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September 3, 2002

Can An Aspirin A Day Keep Atherosclerosis At Bay? Research Yields Another Benefit to Low-Dose Aspirin

(Philadelphia, PA) - The original miracle drug, aspirin, continues to surprise medical scientists. While studies have proven that aspirin can prevent a second heart attack by thinning the blood, researchers at the University of Pennsylvania School of Medicine have shown that aspirin can also prevent heart attacks and stroke through an entirely different mechanism. Using laboratory models, the Penn researchers demonstrated that aspirin also lessens the inflammation associated with atherosclerosis and stabilizes athersclerotic plaque. Their findings are presented in the current issue of Circulation.

"The past decade has seen a lot of research indicating that atherosclerosis is a chronic inflammatory disease," said Domenico Praticò, MD, assistant professor in Penn's Department of Pharmacology. "Our findings show that aspirin not only decreases inflammation in the arteries and the growth of the atherosclerotic plaque, but it also beneficially alters the consistency of the plaque that remains."

Atherosclerosis, also known as hardening of the arteries, is a main cause of heart attacks and strokes, two leading causes of death in the United States. A variety of factors, including genetics and diet, spur the disease, which occurs as cholesterol-rich cells of the immune system accumulate inside of blood vessels. As these plaques grow, they cause the blood vessels to narrow. If a portion of the plaque breaks off it can induce the formation of a thrombus, a blood clot that could completely obstruct blood flow and cause a heart attack. Likewise, a portion of the thrombus could also travel through the bloodstream to the brain, where it could cause a stroke.

The Penn researchers found that low-dose aspirin leads to a change in the composition of the plaque, turning it from a soft foamy material to a harder material that is less likely to rupture.

"After aspirin, we find more collagen and smooth muscle cells in arterial plaque and significantly less cholesterol-rich cells," said Praticò. "Of course, it is better to have no plaque at all, but if you have plaque in your arteries, you would prefer it to stay put - where it will do the least harm."

Although the exact causes of atherosclerosis are unclear, researchers have known that the inflammation found in atherosclerosis is associated with increased levels of cellular inflammatory signals called cytokines. Plaque formation is also associated with increased levels in the aorta of a protein called NF-?B that controls the formation of these cytokines, stimulates the growth of immune cells and the accumulation of low-density lipoproteins (LDL) - also known as the 'bad' cholesterol. The Penn researchers have found that aspirin lowers the amount of both cytokines in the blood stream and the NF-?B in the aorta, suggesting a potent anti-inflammatory action of the drug.

Praticò and his colleagues hypothesize that these novel effects of low-dose of aspirin are independent from its known function as blood thinner.

Aspirin directly inhibits the cycloxygenase (COX) enzyme, which allows platelets in the blood to form clots. After aspirin blocks COX, it enables this enzyme to produce powerful anti-inflammatory molecules such as lipoxins, which in turn could inhibit the formation of cytokines - the very molecules that may stimulate atherosclerosis.

While Praticò recognizes more research needs to be done, aspirin could provide a potent, and inexpensive way to fight atherosclerosis. Low-dose aspirin has already been proven effective in preventing a second heart attack. There is a danger, however, taking large doses of aspirin, which can lead to gastrointestinal bleeding.

So, what constitutes a low-dose?

"Generally, we consider between 80mg and 250mg of aspirin to be 'low-dosages' - about the amount you would find in children's aspirin," said Praticò. "Of course, anyone considering taking a regimen of low-dose aspirin should consult a physician first."

The research detailed in this study was supported by grants from the American Heart Association and the National Institutes of Health.


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