Letter to The Wall Street Journal sent by Paul Rosch commenting an article by Amy Dockser Marcus . The letter was not published. Marcus' article is included below.
Aug 22, 2003
To The Editor
indicated, "Why Low Cholesterol May Not Protect You" (August 19),
there is a push to prescribe statins for people with normal cholesterol and
LDL values, including all diabetics and hypertension. But how will dosage and duration of treatment be determined?
There is abundant evidence that the cardioprotective effects of
statins are related to their anti-inflammatory activities rather than any
effects on lipids. Therefore,
the current goal of lowering LDL to an arbitrary that the vast majority of
patients are unable to achieve is not only inappropriate but dangerous.
Contrary to pharmaceutical company propaganda, statins are not as
safe as generally believed and since adverse side effects are related to
dosage and duration of therapy, their incidence will surely increase if
current guidelines are followed. Like
aspirin, the anti-inflammatory effects of statins may be attained at dosages
much lower than for other indications.
Measuring markers of inflammation such as CRP might be a much safer
way to monitor statin therapy.
J. Rosch, M.D., F.A.C.P.
August 19, 2003
Low Cholesterol May Not Protect You
"My primary-care doctor couldn't believe it," says Mrs. O'Malley, 68, a retired schoolteacher in Edmonds, Wash. "She said there was nothing to make her suspect that I had a heart condition."
For years, doctors and public-health messages have focused on the importance of maintaining low cholesterol to prevent heart attacks. But now, more cardiologists believe this emphasis overlooks a growing number of other risk factors, leaving huge numbers of people unaware that they are vulnerable. Some cardiologists estimate that as many as 25 million to 30 million people in the U.S. have cholesterol levels that are considered normal or even low -- but are nonetheless at such high risk for heart disease that they need to immediately change their lifestyles or even seek medical treatment.
Doctors are identifying a
host of new risk factors, including inflammation and calcium deposits in the
arteries, and they are paying more attention to better-known factors such as
high blood pressure, obesity and diabetes. Earlier this year, the American
Heart Association and the Centers for Disease Control and Prevention issued
a statement to physicians that for the first time emphasized the role of
coronary-artery inflammation in causing heart disease.
The National Heart, Lung and Blood Institute, whose National Cholesterol
Education Project issues recommendations on cholesterol levels, is
developing guides for physicians and patients that address obesity and other
A number of studies are focusing on new approaches. A 15,000-patient clinical trial called Jupiter is preparing to examine whether people with normal cholesterol but high levels of coronary-artery inflammation can lower their heart-attack risk by taking AstraZeneca PLC's Crestor. Several companies, including Pfizer Inc. and Esperion Therapeutics Inc., are running trials of drugs that try to raise people's levels of high-density lipoprotein, or HDL -- a so-called good cholesterol that appears to get rid of harmful plaque in the arteries.
Meanwhile, cardiologists are taking other risks more seriously. While obesity is known as a factor in heart disease, more doctors are looking at excess body fat around the abdomen. Others are looking at diabetes and high levels of fats in the blood, and some studies have identified tooth loss caused by gum disease as an indication that a person may be at higher risk for heart disease.
Yet even as doctors look beyond cholesterol, there is a growing consensus that today's recommended cholesterol levels aren't low enough. The current target for low-density lipoprotein, or LDL, the "bad" cholesterol that can cause plaques to build up inside the arteries, is below 130 milligrams per deciliter for most people and below 100 mg/dL for people with other heart-disease risk factors. But three clinical trials are testing the notion that "even lower is better," says Richard Pasternak, the spokesman for the American Heart Association. These studies may suggest that the optimal level of LDL cholesterol should be less than 80 mg/dL.
All this is leading more doctors to argue that far more people should be taking medications to reduce the risk of heart attacks. Drugs called statins, which include Pfizer's Lipitor and Merck & Co.'s Zocor, have proved successful in lowering cholesterol in the body, helping to drive a $20 billion world-wide market.
"This is the most important public-health question to come out of the field in a decade," says Paul Ridker, director of the Center for Cardiovascular Disease Prevention at Brigham and Women's Hospital in Boston. "Many of us are starting to ask: Should more people be on these drugs?"
William Witzel says he wants to know the answer. A 59-year-old
businessman living outside Aurora, Ill., Mr. Witzel never suspected he might
have a heart problem. He's fit, eats right, exercises daily, and doesn't
smoke; his cholesterol level is low. But in 2001, he was rushed to the
emergency room with chest pains. Doctors could find nothing wrong and
released him, but a subsequent visit to a cardiologist revealed that he had
a blocked coronary artery. He has had two more episodes of chest pains since
then and now has three cardiac stents.
Although Mr. Witzel's cholesterol level is good, he has a high level of C-reactive protein, a marker for inflammation, in his blood. His cardiologist is treating him with drugs, but Mr. Witzel and his wife say it came as a surprise to them that he faced such a risk for a heart attack. "My doctor assumed I was safe because of my great cholesterol levels," says Mr. Witzel.
Mr. Witzel's experience is increasingly common, cardiologists say. But the idea of prescribing more statins bothers some doctors, who worry that patients may think taking drugs protects them from having to change their lifestyle. "You can eat your way through a statin," says Dr. Pasternak, who is also a cardiologist at Massachusetts General Hospital in Boston. Patients have some alternatives, including having a diet low in saturated fats and cholesterol and increasing their physical activity, though for many people, lifestyle changes alone won't lower heart-attack risks enough to make medication unnecessary.
Others caution that putting more patients on the drugs will come with a cost. "Monitoring people on drugs is expensive," says Peter Libby, chief of the cardiovascular division at Brigham and Women's Hospital in Boston. "And although many of these drugs are very safe, the more people who are exposed to them, the more potential adverse side effects there will be, even if they are rare." The most common side effects of statins are fatigue, upset stomach and cramps.
There are now some relatively inexpensive tests that can help doctors flag more people who may have heart-disease risks. A C-reactive protein test costs around $20. Some people are also paying out-of-pocket for a $400-$500 plaque imaging test that, using a computerized X-ray, measures the amount of calcified plaque in the arteries.
Also, the growing research in the field offers some tantalizing suggestions on additional things people can do to help protect themselves against heart attacks. None of them have yet been endorsed by national groups, and cardiologists caution that there is a need for more trial data, but the results have provided further impetus to get doctors moving beyond cholesterol. A study of over 140,000 elderly patients released this year indicated that getting a vaccination against influenza lowered the risk of hospitalization for heart disease.
A study published in June indicated that in mice the pneumococcal vaccination against pneumonia decreased the extent of heart disease. And some companies are working to develop vaccines that would help protect against heart disease. Avant Immunotherapeutics Inc. is testing a vaccine in humans that would get the body to produce more of the protective HDL cholesterol; results from a trial will be published this fall. Researchers at Cedars-Sinai Medical Center in Los Angeles and in Sweden are testing a vaccine in animals that they hope will immunize the body against LDL cholesterol buildup.
Dr. Pasternak, the Heart Association spokesman, says that since many of these remedies are still being studied, the best suggestion is "to start with things that don't come in the form of a pill."
Mrs. O'Malley is doing both. After recovering from surgery, she joined a trial at the University of Washington School of Medicine that put her on simvastatin, to reduce her LDL level, and niacin, to boost her HDL level. The medicines worked and she hasn't had any more cardiac issues. But she has increased the amount of exercise she does, doing a vigorous cardiovascular workout for 2½ hours three times a week. She says she is glad she did. Two of her brothers have subsequently died of heart attacks.
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