Marathon running may trigger a cascade of potentially heart- damaging events, as reported by McLean Hospital researchers in back-to-back papers in the October 17 American Journal of Cardiology. Arthur Siegel, M.D., director of internal medicine at McLean, and his collaborators analyzed the blood of marathoners less than 24 hours after finishing a race and found abnormally high levels of inflammatory and clotting factors of the kind that are known to set the stage for heart attack.

"My concern is for people who exercise thinking 'more is better', and that marathon running will provide ultimate protection against heart disease," said Siegel. "In fact, it can set off a cascade of events that may transiently increase the risk for acute cardiac events."

Does that mean you should hang up your running shoes? "No, not at all. But it does mean we need to understand more about marathon training and how the human body reacts to stress," said Charles Schulman, M.D., president of The American Running Association. "I'm concerned that running a marathon has come to be viewed as a modern rite of passage. Dr. Siegel's research may lead us to conclude that running a marathon is not a panacea. In fact, coupled with poor or improper training, it could lead to consequences much more serious than just the usual running injury."

Few studies have defined the cardiac risks imposed by a 26- mile run on a person with a presumably healthy heart. However, it is known that there are diminishing returns from the benefits of exercise as intensity and duration are increased. What's more, other studies indicate that overtraining leads to decreases in immune function and increases your risk of disease.

Also troubling, Siegel and his colleagues found that early markers used to detect heart attack in the emergency room (creatine kinase-MB, considered the gold standard) produced positive results on the runners, none of whom displayed any cardiac symptoms, suggesting that the test is misleading for this group. Runners and their doctors need to be aware of this discrepancy.

"On the basis of early stage markers, runners can be overdiagnosed with heart attack," Siegel said. He believes the high levels of creatine kinase-MB -- and hence the false- positive result -- are released by injured skeletal muscle, rather than heart muscle in the runners. In contrast, cardiac troponins, as late-stage markers for heart attack, remained normal the day after the race.

To explore the cardiac risk of long-distance running, Siegel followed a group of 80 physicians who are members of the American Medical Athletic Association. The subjects, entrants in the 100th to 105th Boston Marathons, were on average 47 years old, had no reported history of smoking or coronary disease, and had run several prior marathons. At each of the five races, researchers drew blood three times -- the day before the race, within a few hours of finishing and the morning after the marathon.

Normally, blood maintains a balance of blood thickening factors - - inflammatory and clotting factors -- and blood thinning, or fibrinolytic, activity. Exercise is known to raise the levels of both types of factors. Siegel found that while the balance between thinners and thickeners was maintained in the blood of the marathoners before and just after the race, it was disrupted the morning after: fibrinolytic activity returned to normal, but clotting and inflammatory factors were elevated.

Despite the high levels, none of the subjects in the study collapsed or experienced an acute cardiac event during or after their races. Siegel believes that in addition to an increase in inflammatory and clotting factors, a second event -- such as a disrupted atherosclerotic plaque or a cardiac arrhythmia -- is needed to trigger a heart attack. "The rise in inflammatory and clotting factors loads and cocks the gun, but another complication needs to occur to pull the trigger during a marathon," he said.

"Sudden death during vigorous exercise is uncommon," added Schulman. "Most of those who die during exercise had pre- existing conditions that were augmented by the strenuous exercise."

"The benefits of an active lifestyle are tremendous," said Susan Kalish, executive director of the American Medical Athletic Association. "But Dr. Siegel's work shows that marathoning may have its risks. If your goal is to improve your health, go for a run...but perhaps don't train for a marathon. Leave the marathon to those whose goals are competition or for those who are dedicated to maintaining a more heightened level of serious training."

Investigators from the Massachusetts General Hospital (MGH) and Brigham and Women's Hospital in Boston collaborated on this research. McLean Hospital is the largest psychiatric teaching affiliate of Harvard Medical School, an affiliate of MGH and a member of Partners HealthCare System.

The American Medical Athletic Association is an association of running doctors and sports medicine professionals dedicated to promoting public health through physical fitness. It is the professional division of the American Running Association. For more information about heart health and running, see "Fitness Articles" at the American Medical Athletic Association and the American Running Association shared Web site: www.americanrunning.org.