Predicting Heart Disease

Beyond Cholesterol

From the Editors of The Berkeley Wellness Letter

October, 2004

This is the first in a series of special reports on women and heart disease from the editors of The Berkeley Wellness Letter.

An important new study on evaluating the risk of heart disease recently appeared amid much publicity in The New England Journal of Medicine. Dr. Paul Ridker and his associates at Harvard have found that an old test may have a new use -- it may predict heart disease in ways that blood cholesterol tests cannot.

What the blood test measures is called C reactive protein, or CRP. (Yes, another medical acronym - not what we most needed in the world - and it is not to be confused with CPR, which is cardio-pulmonary resuscitation.) CRP is produced by the liver in response to inflammation, now recognized as an important player in heart disease. Elevated levels of CRP are linked to an increased risk for heart attack and stroke, and possibly Type 2 diabetes. A person can have no outward signs of inflammation but still have "subtle" inflammation and, hence, an elevated CRP.

Should you ask your doctor for the test? Before you make up your mind, you need to know the background. Indeed, your doctor may be studying the background now, too. Cardiovascular disease is the No. 1 killer of Americans and Canadians and a major killer in most countries. You may think there are already enough ways to predict heart attacks. The risk factors are well-known: smoking, a sedentary life, obesity, diabetes, uncontrolled high blood pressure, a strong family history of the disease, increasing age, high levels of LDL ("bad") cholesterol, and low levels of HDL ("good") cholesterol.

But the troubling fact is that half of all people who have heart disease donot have elevated cholesterol levels. And 25 percent who have heart attacks have no identifiable risk factors at all. That's why scientists have been searching persistently for something else, and with CRP they may well have found one of the missing pieces.

The inflammation connection

For years the conventional thinking was that heart disease is simply a problem with the plumbing; blood vessels get clogged with fatty deposits called plaque, and eventually a blood clot comes along and shuts down the passageways to the heart, which results in a heart attack. And then a good surgical cleaning of the pipes is in order, along with medication to keep cholesterol and blood pressure down and the pipes open. Still, it has been known for at least a decade that matters are far more complex than that.

Actually, plaque does not form primarily on the inside walls of the blood vessels, but within those walls. Your arteries are nothing like pipes inside which blood cholesterol is passively deposited; blood vessels are made of very active tissue that changes all the time. Plaque results from the uptake of cholesterol from the blood by the vessel walls, as well as the buildup of cells and other material that can provoke an inflammatory reaction. Many things, such as smoking and high blood pressure, can further damage the vessel and aggravate inflammation.

When inflammation sets in, other cells enter the plaque, and it can grow further. As it grows, it bulges inward, narrowing the passageway and restricting the amount of blood the vessel can carry. But the greatest danger is if this plaque ruptures - and inflammation may trigger the rupture, as well. A ruptured plaque can in turn trigger a blood clot. If this clot is large enough or breaks off, it can block the passage of oxygen carrying-blood. Without oxygen the cells will die. If this happens in the heart, it's a heart attack; if it happens in the brain, it's a stroke.

What gets inflammation going in the first place? Bacterial infections have been blamed-in a 1999 article we cited Chlamydia as a possible culprit. But it may not be an outside agent at all. Indeed, the CRP that is the marker for inflammation may also help cause the trouble. Obesity plays a role in the process; fat cells may actually release chemicals that cause inflammation. High LDL and low HDL certainly do their dirty work. High blood pressure and smoking damage the vessel walls, as we've said. Like heart disease itself, plaque formation has many causes.

Some take-home messages

The blood test for CRP is easy to do and costs less than $50. But Dr. Ridker and his team do not recommend universal testing (even though he shares the patent to this CRP test). In January the American Heart Association and the Centers for Disease Control and Prevention published preliminary guidelines about CRP, recommending only limited use of the test. Even if you do take the test and discover that your CRP is elevated, there are no new treatments - no pill designed specifically to lower CRP. Researchers are currently studying whether people with normal LDL cholesterol but high CRP levels might benefit from taking a cholesterol-lowering statin drug.

Another problem: CRP rises for many reasons; even something as simple as a common cold can boost it. Researchers are still trying to determine if this test will be specific enough to diagnose cardiovascular disease in everybody.

There's a lot that can be done with or without a test. Here's a summary:

• The benefits of aspirin were discovered long ago, but its ability to quell inflammation and prevent clots has been most emphasized. Strong data show that low-dose aspirin therapy protects against heart attacks and, in some people, mini-strokes.
• Cholesterol-lowering drugs are highly recommended for those who need them. There's some evidence that statins help control inflammation and may lower CRP.
• There's evidence that people with high blood pressure may make too much of a chemical that can cause inflammation of blood vessels. If you are taking blood pressure medication, the ACE-inhibitor family of drugs may also lower your CRP.
• If you are overweight, weight loss will reduce the risk of heart disease.
• So will regular aerobic exercise. No one knows yet if exercise lowers CRP or fights inflammation, but it may. We do know that physically fit people tend to have lower CRP.
• Smoking harms the entire cardiovascular system. No one should smoke.

To test or not to test

You may be wondering why the new study was hailed as a great advance since the experts are not telling you to go to your doctor and get tested. But a little farther down the road, CRP may be measured universally, just like blood pressure and blood cholesterol.

Meanwhile, people who already know they are at high risk for heart disease or are under treatment for it will probably not gain anything from having their CRP measured. But if you are at moderate risk (say, you are overweight and sedentary and don't follow a heart-healthy diet) and you have healthy cholesterol levels, the CRP test might be helpful. An elevated result may motivate you to become active and improve your diet-though you can do this without any test. Talk it over with your doctor.

(Copyright UC Berkeley Wellness Letter, www.berkeleywellness.com March 2003. Reprinted with permission by The Alexander Foundation for Women's Health.)