Doctors at the University of Maryland Medical Center had a mystery on their hands. A 51-year-old physician colleague who looked the picture of health—no cardiovascular risks, a marathon runner who had exercised vigorously each day for 30 years—had just flunked a calcium screening scan of his heart.

The patient had expected a score indicating a healthy cardiovascular system. Instead, the images indicated a high score: a build-up of calcium in his coronary arteries put him at high risk for blocked blood vessels and a possible heart attack.

The mystery was all the more intriguing because his resting blood pressure and fasting cholesterol levels, the usual measures of cardiovascular health, were in the normal range.

In the March 1, 2007, issue of the American Journal of Cardiology, the researchers say this is the first case, to their knowledge, of advanced coronary calcification in an otherwise healthy middle-aged male marathon runner who lacked traditional cardiac risk factors and had no symptoms of heart disease.

The researchers conclude that the physician’s intense, long-term exercise regime, coupled with a predisposition toward a type of hypertension, contributed to his cardiovascular disease. "In this particular individual, we think that oxidative stress was an important contributor," says the study’s senior author, Michael Miller, M.D., director of preventive cardiology at the University of Maryland Medical Center and associate professor of medicine at the University of Maryland School of Medicine. "But we also found that this individual has exercise-induced hypertension, which I think is vastly under-diagnosed."

Oxidative stress is a byproduct of the normal cellular metabolism of oxygen. It refers to cell, tissue or organ damage from a class of molecules associated with oxygen metabolism, including unstable molecules called "free radicals." Oxidative stress plays a role in many heart, lung, blood and sleep disorders, including atherosclerosis, or hardening of the arteries, hypertension, heart failure, asthma and sleep apnea.

To help gage the impact of oxidative stress on the patient’s cardiovascular system, his doctors evaluated the response to exercise of the endothelium, the lining of his arteries. An ultrasound device was used to measure what is known as flow-mediated vasodilation. It shows how well the endothelium responds to a sudden increase in the flow of blood through an artery in the upper arm. The endothelium in a healthy vessel typically dilates or expands during this test to accommodate the increased blood flow, while an impaired vessel constricts or narrows.

The patient's blood vessel dilation was normal before exercising. But after exercise, vessel constriction occurred immediately and showed no improvement after an hour. To put this response into perspective, the researchers administered the same exercise/blood vessel response test to a group of ten men whose mean age was 41. The vessels of these men initially constricted, but improved significantly one hour after exercise.

Several weeks later, the patient was given vitamins C and E just before exercise and was tested again for endothelial response. These vitamins are known as antioxidants and may protect cells from free radical damage. This time, the test revealed a partial reversal of the blood vessel constriction after one hour, and normalization after two hours.

"As he took the vitamin C and vitamin E, you could see improvements in his brachial arteries," says Dr. Miller. "We recommended that the patient take these vitamins before he runs."

With half the mystery solved, the research team explored another possible cause of the calcium buildup—elevated blood pressure. Hypertension can cause artery walls to thicken and the endothelium to narrow. This narrowing can promote the formation of fatty plaque deposits in artery walls. The plaque, from cholesterol and fats, can eventually harden or calcify.

Although hypertension did not seem to be a risk factor for this patient, exercise is a major factor in his life. So, the researchers turned to a treadmill stress test to measure his blood pressure during exercise. At the start of the treadmill test, his baseline blood pressure was normal, 118/78 millimeters of mercury (mmHg). He was in such great shape that it took 20 minutes to reach high blood pressure levels, and this happened only after the treadmill speed and incline had been raised. But by the end of the test, his blood pressure had soared to 230/78 mmHg. A check of several of his previous treadmill tests indicated a similar rise in blood pressure.

On the basis of running duration and intensity, the researchers estimated that the patient spent about 30 minutes a day at a systolic blood pressure above 200 mmHg. This number is well into the blood pressure danger zone and meets one definition of exercise-induced hypertension—a jump of at least 60 mmHg from baseline after exercise.

This finding should be investigated further, says co-investigator Matthew R. Weir, M.D., head of nephrology at the University of Maryland Medical Center and professor of medicine and head of the division of nephrology at the University of Maryland School of Medicine. “Because we know that blood pressure rises during a stress test, we tend not to pay attention to it. We’re more interested in changes in electrical activity and the redistribution of blood during exercise, which could indicate inadequate blood supply to the heart muscle,” says Dr. Weir. “The question

is, should we pay more attention to treadmill-induced changes in blood pressure as a means to identify people at risk for developing coronary artery disease?” Dr. Miller adds another question, "Should we screen all middle-aged individuals who want to participate in an exercise program to make sure they don’t have exercise-induced high blood pressure?"

Unlike cholesterol or triglyceride levels, blood pressure levels fluctuate dramatically throughout the day, depending on a variety of factors such as exercise, emotions and even the time of day. In light of that phenomenon, Dr. Weir says the study raises another issue. "This research indicates that we need a more dynamic measure of blood pressure to truly profile the risk of an individual. We’ve been using casual, at-rest office readings of blood pressure for more than 50 years. It’s not bad, but it’s not the answer." The treadmill is one way to gather a more dynamic measurement, but he says there’s an easier option. "It can even be done at home if you have a blood pressure cuff and someone who can take your blood pressure at peak exercise."

The patient in the study continues to run, but is now taking medications to lower both his cholesterol and blood pressure. Despite his exercise regime, he appears to be in the same boat as millions of Americans who do not exercise regularly. So, is too much exercise a bad thing? The physicians answer to the contrary. "We are not publishing this report to suggest in any way that people should not be exercising. Exercise has stood the test of time as being one of the best ways to modify cardiovascular risk," says Dr. Miller. “But what we’re looking at are improved detection methods for predicting those at risk. Exercise-induced high blood pressure may be a part of that.”