Effect of Reduced Alcohol Consumption on
Blood Pressure in Untreated Hypertensive Men
Hirotsugu Ueshima, Kazuo Mikawa, Shunroku Baba, Satoshi Sasaki, Hideki Ozawa, Motoo Tsushima, Akito Kawaguchi, Teruo Omae, Yoshiaki Katayama,
Yuzo Kayamori, and Keiichi Ito
Fifty-four untreated, mildly hypertensive men whose daily alcohol consumption was £28 ml ethanol and who drank at least 4 times per week took part in a randomized, controlled crossover trial. The purpose of the trial was to test the effects of alcohol reduction on blood pressure. After a 2-week familiarization period, the participants were assigned to either a reduced alcohol drinking group or a usual drinking group for 3 weeks (experimental period 1). The situation was then reversed for the next 3 weeks (experimental period 2). The participants were requested to limit their daily alcohol consumption to zero or reduce it as much as possible for the reduced alcohol consumption period. The self-reported alcohol consumption was 56.1 ±3.6 (SEM) ml/day during the usual alcohol drinking period and 26.1 ±3.0 ml/day during the period of reduced alcohol consumption. Systolic and diastolic blood pressures in the intervention group were found by analysis of variance to be significantly lower (2.6-4.8 and 2.2-3.0 mm Hg, respectively) than those in the control group during experimental period 2 for systolic blood pressure and experimental period 1 for diastolic blood pressure. Significant (3.6 mm Hg) and nonsignif-icant (1.9 mm Hg) decreases in systolic and diastolic blood pressure, respectively, were observed. The method of Hills and Armitage was used, reducing ethanol in daily alcohol consumption by 28 ml. The lowering effect of reduced alcohol consumption on blood pressure was independent of changes in salt consumption, which were estimated by 24-hour urine collection and body weight. It was concluded that a reduction in daily alcohol drinking of ethanol from 56 ml to half that amount was feasible and effective in lowering blood pressure for nontreated mildly hypertensive patients who regularly consume alcohol. (Hypertension 1993;21:248-252)
KEY WORDS • alcohol drinking • blood pressure • antihypertensive therapy, nonpharmacological • hypertension, mild
M
any cross-sectional epidemiological studies have demonstrated that alcohol consump-tion is closely related to blood pressure levels and to the prevalence of hypertension.1"15 The association seems to be one of cause and effect since it persists even after many confounding factors are taken into consideration. 1.6.9.11-13 Several controlled trials for hypertensive patients receiving medication and for nor-motensive subjects found support for the observation that alcohol has a pressor effect and that a reduction in alcohol consumption lowers blood pressure.16"23 How-ever, it still remains to be seen whether a reduction in daily alcohol consumption in mildly hypertensivepa-From the Department of Health Science (H.U., K.M., S.S.), Shiga University of Medical Science, Otsu, the Department of Public Health (K.M., S.S.), Osaka University Medical School, the National Cardiovascular Center (S.B., M.T., A.K., T.O., Y. Katayama, Y. Kayamori), the Department of Public Health and Hygiene (H.O.), Medical College of Oita, and the Yohkaichi National Hospital (K.I.) (Japan).
Supported in part by research grant 60-6A for cardiovascular diseases from Japan's Ministry of Health and Welfare.
Address for correspondence: Prof. Hirotsugu Ueshima, MD, Department of Health Science, Shiga University of Medical Science, Tsukinowa-cho Seta, Otsu, Shiga 520-21, Japan.
Received June 9, 1992; accepted in revised form October 13, 1992.
tients who are not taking medication but who have alcohol-drinking habits is an effective means to decrease blood pressure. Accordingly, we carried out a random-ized, crossover controlled study to further test the effects on blood pressure of a reduction in daily alcohol consumption in untreated, mildly hypertensive, male office workers.
Methods
Male volunteers, aged 30-59 years, were recruited from their workplace by public health nurses. The volunteers were civil servants with systolic blood pres-sure >140 mm Hg, diastolic blood prespres-sures >90 mm Hg, or both, as measured during annual health check-ups. These volunteers also consumed alcohol daily and thus were classified as having drinking habits. Volunteers whose systolic and diastolic blood pres-sures were between 140 and 179 or 90 and 109 mm Hg, respectively, were eligible for the intervention study, whereas those who were taking antihypertensive medi-cation at the time of the first screening examination were excluded. With regards to drinking habits, only volunteers who consumed more than 28 ml ethanol at least 4 times per week were included in the study. Patients who needed treatment for conditions such as overt diabetes mellitus, hypercholesterolemia, and gout
Height 24hr Urine 24hr Urine 24hr Urine Weight Weight Weight Weight Weight Weight weight Weight Weight
Blood Blood Blood Blood
«• » li- «• BP 0 BP U BP BP 11 BP BP » BP 8P 0. BP Group B(27) Group A(27) Usual Alcohol Baseline 2 Weeks
Usual Alcohol | Reduced Alcohol
Reduced Alcohol Period 1 3 Weeks Usual Alcohol Period II 3 Weeks Drinking Record
FIGURE 1. Schematic shows design for a randomized,
con-trolled crossover study testing the effects of a reduction in daily alcohol consumption on blood pressure (BP) in 54 mildly hypertensive men who were not taking any medication and who regularly drank alcohol. BP and body weight were measured every week. Blood was drawn at the initial exami-nation, during the last week of the familiarization period, and during the last week of each experimental period. Daily alcohol consumption was recorded during the study period.
were excluded from this study. Only six people refused to participate. After screening, 54 of the 93 volunteers were found to satisfy the criteria for inclusion in the study; accordingly they were asked to give their in-formed consent. None had ever received antihyperten-sive medication, and all 54 volunteers completed the study.
Participants were randomly assigned to either group A or B. Group A members were asked to reduce their daily alcohol consumption as much as possible for the first 3 weeks of the experimental period (period 1), and group B was told to maintain its usual alcohol consump-tion. The situation was reversed for the next 3 weeks (experimental period 2). Blood pressure was measured twice during the day (between 10 AM and 3 PM) using a Random-Zero sphygmomanometer (Hawksley and Sons Ltd., Lancing, UK) with participants in the sitting position. The doctor performing the blood pressure measurements was blinded concerning the treatment phase of the participants. Before blood pressure mea-surements were taken, each participant was allowed a 5-minute rest period after ensuring that he had re-frained from eating, smoking, and strenuous exercise during the previous half hour.
Figure 1 shows the detailed design for the random-ized, crossover controlled study. Blood pressure was measured weekly; that is, three times during the 2-week baseline period and once weekly during each 3-week experimental period. Body weight was also measured weekly. Blood chemical analyses were done twice during the baseline period and once during each experimental period. A 24-hour urine collection was done during the baseline period and during each experimental period to measure sodium and potassium excretion. The partici-pants were asked to record their daily alcohol consump-tion. This record was checked by public health nurses every week during the entire study period of 2 months. A sample calculation was done based on the results of the previous study21 in an attempt to detect an 8-mm Hg difference in systolic blood pressure between the two
groups. Twenty-seven participants for one group were needed to detect a significant difference that occurred at a=0.05 and at /3=0.10. Therefore, the power to detect the difference (1-/3) was 90% in this study. Significance tests for selected variables, including sys-tolic blood pressure, were done separately on the two groups during periods 1 and 2. Changes in selected variables, including blood pressure changes from the last baseline measurement were compared separately for the two groups by analysis of variance during periods 1 and 2. The treatment effect, combining all participants for the two experimental periods and taking into ac-count all but the urine and blood chemical data for the last 2 weeks, was then calculated using the method of Hills and Armitage.24 This method was applied to the two-period, crossover controlled study. A two-sided test was done at a=0.05.
Results
Table 1 shows a comparison of the baseline data for both groups. Age, height, body mass index, systolic and diastolic blood pressure, and pulse rate were not signif-icantly different between the two groups, although the systolic blood pressure of group B was slightly higher than that of group A. Daily alcohol consumption and its biochemical markers, such as high density lipoprotein (HDL) cholesterol, y-glutamyltranspeptidase (y-GTP), and uric acid, were not significantly different during the baseline period. Most of the alcohol consumed here was in the form of beer, "sake" (Japanese traditional alco-holic drink), and whiskey. Smoking habits and sodium and potassium excretion in 24-hour urine collection were not significantly different.
The request to reduce alcohol for the first 3 weeks (experimental period 1) of the study was well accepted by participants in group A. Similarly, the request to maintain usual alcohol consumption for the same period was accepted by group B participants (Figure 2). The situation was then reversed for the next 3-week period. Groups A and B were compared with respect to changes from baseline in systolic blood pressure. The systolic blood pressure of the subjects in group A, who reduced alcohol consumption to half, showed a large decline compared with that of group B during period 1 (Figure 3). In period 2, the systolic blood pressure of subjects in group A, who returned to their usual drinking habits, increased somewhat, whereas the systolic blood pressure of those in group B, who reduced alcohol consumption, declined further from the level of the control period when usual alcohol drinking resumed. The 2.6-4.8 mm Hg difference in systolic blood pressure between the two groups in period 2 was significant by analysis of variance (Figure 3). Similarly, the 2.2-3.0 mm Hg difference in diastolic blood pressure between the two groups during period 1 was significant (Figure 4).
Further analysis was done using the method of Hills and Armitage24 to detect a treatment effect. Table 2 shows the changes in alcohol consumption and its biochemical markers after combining both groups. Al-cohol consumption during the treatment period was found to be half that of the amount consumed in either the baseline or control period. Biochemical markers of alcohol consumption, such as y-GTP and HDL
choles-TABLE 1. A Comparison Between the Baseline Data of Group A and Group B in a Randomized, Controlled Crossover Trial for Mildly Hypertensive Men Not Taking Any Medication
Variables Age (years) Height (cm) Weight (kg) BMI (kg/m2) SBP (mm Hg) DBP (mm Hg) Pulse (bpm)
Alcohol (ethanol, ml/day) Cigarette smoking (No./day) Smoking rate (%)
HDL cholesterol (mmol/L) 7-GTP (units/L)
Uric acid (mmol/L) Sodium (mmol/day) Potassium (mmol/day) Group A (II=27) 43.3 (7.8) 165.7 (5.6) 67.7 (7.6) 24.6 (1.9) 141.7 (13.7) 95.6 (9.7) 74.2 (9.2) 61.6(30.5) 13.0 (17.6) 44.4 1.32 (0.38) 122.5 (94.8) 387.8 (74.9) 212.0(38.1) 46.6(11.3) Group B (n=27) 45.0 (7.6) 167.6 (6.5) 67.6 (6.6) 24.1(2.1) 146.1 (12.3) 97.2 (7.8) 76.6 (9.6) 51.7(19.6) 16.3 (18.2) 55.6 1.22(0.21) 111.1 (97.1) 365.2 (83.8) 201.8(56.4) 44.5 (13.2) P NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS Values are mean (±SD). BMI, body mass index (weight/height2 [kg/m2]); SBP, systolic blood pressure; DBP, diastolic blood pressure; bpm, beats per minute; HDL, high density lipoprotein; y-GTP, •y-glutamyltranspeptidase. With the exception of the smoking rate for which a x2 t e s t w a s done, t tests were used to compare between-group variables.
terol, changed simultaneously with reported alcohol consumption (Table 2). These changes were significant. The treatment effect of alcohol consumption reduc-tion on blood pressure was also assessed using the Hills and Armitage24 method (Table 2). The decrease of 3.6 mm Hg in systolic blood pressure was significant, but the drop of 1.9 mm Hg in diastolic blood pressure was not. Body weight, pulse rate, and sodium and potassium excretion did not change significantly during either of the experimental periods. The treatment-period inter-action was also tested using the Hills and Armitage24 method; however, it was not significant even for blood pressure and alcohol consumption.
Discussion
A reduction in daily alcohol consumption to half was observed to significantly lower the blood pressure of mildly hypertensive men without the aid of antihyper-tensive medication. The present study was done under
Group B (27) Group A (27) 51.7ml 61.6 1st 2nd Baseline 58.0 26.6 1st 60.2 59.2 29.9 33.9 2nd 3rd Period 1 24.1 S3.8 1st 22.2 | 55.2 2nd 18.7 | 50.5 3rd Week Period 1
FIGURE 2. Bar graph shows average daily alcohol
consump-tion (ethanol in milliliters per day per capita) for groups A and B during the familiarization baseline period and during experimental periods 1 and 2 in a randomized, controlled crossover trial. Daily alcohol consumption was calculated for the 2-week familiarization period and for each week during experimental periods 1 and 2.
normal working conditions. Most participants were compliant when asked to reduce or discontinue their daily alcohol consumption as much as possible during the former or latter half of the 6-week experimental period. Thus, the results suggest that it is feasible to reduce daily alcohol consumption to half and that a reduction in alcohol consumption in daily life may lower blood pressure significantly.
The differences between the two groups in systolic blood pressure during period 2 and in diastolic blood pressure during period 1 were 2.6-4.8 and 2.2-3.0 mm Hg, respectively. The decrease in blood pressure
p<0.05
Baseline Period I Period I
FIGURE 3. Line graph shows changes in systolic blood
pressure (SBP) level with one standard error from the baseline on the last day of the familiarization period for groups A and B in a randomized, controlled crossover trial. Data were collected from 54 mildly hypertensive men who regularly drank alcohol and were not taking any medication. In period 2, SBP was significantly lower (2.6-4.8 mm Hg) in group B, the reduced alcohol consumption group, than in group A, the usual drinking group. Significance test was done by analysis of variance.
Baseline Period I Period I
FIGURE 4. Line graph shows changes in diastolic blood
pressure (DBP) level with one standard error from baseline on the last day of the familiarization period for groups A and B in a randomized, controlled crossover trial. Data were col-lected from 54 mildly -hypertensive men who drank alcohol regularly and were not taking any medication. In period 1, DBP was significantly lower (2.2-3.0 mm Hg) in group A, the reduced alcohol consumption group, than in group B, the usual drinking group. Significance test was done by analysis of variance.
resulting from a reduction in daily alcohol consumption by 30.0 ml was on average 3.6 mm Hg for systolic blood pressure and 1.9 mm Hg for diastolic blood pressure. This calculation was done using the treatment effect of Hills and Armitage.24 Based on this observation, it may be reasoned that a fall in systolic blood pressure of 5 mm Hg will result from the daily elimination of three drinks (42 ml ethanol). The volunteers who participated in this study were mildly hypertensive subjects who were not taking any medication. One large scale clinical trial for mild hypertension reported that participants as-signed to a /3-blocker treatment group lowered their systolic blood pressure by 10 mm Hg more than the control group.25 Therefore, the 5-mm Hg fall in systolic blood pressure, obtained by adjusting the daily alcohol consumption, is equivalent to half the effect of drug treatment. Puddey et al19 also observed approximately
the same magnitude of blood pressure decline, 5.0 and 3.0 mm Hg for systolic and diastolic blood pressure, respectively, after daily ethanol consumption was re-duced from 65 to 9 ml in mildly hypertensive subjects who were taking medication. In their study, however, the effect on blood pressure was observed within 2 weeks after reducing alcohol consumption. Other ran-domized controlled studies have also showed similar results.17-21-23
In the present study, the decline in diastolic blood pressure was not as clearly evident as the decline in systolic blood pressure. This may have been due to the absence of an increase in the effect on diastolic blood pressure during the usual drinking period and after the reduced alcohol drinking period; that is, the diastolic blood pressure in group A did not increase despite a return to usual drinking habits. The reason is not clear. The same observation was seen in a trial of normoten-sive men.18
Although many epidemiological and clinical studies support the cause-effect relation, the pressor mecha-nism of alcohol remains unknown.1 In Japan, salt has been suspected as a confounding factor in this relation because when Japanese people drink alcoholic bever-ages such as "sake" or beer they customarily eat salty foods.26 According to the 24-hour urine collection of this randomized controlled study, however, salt con-sumption was not reduced during the period of low alcohol consumption. Furthermore, this study showed that potassium excretions in 24-hour urine collection were quite stable. Therefore, it may be concluded that the depressive effect on blood pressure by reducing alcohol consumption is independent of changes in so-dium and potassium intake.
The INTERSALT study is a well-standardized, large-scale population survey on the relation between blood pressure and minerals in urine. This study has involved the examination of over 10,000 people in 52 population groups across 32 countries.27 In support of our findings, the INTERSALT study also showed that high alcohol consumption (150 ml/wk) was related to hypertension, independent of sodium and potassium excretion in 24-hour urine collection or body mass index (weight/
TABLE 2. Effect on Blood Pressure and Other Selected Variables for the Combined Groups (n=S4) in a Randomized, Controlled Crossover Trial Involving Treatment by a Reduction in Daily Alcohol Consumption
Variables
Alcohol (ethanol, mL/day) HDL cholesterol (mmol/L) y-GTP (units/L) SBP (mm Hg) DBP (mm Hg) Body weight (kg) Pulse rate (bpm) Sodium (mmol/day) Potassium (mmol/day) Baseline 56.7 (3.5) 1.27(0.04) 116.8(13.0) 143.9(1.8) 96.4(1.2) 67.7(1.0) 75.4(1.3) 206.9 (8.6) 45.5(1.7) Experimental phase Reduced alcohol 26.1 (3.0) 1.13 (0.04) 87.9 (9.2) 136.5(1.5) 91.0(1.0) 67.6 (0.9) 73.9(1.2) 227.4(10.3) 47.1 (2.0) Usual alcohol 56.1 (3.6) 1.21 (0.04) 101.0(11.0) 140.1 (1.3) 92.9 (0.9) 67.7 (0.9) 75.7(1.1) 220.6 (10.3) 47.1 (1.8) P <0.001 <0.01 <0.05 <0.05 NS NS NS NS NS Values are mean (±SD). HDL, high density lipoprotein; y-GTP, y-glutamyltranspeptidase; SBP, systolic blood pressure; DBP, diastolic blood pressure; bpm, beats per minute. The treatment effect was tested using the method of Hills and Armitage.24 Testing was done using data from the last 2 weeks in periods 1 and 2, but using the single data at the end of each experimental period for HDL cholesterol, y-GTP, sodium, and potassium.
height2, kg/m2).27 Since body weight did not change during the experimental period, we concluded that the fall in blood pressure was not related to weight change. Some epidemiological studies have revealed that there is a relation between pulse rate and blood pres-sure.28 However, except for the fact that in the period of reduced alcohol consumption, the pulse rate was 2 beats per minute lower than in the period of usual alcohol consumption, we did not find any dramatic changes in pulse rate. Thus, because of a lack of evidence, the exact nature of the pressor mechanism associated with alco-hol drinking and mediated by sympathetic nerve activity still remains unclear in the present study.
One limitation of the present study is the shortness of the intervention period. The long-term effect of re-duced daily alcohol consumption on blood pressure could not be assessed. However, from the results of many cross-sectional and prospective studies1"15 and a long-term intervention trial,22 it is reasonable to expect that mildly hypertensive patients can maintain the treat-ment effect of reduced daily alcohol intake on lowering blood pressure if reduction in daily alcohol consumption is continued. Furthermore, some intervention studies showed that advice to change to a beer with low alcohol content1819 or to reduce alcohol consumption21"23 would also be feasible and effective in lowering blood pressure. In conclusion, moderation of daily alcohol consump-tion as a nonpharmacological means of treatment under normal working conditions seems to be a feasible and effective method for lowering blood pressure in un-treated, mildly hypertensive patients who regularly drink alcohol. Because the effects of alcohol reduction on blood pressure levels may appear within 2 to 3 weeks,16"2123 patients who consume more than two drinks per day should be advised to reduce their alcohol intake.
Acknowledgments
We thank the four public health nurses (Hisae Sanada, Toshiko Yasuzuka, Naomi Teruya, and Yoko Yamamoto) for their efforts in recruiting volunteers, taking medical histories, and other important management aspects of this study, and Karen Kobayashi, MSc, for her thoughtful editorial assistance.
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