DALLAS, July 14 -- Cigarette smoking causes subtle damage to blood vessels, which signals an early stage of heart disease that worsens as smoking continues, researchers report in today's Circulation: Journal of the American Heart Association.
Using a wide range of laboratory technologies -- from slushy ice water to positron emission tomography (PET) scanning -- researchers at the University of California at Los Angeles School of Medicine discovered that the blood vessels of smokers do not respond as well as those of nonsmokers when the heart needs more blood flow during physical exertion.
"The heart beats faster during physical exertion, requiring the coronary arteries to dilate or widen to increase the flow of oxygen-rich blood to the heart muscle to keep it pumping properly," explains Johannes Czernin, M.D., a co-author of the study.
The researchers, led by Roxana Campisi, M.D., found that the arteries of smokers don't dilate adequately, which can increase smokers' blood pressure and their risk for heart attack or stroke.
Smokers averaged about 14 percent less blood flow to the heart than nonsmokers when both groups underwent cold pressor testing, a brief exposure to ice water that stressed their hearts and caused them to beat faster. Blood flow was impaired even in smokers whose arteries were not obstructed by fat-filled plaque, says Czernin, associate professor of molecular and medical pharmacology/nuclear medicine at UCLA.
"The longer you smoke, the more abnormal the blood flow," he says. "That's something that needs more study. Now we want to know how long it takes after a person quits smoking before normal blood vessel function is regained."
The researchers found a loss of blood vessel function, but they can't explain how it happens. "The only thing we can prove here is that there is something abnormal in smokers' blood vessels even before they develop coronary artery disease," says Czernin.
Previous well-accepted research has shown that carbon monoxide, which is abundant in cigarette smoke, damages the endothelial cells that line the interior of blood vessels, Czernin says. Cigarette smoke also contains a number of cell-damaging toxins, and smoking increases the production of angiotensin II, which reduces activity of nitric oxide, a substance in the blood that instructs the blood vessels to expand.
Another factor that correlated with an abnormal blood flow in response to the cold pressor test was a low ratio of "good" cholesterol to "bad" cholesterol. HDL, or "good" cholesterol, is thought to clear the fatty substances from artery walls. The LDL, or "bad" cholesterol, enters the artery walls and contributes to the creation of the obstructions that impede blood flow to the heart.
The research is part of a larger project at UCLA directed by Heinrich R. Schelbert, M.D., and funded by the National Institutes of Health. The project seeks to find ways to detect coronary heart disease, the cause of heart attacks, in its very early stage and to improve the functioning of damaged hearts.
The study involved 33 healthy individuals without chest pain, shortness of breath, artery blockage, or any other evidence of coronary heart disease. They included 16 long-term smokers (13 males, 3 females), whose years of smoking ranged from 11 to 39 years, and 17 nonsmokers (10 males, 7 females).
None of the participants suffered from high blood pressure, diabetes mellitus, or genetic forms of high cholesterol. None were taking medications. The average levels of total and LDL cholesterol did not differ between the two groups, but average HDL cholesterol was lower among smokers. Two of the smokers and none of the nonsmokers had elevated blood levels cholesterol.
Each participant was injected with N-13 ammonia, a radioactive substance that allows researchers to visualize blood flow, and had a PET scan while resting. This was followed 45 minutes later by the cold pressor test in which the left hand was immersed in icy slush for 45 seconds. Then a second shot of N-13 ammonia was given and the exposure to the ice water continued for another minute as the PET scan recorded blood flow through the heart. Finally, to determine blood vessel dilation, each person received a four-minute infusion of the drug dipyridamole, which increases blood flow to the heart, followed by another injection of N-13 ammonia and further PET scanning.
Co-authors of the paper are Heliko Schöder, M.D.; James W. Sayre, Ph.D.; Fernando D. Marengo, Ph.D.; Michael E. Phelps, Ph.D.; and Heinrich R. Schelbert, M.D.
Materials provided by American Heart Association. Note: Content may be edited for style and length.
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