IN THIS STORY:
>The Minefield
>Untrained Experts
>The Bomb Squad
>Assembling The Bomb
>Diffusing the Bomb
>Sidebar: Reactive Protein

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Bob was fit, so when his buddy, John, suggested they both get checkups before their 100-mile weekend bike trip, he protested. He was in better shape at 52 then he had been at 32. Nonetheless, he acquiesced, returned from the doctor, and proudly announced his low cholesterol, low blood pressure, and treadmill stress test confirmed he had the heart of a thirty-something man.

Ten miles into their ride, Bob complained that John was too slow, so they agreed to go at their own pace and meet up at the end of the day. John was surprised when Bob was not at the appointed place. He'd expected him to be waiting. When two hours past, John went looking for Bob and found him lying in the road not far from where they had parted company. He knew he was dead before he reached him.

When 57-year-old Frank retired, his gift to himself was to go climb a mountain in South America. A slender vegetarian whose activities included biking, hiking, and mountain climbing, he thought having his heart checked out was unnecessary, but the responsibility of a still-young family prompted him to err on the side of caution. He had a complete workup, including an electrocardiogram (EKG). The results were fine, and Frank was commended on his fitness. His climbing partners say he yelled, "My heart!" before he collapsed. At his funeral, his 10-year-old daughter had to be supported down the aisle, while his wife, holding their new daughter, greeted every one with, "This isn't possible."

In both cases, the coroner says hospital care would not have made a difference. The arterial wall exploded, completely blocking the artery, and both men died almost instantly. 

Are these cases flukes? Surprisingly, the answer is no. 

The Minefield

"This happens to a lot of people," says Dr. Prediman Krishan Shah, M.D., chief of cardiology at Cedars-Sinai Medical Center in Los Angeles, Calif., and director of the Atherosclerosis Research Center and a professor of medicine at the University of California Los Angeles School of Medicine. "They go to the doctor, the doctor looks at their cholesterol, it is normal. He looks at their blood pressure, it is normal. He does an EKG, it is normal…they put them on a treadmill, the treadmill is normal…they go and do physical activity, and they drop dead."

Almost 300,000 people each year die from sudden cardiac death (SCD), the term given to a fatal heart attack where the attack itself is the first sign of heart disease. This means more than one-half of heart attacks are striking victims with no obvious risk factors. 

SCD is much more likely to strike men than women and at a younger age. With this in mind, a European study looked at men who died between the ages of 35 and 62. Two-thirds of men who had SCD had no known risk factors. Nonetheless, a simple blood test would have revealed hidden heart disease. Had Bob and Frank requested this $25 blood test, they would have discovered that they were walking time bombs.

How, then, could they have left the doctor's office with a clean bill of health?

Untrained Experts

"Most internists and even cardiologists know very little about blood vessel and vascular disease," states Dr. John Cooke, M.D., director of vascular medicine at Stanford University in Stanford, Calif. "They are taught that eating fat clogs the arteries, which then must be unclogged…but atherosclerosis is not a plumbing problem. It is an inflammatory disease." 

Bob and Frank's doctors performed standard tests that look for clogs that can impair blood flow. However, Bob and Frank didn't have narrowed arteries. They had inflamed arteries pocked with plaques. These plaques account for two-thirds of heart disease and are undetectable by standard tests. These gooey, sticky ulcerations have a hard cap on them that can fracture in response to inflammation or exercise. During strenuous activity, for example, the artery expands to accommodate greater blood flow, which can break this protective seal. 

"A plaque can remain hidden in the wall of the artery and not cause a narrowing," says Shah. "And then that plaque that's hidden in the wall can burst, a blood clot forms, and the artery can go from not being narrowed at all to being completely occluded within a matter of seconds."

The Bomb Squad

The real experts are topflight cardiologists and research scientists who have spent the past 15 years in the lab building a new model of heart disease, identifying a simple test to detect it, and drafting new recommendations for prevention. At the lead is Dr. Paul Ridker, M.D., director for cardiovascular disease prevention at Harvard Medical School in Boston, Mass. 

"Inflammation weakens plaques, making it vulnerable to rupture," says Ridker. "Even a small burst plaque can trigger the formation of a clot and a heart attack. Many people with no outward signs of anything wrong have high levels of internal inflammation. It is exactly the same process that causes swelling and redness during infections or allergic reactions."

This is why other infections in the body, such as like gum disease, can contribute to a heart attack. It is also why diabetics, who have chronic widespread inflammation, are so prone to severe heart disease. While inflammation of the arterial wall is more serious, inflammation from any source can bombard plaque with harmful chemicals, weakening the cap. 

Ridker believes testing for inflammation should be the standard now. The highly sensitive C-Reactive Protein (CRP) test already is available, and it's inexpensive. The CRP test measures a blood protein that rises in response to inflammation. An elevated CRP of 2 milligrams per liter or higher indicates inflammation in the body.

While CRP is considered a marker for heart disease, new research reveals the protein itself is destructive (see the sidebar for more on CRP). 

"CRP, until now, was thought of as an 'innocent bystander' in the formation of heart disease, but it is, in fact, a key culprit that causes inflammation in the arteries, resulting in formation of clots and plaque that lead to heart attacks and strokes," said Dr. Ishwarlal Jialal, M.D., professor of pathology and director of the Laboratory for Atherosclerosis and Metabolic Research at the University of California Davis School of Medicine in Davis, Calif.

If a doctor determines you have elevated CRP, what should be done next? Some doctors will look for plaques. This is done indirectly with another test called an electron beam computed tomography (EBCT) scan. The scan identifies calcium deposits in the arteries, which are indicative of arterial plaques. 

However, some experts do not believe the EBCT scan is necessary, including Ridker.

"Once we reach middle age most of us have plaque in our arteries," says Ridker. 

The important question, then, is how stable are those plaques? The CRP test itself tells you if you are at risk. The higher it is, the more unstable the plaque. 

Shah disagrees. He believes the EBCT scan to be a great motivator for change. 

"I use the CT scan frequently to motivate individuals to modify their behavior," he says. "They see the picture. It's real to them. They change."

The experts have reached one consensus, however, and that's good news. By creating a new model for heart disease, they've helped answer the question about why so many people die suddenly from heart attacks, and they've given us a much better understanding of how to treat and prevent heart disease at an earlier stage.

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