Can An Aspirin A Day Keep Atherosclerosis At Bay?

[Guest guest]

Source:   University Of Pennsylvania Medical Center

(http://www.med.upenn.edu/)

Date:   Posted 9/4/2002

Can An Aspirin A Day Keep Atherosclerosis At Bay?

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.