(The Los Angeles Daily News) -- Remember the old adage about an apple a day keeping the doctor away? Well, change that to an aspirin.

The inexpensive bottle of white pills found in just about every medicine cabinet in America isn't just for headaches. A daily aspirin is proving to be a powerful agent in preventing the top three killers in America - heart disease, stroke and cancer.

The chemical form of salicin, a compound found in willow bark, aspirin was initially developed in 1897 by a Bayer chemist looking to treat his father's arthritis. Willow bark, an herbal medicine for American Indians and the Chinese, has been used to treat pain and fever since the time of Hippocrates.

"For the longest time, aspirin has been referred to as the wonder drug," said Dr. Ken Murray, vice chair of the pharmacy committee at Providence St. Joseph's Medical Center in Burbank. "What's astonishing is that every year we find something else where aspirin is not only an effective treatment, but the preferred treatment."

Its preferential status has brought its share of honors. Aspirin traveled to the moon with Apollo 11 in 1969 and was inducted into the Smithsonian's pharmaceutical collection in 1999. Doctors marvel at its potency. But most people take aspirin so much for granted that they don't even consider it a drug.

"I'll ask people if they're taking any medications and they'll say no. Then I'll ask if they take aspirin and they'll say yes," Murray said.

Aspirin is considered a safe over-the-counter medication. But like all drugs, aspirin presents risks, including stomach irritation, gastrointestinal bleeding and brain hemorrhage. People who have kidney or liver trouble, asthma or uncontrolled hypertension should avoid aspirin.

"This is a therapy that, introduced now, would be a prescription medication," said Dr. Ben Ansell, director of primary care and the cardiovascular disease prevention program at UCLA. "There are thousands of cases of complications with aspirin -- ulcers and strokes. If we had a (new) drug that caused that, we'd have every Ralph Nader group up in arms."

For most people, aspirin's benefits far outweigh its risks, Ansell said. Its versatility and power continue to make headlines.

CANCER FIGHTER

Recent studies suggest regular aspirin use can have an impact on the risk of breast cancer and colorectal cancer.

In a study released in March, Dartmouth-Hitchcock Medical Center researchers found a moderate benefit from a low dose of aspirin in preventing polyps, growths that can turn into colorectal cancer. Patients who took 81 milligrams daily -- the equivalent of one baby aspirin -- reduced their risk of colon and rectal polyps by 19 percent. The drug had an even greater effect in reducing the risk of advanced colon lesions, decreasing the likelihood by 40 percent.

Then in April, the Women's Health Initiative announced that regular aspirin and ibuprofen use could cut breast cancer risk by as much as half. The pain reliever study is part of a large-scale, long-term study launched by the National Institutes of Health.

The pain reliever study involved 81,000 postmenopausal women. The large sample allowed researchers to consider a number of risk factors, including a family history of breast cancer, hormone replacement therapy use, being overweight and having a late first pregnancy. Over 10 years, women who took a standard 325-milligram aspirin a day reduced their risk by 22 percent. The ibuprofen results were even more spectacular. A standard 200-milligram ibuprofen pill dropped the risk by 49 percent. Baby aspirin and acetaminophen, the pain reliever used in Tylenol, provided no protection.

"We were able to look at individual compounds and at high-risk groups," said Dr. Randall Harris, professor of epidemiology at Ohio State University's College of Medicine and Public Health. "The results are very stable and very consistent. We really need to move ahead to clinical trials to firm up the dose and the duration of use."

Harris said aspirin and ibuprofen work as COX-2 inhibitors, while acetaminophen does not. COX-2 is believed to be the trigger gene for inflammation. Blocking inflammation halts critical steps in cancer development, Harris said. Other COX-2 inhibitors include the arthritis drugs Vioxx and Celebrex.

"In my opinion, the link between inflammation and cancer is becoming stronger and stronger," Harris said.

He suggests women over 40 consider taking aspirin or ibuprofen as a preventive measure. However, he notes that more research will be needed to determine if the protective benefits extend to premenopausal women.

TAKEN TO HEART

Researchers also are uncovering more evidence of aspirin's role in combating cardiovascular disease.

"Aspirin has one of the most profound effects on cardiovascular health of any medication we've studied," said Dr. Patricia Gum, an interventional cardiologist at the Cleveland Clinic in Ohio, noting that chewing an aspirin after a heart attack decreases the odds of dying by 40 percent. "We don't have other medications that show that dramatic a drop.

Though aspirin's effectiveness against cardiovascular disease was long attributed to blood thinning, the drug's strength may actually lie in its anti-inflammatory properties. Doctors now say high levels of inflammation in the body may be a better predictor for heart disease than cholesterol alone.

Research suggests that the fatty cholesterol deposits that line the blood vessels become inflamed. This inflammation can cause the deposit to burst, releasing a clot that could trigger a heart attack. A blood test for what's called C-reactive protein can measure the inflammation levels, Ansell said.

"When you take aspirin, you reduce the C-reactive protein," Ansell said. "While aspirin does have that blood-thinning or anti-platelet effect, the mechanism is probably more due to aspirin's reduction of inflammation of these plaques."

The relationship between aspirin and stroke is more complex, Ansell said. Aspirin helps to prevent nonbleeding strokes but raises the risk of less common hemorrhagic strokes.

Last year, the U.S. Preventive Services Task Force gave its strongest endorsement to low doses of aspirin for Americans considered at risk of coronary heart disease. More than 1 million Americans die of heart attacks and other forms of coronary heart disease each year.

The task force cited a 28 percent reduction in risk for those who had never suffered a heart attack or stroke but had factors that made them candidates. According to the recommendation, men over 40, postmenopausal women and people with other factors such as hypertension, diabetes and smoking, should discuss taking aspirin with their doctors.

ASPIRIN RESISTANCE

Then there are those who just don't respond to aspirin at all. Gum, the Cleveland Clinic cardiologist, released study results in March on aspirin resistance. Over two years, 24 percent of study participants with aspirin resistance died of a heart attack, compared to 10 percent of those who responded to aspirin.

In most people, aspirin keeps platelets in the blood vessels from clumping. In people with aspirin resistance, the platelets stick together anyway. The problem is people have no way of knowing whether they're resistant or not. The test Gum used on her study participants is only done at specialized medical facilities.

"Right now, we don't have a bedside test out there," Gum said. "There are people out there not getting this benefit from aspirin. It's important to identify these people and find another treatment."

Copyright 2003 The Los Angeles Daily News. All rights reserved.