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Cholesterol: An Ever-Changing Story

By Antonio M. Gotto Jr., MD, DPhil for WebMD Health

In the past few years, our understanding of cholesterol and the role it plays in heart disease has improved dramatically. We now know that lifestyle changes and drug therapy, when appropriate, can significantly reduce the risks for heart attacks for many people. In individuals with a history of heart disease, treatment also can help prevent strokes and death. In 2001, an expert panel released the latest U.S. guidelines for managing cholesterol, and during the summer of 2004, those guidelines were updated to reflect the latest science. What's new in these guidelines that may be important to your heart health?

Even Moderately High Cholesterol Can Be Risky

First, doctors have a growing appreciation that high cholesterol works in tandem with other risk factors to increase your risk for heart attack. We now have the ability to estimate your risk for having a heart attack, using a calculation that includes cholesterol, age, blood pressure, and smoking status. For instance, if you've never had a heart attack and your calculated risk for having one in the next 10 years is 20% or greater, the new guidelines recommend you be treated as if you have already had a heart attack. Your doctor may begin cholesterol-lowering treatment, even if your cholesterol levels alone don't seem alarming, because your risk is high.

Second, we've defined a cluster of risk factors called the metabolic syndrome. These risk factors may appear to be mild when considered individually, but when added together, they can raise the risk for heart disease significantly. Also called syndrome X or insulin resistance syndrome, this condition is present when people have three of the following five characteristics:

1. A waist measurement of more than 40 inches for men or more than 35 inches for women
2. Blood pressure of 130/80 or higher
3. High-density lipoprotein (HDL), the "good" cholesterol, less than 40 for men or less than 50 for women
4. Triglycerides, another type of blood fat, of 150 or greater
5. Blood sugar level of 110 or greater

The metabolic syndrome affects at least 47 million adults in the U.S. and can also increase your risk for developing diabetes, another important risk factor for early heart disease.

What other changes are in the new guidelines compared with previous guidelines?

1. If you have diabetes, your risk is so high that guidelines recommend you get as aggressive cholesterol treatment as if you had had a heart attack.
2. Previously, a "good" cholesterol level of 35 or lower was too low. Now an HDL level less than 40 is too low. An HDL of 60 or higher is ideal.

As a result of these changes, the number of people in the U.S. who may benefit from cholesterol-lowering drugs has skyrocketed from 12 million to 36 million people.

Know Your Numbers

Knowing your cholesterol numbers is important. Your total cholesterol level should be no higher than 200. Your "good" cholesterol should be no lower than 40.

"Bad" low-density lipoprotein (LDL) cholesterol should be 100-130 or lower, depending on your overall risk for heart disease. Depending on that risk, drug therapy may be optional for people with LDL levels between 100 and 130. An LDL below 100 is optimal. Yet a study from the United Kingdom showed great benefits when people in that borderline range were treated with a statin.

There are several treatment options. A healthy diet and exercise program can reduce cholesterol levels for some people. For those who need more help, medication can target a specific problem.

1. Drugs caned statins effectively lower LDL and have proven clinical benefits in several trials
2. Drugs called fibrates can increase HDL and lower triglycerides, and they have clinical benefits
3. Niacin can increase HDL and lower LDL and triglycerides.
4. New drugs, known as cholesterol absorption inhibitors, may work well in combination with statins to control cholesterol.

For Those at Greater Risk, More Intensive Treatment Options

If you're at moderately high to very high risk for a heart attack, the updated cholesterol guidelines released in the summer of 2004 contain some new treatment recommendations for you and your doctor to consider. They're based on five new studies published since the release of the 2001 guidelines, which indicate that for people at elevated risk, lowering LDL levels below previous thresholds helps in preventing heart attacks.

1. Very High Risk: You're at very high risk for a heart attack if you have existing cardiovascular disease together with multiple other risk factors, especially diabetes or metabolic syndrome. For you, the updated guidelines give your doctor the option of drug therapy to reduce your LDL cholesterol level to below 70.
2. High Risk: You're at high risk for a heart attack if you have coronary heart disease or disease of the blood vessels to the brain, or diabetes, or multiple risk factors-like smoking and hypertension-that give you a greater than 20% chance of having a heart attack in the next 10 years. The new guidelines recommend drug therapy to lower your cholesterol if your LDL is between 100 and 129 (the old guidelines recommended this approach when LDL was 130 or higher), and make drug therapy an option if your risk continues to be high despite having LDL levels of 100 or lower.
3. Moderately High Risk: You're at moderately high risk for a heart attack if you have multiple risk factors that give you a 10-20% chance of having a heart attack within 10 years. For you, the new guidelines haven't changed your LDL cholesterol goal-you should still strive for LDL under 130. But your doctor now also has the therapeutic option of setting a lower goal-under 100-and to use drugs like statins to reach this goal.

Ongoing studies continue to test the bottom threshold of LDL cholesterol to determine just how low we should go, both for people at elevated risk for a heart attack and for people with no significant risk factors.

New research is examining whether inflammation plays a role in the development of heart disease. We're also learning more about the role of a substance called C-reactive protein (CRP), a marker in the blood for such inflammation, in heart attack risk. Studies published in 2004 provide suggestive evidence that lowering CRP levels may be associated with a decreased risk for heart attack, even when LDL cholesterol levels are normal. More research is needed, however. Scientists are also investigating genetic approaches that may directly attack heart disease and cholesterol disorders. Another potential new approach involves a vaccine designed to coax the body into making more protective HDL while lowering LDL. While the cholesterol story evolves, the major point remains the same: high cholesterol is a key risk factor for heart disease that must be treated, without a doubt.

Antonio M. Gotto Jr., MD, DPhil, is the dean of Weill Medical College of Cornell University in New York City and a professor in the department of medicine.

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