Clinical trials exploring the link are difficult to implement and have limited follow-up time.
The Bristol study, led by Dr Sarah Lewis of the University's Department of Social Medicine, took a different approach focused on people who have a mutation on a gene which affects their body's ability to eliminate alcohol.
Alcohol is initially metabolised to an intermediate compound, acetaldehyde, which is further metabolised and then eliminated from the body. The major enzyme responsible for this elimination is alcohol dehydrohenase 2 (ALDH2).
In some people, a genetic mutation leads to an inability to metabolize acetaldehyde and causes an accumulation of acetaldehyde after alcohol intake. This mutation is common in some Asian populations and results in facial flushing after consumption of alcohol coupled with intense nausea, drowsiness, headache and other unpleasant symptoms. People with this mutation therefore drink much less than those without it
The researchers looked at the ALDH2 genotype, comparing the blood pressure of those who have this mutation “ the *2 *2 genotype “ with those who do not “ the *1 *1 genotype.
The study found that individuals with the *1 *1 genotype, who had an alcohol intake of around 3 units per day, had strikingly higher blood pressure than those with the *2 *2 genotype, who tend to drink only very small amounts, or no alcohol.
Dr Lewis said: This study shows that alcohol intake may increase blood pressure to a much greater extent, even among moderate drinkers, than previously thought. Large-scale replication studies are required to confirm this finding and to improve the precision of our estimates.
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Atherosclerosis or hardening of the arteries" is a chronic disease in which high cholesterol levels coupled with inflammation lead to the build-up of fatty deposits, called plaque, on the inner walls of arteries. Eventually these plaques can limit blood flow, leading to angina, or they may rupture, resulting in blood clots that block arteries and cause heart attacks or strokes.
When the researchers fed an experimental drug that turns on PPAR delta to genetically altered mice that develop the characteristic plaques at an early age, especially when placed on a high-fat diet, mice developed 25 “30 percent fewer plaques. Further studies revealed that PPAR delta not only raises HDL levels but also suppresses the inflammatory response in the artery, dramatically slowing down lesion progression.
Barish and Evans also contributed to a related study, which was led by researchers at the University of California, Los Angeles and published in the same issue of PNAS. Using a different mouse model to mimic the development of atherosclerosis, the UCLA researchers detected an even more pronounced anti-inflammatory effect that slashed the number of aortic lesions by up to 70 percent.
While Barish, a clinically trained endocrinologist, cautions that extrapolating from mice to humans is inherently fraught with complications, he believes that drugs switching on PPAR delta have the potential to protect against obesity, insulin resistance and their associated cardiovascular risks.
The discovery that any orally active compound can delay the progression of heart disease is rare, and considering the importance of the problem, we are hopeful that this work can be quickly carried into the clinic, says Evans.
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