Regular Drinking Raises Blood Pressure, Meta-Analysis Affirms

BRISTOL, England, March 4 -- Even moderate alcohol intake over a lifetime may have a marked effect on blood pressure, researchers said.
Action Points
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• Explain to interested patients that the meta-analysis supported but does not prove a link between alcohol and blood pressure.
• Note that the studies in the meta-analysis included primarily Japanese men.

Men who averaged three drinks a day had more than twice the risk of hypertension as those who drank little, if at all, reported Sarah J. Lewis, Ph.D., of the University of Bristol, and colleagues online in Public Library of Science -- Medicine.
Men who had one drink a day were at 70% elevated risk, the researchers found.
Systolic and diastolic blood pressure was also elevated "to a much greater extent, even among moderate drinkers, than previously thought," they wrote.
Observational studies have generally found lower blood pressure with moderate alcohol intake compared with nonuse or heavy intake, but those studies had limited ability to control for diet, smoking, exercise, income, and reporting bias.
So to eliminate these sources of confounding, the investigators did a meta-analysis of studies that focused on genetic variations for the enzyme that removes alcohol from the body. "Analyzing individuals by genotype," they said, "is akin to a randomized controlled trial of different lifetime levels of alcohol intake."
While the aldehyde dehydrogenase 2 (ALDH2) genotype is not associated with confounding factors, people who inherit two copies of the ALDH2 *2*2 variant tend to drink little because their body does not efficiently metabolize alcohol and they become flushed and nauseated after drinking, the researchers said.
The meta-analysis included 10 studies reporting on associations between ALDH2 and hypertension or blood pressure. Most were cross-sectional; all were population-based.
The studies were mainly done in Japan, where the ALDH2 gene variant is common. One small study came from England.
As expected, the investigators found that alcohol intake was highest at around 20 to 30 g per day for men with the *1*1 genotype and lowest at 2 g or less per day for *2*2 homozygotes. Men with the *1*2 genotype had intermediate intake at 10 to 15 g per day on average.
Alcohol intake was minimal among the relatively few women included in the studies, "but studies showed trends in the same direction as men," the researchers said.
Smoking status, sex, and physical activity did not differ between genotype groups. Body mass index tended to be higher among men with the more common *1*1 genotype.
"As alcohol is an energy-dense macronutrient and has an appetite-enhancing effect," the researchers said, "it is likely that the increase in BMI among individuals with the *1*1 genotype is due to their increased alcohol consumption."
In the three studies that reported hypertension outcomes for a total of 4,219 participants, men who drank more were at higher risk.
Men with the *1*1 genotype had 2.42-fold higher risk than those with the *2*2 genotype (95% CI 1.66 to 3.55, P=0.0000048). Men with the *1*2 genotype had 1.72-fold higher risk than those with the *2*2 genotype (95% CI 1.17 to 2.52, P=0.006).
The same effect was seen in the five studies that reported blood pressure outcomes for a total of 7,658 participants.
Mean diastolic blood pressure was 3.95 mm Hg higher among men with the *1*1 genotype and 1.58 mm Hg higher among men with the *1*2 genotype compared with *2*2 homozygotes (P<0.00001 and P=0.016, respectively).
Mean systolic blood pressure was 7.44 mm Hg higher for men with the *1*1 genotype and 4.24 mm Hg higher among men with the *1*2 genotype compared with *2*2 homozygotes (P<0.00001 and P=0.00005, respectively).
Each gram per day of alcohol consumption was estimated to increase diastolic blood pressure 0.16 mm Hg (95% CI 0.11 to 0.21) and to raise systolic blood pressure 0.24 mm Hg (95% CI 0.16 to 0.32).
Although findings could have been caused by pleiotropic effects of ALDH2, "if either pleiotropic effects or confounding by linkage disequilibrium were operating, an effect on blood pressure would be seen in both sexes," they said.
Further large-scale studies are needed to confirm the findings, they noted.
The editors' summary pointed out that "although the Mendelian randomization approach [used by the investigators] avoids most of the confounding intrinsic to observational studies, it is possible that a gene near ALDH2 that has no effect on alcohol intake affects blood pressure, since genes are often inherited in blocks."
The editors also pointed out that in the U.S., one standard drink contains about 14 g of alcohol and in the U.K. 8 g. Recommended daily limits in these countries, they said, are 1-2 units and 3-4 units, respectively.