Scientists say they now have more "smoking gun" proof that cigarettes cause heart disease - the killer atop medicine's "Most Wanted" list.

In the current issue of the Journal of the American Medical Association, doctors unveiled the most damning evidence yet linking tobacco to ischemic heart disease - a weakening of the heart caused by episodic reduced blood flow to the pump.Such heart diseases are the leading cause of death and illness in the United States, claiming 500,000 lives per year. Scientists have long had statistical evidence linking cigarettes to heart disease and estimate that tobacco is responsible for 160,000, or about one third, of the deaths each year.

"This association has been confirmed by one epidemiologic survey after another, but what is lacking are smoking guns, direct connections between cigarettes and cardiac pathophysiology," wrote Dr. Peter Cohn in a commentary that accompanied the research article. Cohn is a physician at the State University of New York Health Sciences Center in Stony Brook.

Eight researchers, led by Joan Barry of Brigham and Women's Hospital at Harvard Medical School, compared 24 heart patients who smoked to 41 who did not. The patients all had stable angina pectoris, or chest pain symptomatic of the heart's failure to get enough oxygen.

The team studied the patients by monitoring their hearts for 24 hours or longer with a portable boxlike device, called the Holter monitor, that patients could wear as they pursued their daily activities.

During 4,968 hours of monitoring, the researchers detected 975 episodes of restricted blood flow to the heart. Only 8 percent of them were felt by the patients, who were asked to keep a log book of their activities and chest pains.

On average, the researchers reported, smokers had 3 ischemic episodes per day while non-smokers had just one. Each event lasted about 24 minutes for smokers, just 2 minutes for non-smokers."