in intervention studies in men.
Overview of trial: While most epidemiologic studies show that alcohol consumption, especially when more than moderate, is associated with an increase in blood pressure, few clinical trials of alcohol and blood pressure have been carried out. The present paper describes the effects among 24 normotensive pre-menopausal women, all of whom were regular drinkers, of the administration of two levels of alcohol in the form of red wine. Subjects were given low amounts of wine and higher amounts of wine during two 4-week intervention periods, with the effects on blood pressure compared with changes when subjects were given similar amounts of dealcoholized red wine.
Prior to the intervention, subjects averaged 202±94 g of alcohol per week, the equivalent of 2 to 3 typical drinks/day. Subjects were divided into a “lower level” group who previously consumed < 200 g/week of alcohol and “higher level” drinkers who previously consumed >200 g/week. Previous “lower level” drinkers were given two levels of alcohol: 100 ml/day of red wine on 4 days per week (the equivalent of 46 g/week of alcohol) and 200 ml/day of red wine (about 146 g/week of alcohol) for another 4-week period. Subjects who were previous “higher level” drinkers were given 100 ml of red wine daily (about 73 g/d of alcohol per week) for 4 weeks and 300 ml/d of red wine (about 218 g/week of alcohol) for another 4 weeks.
The main results are a small but significant increase in 24-hour average blood pressure (+2.0 mmHg systolic and +1.3 mmHg diastolic) with higher levels of red wine but no significant effects (+0.4 mmHg systolic, -0.3 mmHg diastolic) from lower levels of red wine administration, when compared with periods during which dealcoholized red wine was given. The differences in the higher alcohol period were predominantly due to higher awake rather than asleep blood pressures. These findings are similar to results of a limited number of randomized controlled trials of alcohol in men.
Specific comments on the trial by Forum members: Reviewer Van Velden noted: “This study confirms the fact that high levels of alcohol consumption increase BP, as demonstrated in men. Low amounts of alcohol do not seem to have a significant effect, but there are many confounders such as healthy diet, exercise, weight management, etc., that may also play a role. It all boils down to a healthy, responsible lifestyle; alcohol cannot be seen in isolation.”
Reviewer Ellison considered this to be “a well-controlled intervention trial, with confirmation of the reported intake of alcohol of subjects by laboratory measurements.” He also noted: “In their background remarks, the authors discuss effects of alcohol on blood pressure and on ‘hypertension’ together, although these are different outcomes, although obviously related.”
Ellison had some further questions, however, about the levels of alcohol given during the intervention: “The study was done among ‘drinking’ subjects reporting relatively high levels of alcohol intake (the authors report that their average ‘usual’ intake was 202 ±94 g/week of alcohol, or 2 or 3 typical drinks/day). Thus, even with the higher level of alcohol given during the intervention, it was essentially to the same level as the usual level before the trial of many of the subjects. As individual responses are not given in the paper, we cannot be sure how many of the subjects were receiving levels of alcohol that were higher or lower than their usual intake.”
Reviewer Zhang also commented on the fact that there were no previous abstainers included, among whom the effects of alcohol could have been greater than among those in this study. “My major concern is that subjects included in this study were normotensive and regular drinkers. I do not know how long these women had been drinking, but apparently previous alcohol drinking had not increased their blood pressure. In other words these women may be less ‘sensitive’ to alcohol effects on blood pressure. Consequently it could dilute the effect of alcohol on BP. This study differs from another RCT conducted in Israel in which all subjects were non-drinkers before the study and who were then randomly allocated into alcohol or non-alcohol groups (Shai et al, 2007).”
Forum member Waterhouse stated: “Would not it have been a better experimental design to have given all subjects the same ‘high level of alcohol,’ and then compared the response to the high dose versus typical consumption rate to see if habitual consumption would have affected the subject’s response to varying levels of alcohol. Another intervention arm could have been an alcohol drink lacking phenolics, such as vodka.”
Forum member Lanzmann-Petithory commented that the results with other beverages containing alcohol may be different from those seen with red wine in the present study. She referred to previous findings from a study with Serge Renaud showing that moderate wine drinkers had lower risk of death than non-wine drinkers. “In our study, men with systolic blood pressure of 158, 139, or 116 mmHg had significantly lower risks of death from all causes (by 23%, 27%, and 37%, respectively) than did abstainers (Renaud et al).” She also commented on the increases in HDL and decreases in fibrinogen resulting from the red wine administration in this study, which would have decreased the risk of cardiovascular disease and mortality.
Forum member Skovenborg stated: “This is a well-done study with clear results that confirm previous study results in men. However, there are still some unanswered questions:
(1) Why does this relative modest amount of alcohol raise the blood pressure?
(2) What explains the difference in alcohol’s effect on night and day blood pressure?
(3) Can the results of a 4 week intervention study be extended to a regular intake of alcohol for years?” (This latter concern was echoed by reviewers Svilaas and Barrett-Connor.)
Reviewer Finkel agreed that “this is generally a well-done study of another of those confused/confusing relationships with wine or alcohol as the mover. I don’t know that we have a good explanation for the normal diurnal variation of blood pressure, so it is no surprise that drinking would have the differential effect that Skovenborg wonders about. The last sentence of the authors’ discussion (‘Our results provide no support for the concept that regular low-level alcohol intake can lower BP, suggesting that the J-shaped relationship between alcohol and BP in several studies is more likely because of the presence of unmeasured confounders’) strikes me as a bit egocentric. Given that some previous studies have reported a J-shaped BP response to drinking, maybe it depends on which factors are predominating in determining the BP.”
Reviewer Ellison had the same concern: “The authors emphasize that (1) higher level alcohol administration increases BP, which is shown by their data, but also conclude that (2) smaller amounts of alcohol (lower level) do not lower BP. The differences between low level red wine vs dealcoholized red wine are +0.4±0.6 mmHg for systolic and -0.3±0.4 mmHg for diastolic: these results are consistent with either a slight increase or a slight decrease in blood pressure. Overall, I do not believe that their data support their second conclusion.” Forum members Zhang, Djoussé, Barrett-Connor, and others agreed.
References from Forum critique
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.
Shai I, Wainstein J, Harman-Boehm I, Raz I, Fraser D, Rudich A, Stampfer MJ. Glycemic effects of moderate alcohol intake among patients with type 2 diabetes: a multicenter, randomized, clinical intervention trial. Diabetes Care 2007; 30:3011–3016. (NOTE: These authors have also recently reported at a conference similar outcomes in a much larger trial, the results of which are currently under review for publication).
The present paper describes the effects among 24 normotensive pre-menopausal women, all of whom were regular drinkers (of an average of 2 to 3 drinks/day), of the administration of two levels of alcohol in the form of red wine in a randomized clinical trial. Subjects were given low amounts of wine and higher amounts of wine during two 4-week intervention periods, with the effects on blood pressure compared with changes when subjects were given similar amounts of dealcoholized red wine. Subjects were divided into a “lower level” usual intake group who previously consumed < 200 g/week of alcohol and a “higher level” group who previously consumed >200 g/week.
Previous “lower level” drinkers were given two levels of alcohol, in the form of 100 ml/day of red wine on 4 days per week (an average of 46 g/week of alcohol, or the equivalent of about ½ typical drink per day) and 200 ml/day of red wine daily (about 146 g/week of alcohol, the equivalent of about 1 ½ to 2 typical drinks/day) for another 4-week period. Subjects who were previous “higher level” drinkers were given 100 ml of red wine daily (about 73 g/d of alcohol per week, the equivalent of about one typical drink/day) for 4 weeks and 300 ml/d of red wine (about 218 g/week of alcohol, the equivalent of about 2 to 3 typical drinks/day) for another 4 weeks.
The main results are a small but significant increase in 24-hour average blood pressure (+2.0 mmHg systolic and +1.3 mmHg diastolic) with higher levels of red wine but no significant effects (+0.4 mmHg systolic, -0.3 mmHg diastolic) from lower levels of red wine administration, when compared with blood pressure levels during periods when dealcoholized red wine was given. The differences were predominantly due to slightly higher awake rather than asleep blood pressures. These findings are similar to results of a limited number of randomized controlled trials of alcohol in men.
Forum members considered this to be a well-conducted clinical trial, with important results. There were, however, some concern that the study focused only on regular drinkers; results may have been different if previous abstainers had also been studied. Further, while the slight increase in blood pressure from higher levels of alcohol support previous research, the finding of no significant findings for lower levels of intake (when subjects were given the equivalent of between ½ and 1 drink/day) may not support what the authors suggest: “Our results provide no support for the concept that regular low-level alcohol intake can lower BP, suggesting that the J-shaped relationship between alcohol and BP in several studies is more likely because of the presence of unmeasured confounders.” Forum members considered their results to be consistent with either a slight increase or a slight decrease in blood pressure among such drinkers and are not necessarily inconsistent with data from some previous cohort studies that showed a “J-shaped” relation between alcohol and blood pressure.
A number of Forum reviewers also raised the question as to whether or not the results of a 4-week intervention study can be extended to the effects of the regular intake of alcohol for many years. Further, the fact that the study group included previous drinkers of up to similar amounts of alcohol as given during the higher intervention (yet were still normotensive) might suggest that their blood pressure was not “sensitive” to alcohol, and could limit the applicability of these results to the general public. Nevertheless, this intervention study provides important trial data on the short-term effects of alcohol on blood pressure.
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Note on Potential Conflict of Interest: One of the authors of this paper (Ian B. Puddey) is a member of the International Scientific Forum on Alcohol Research. Professor Puddey had no input into the preparation of this critique.
Comments on this critique by the International Scientific Forum on Alcohol Research were provided by the following members:
Elizabeth Barrett-Connor, MD, Distinguished Professor, Division of Epidemiology, Department of Family Medicine and Public Health and Department of Medicine, University of California, San Diego, La Jolla, CA USA
Giovanni de Gaetano, MD, PhD, Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo NEUROMED, Pozzilli, Italy
Luc Djoussé, MD, DSc, Dept. of Medicine, Division of Aging, Brigham & Women’s Hospital and Harvard Medical School, Boston, MA, USA
R. Curtis Ellison, MD. Section of Preventive Medicine & Epidemiology, Department of Medicine, Boston University School of Medicine, Boston, MA, USA
Harvey Finkel, MD, Hematology/Oncology, Boston University Medical Center, Boston, MA, USA
Dominique Lanzmann-Petithory, MD, PhD, Nutrition/Cardiology, Praticien Hospitalier Hopital Emile Roux, Paris France
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
Yuqing Zhang, MD, DSc, Clinical Epidemiology, Boston University School of Medicine, Boston, MA, USA