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 Yale-New Haven Hospital, New Haven, Connecticut, USA HealthLINK: Women's Health

March 3, 2000

News this month
Want to lower your risk? Try raising your levels of good cholesterol

For more than a decade, most clinical trials to prevent heart disease have focused on the impact of medications to lower low-density lipoproteins (LDLs), the so-called bad cholesterol. In an effort to lower their risk, millions of Americans have successfully reduced their LDL levels with the help of a group of drugs called statins.

Focusing attention on the "other" cholesterol
The importance of so-called good cholesterol, high-density lipoproteins (HDLs), and triglycerides in the blood has taken a back seat. Now dramatic results from a large clinical trial have renewed interest in the role of other lipids (fat-like substances) in the blood.

This is the first trial to demonstrate a reduced risk of cardiac events from intervention that raised HDL levels but did not reduce LDLs.

The study, published last summer, suggests people might benefit from increasing levels of HDLs. The Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial (VA-HIT), published in the New England Journal of Medicine in August, found that the generic medicine gemfibrozil slightly increased good cholesterol (7.5%) and significantly lowered triglycerides (24.5%), reducing the risk of a heart attack or death from heart disease by 22 percent and cutting the incidence of stroke by 29 percent. This is the first trial to demonstrate a reduced risk of cardiac events from intervention that raised HDL levels but did not reduce LDLs.

Good cholesterol fights plaque
Doctors often recommend cholesterol-lowering drugs for people whose LDL is above recommended levels. However, about one-quarter of the 12 to 13 million people in the U.S. with heart disease have normal amounts of LDL, while their HDL, the blood component that keeps arteries clean, is low. The two types of cholesterol have opposite effects on the progression of heart disease:

  • LDL tends to build up plaque in arteries
  • HDL tends to prevent or reverse buildups.

The VA study
"Gemfibrozil works. It’s cheap. It’s well-tolerated," said Dr. Hanna Rubins, chief of general internal medicine at the Minneapolis Veterans Medical Center and lead author of the study, which followed about 2,500 men at 20 veteran’s hospitals around the country.

In the study, 2,531 middle-aged men with a history of coronary artery disease were enrolled in the study between September 1991 and December 1993. Of these, 1,264 men were randomly assigned to take gemfibrozil while 1,267 others got placebos. At the start, average LDL levels were 111 mg/dL, close to ideal, while HDL was 31.5 mg/dL, well below what is considered the healthy level of 45 or higher. Gemfibrozil was chosen because it was felt to be most likely to raise HDL cholesterol and lower triglycerides without any marked effect on LDL cholesterol.

Study findings
The treatment raised HDL an average of 7.5 percent while LDL levels remained unchanged. After five years, 17 percent of patients taking gemfibrozil had died or suffered heart attacks compared with 21 percent in the control group.

Gemfibrozil therapy resulted in a significant reduction in the risk of major cardiovascular events in heart disease patients whose primary lipid abnormality is a low HDL cholesterol level. The findings suggest the rate of heart attack or death from heart disease is reduced by raising HDL cholesterol levels and lowering triglycerides, even if LDL levels remain unchanged.


Calculating cholesterol
Cholesterol guidelines can be confusing. Suppose you have total cholesterol of 280 mg/dL (high risk), but an HDL cholesterol reading of 70 (low risk). Are you at high risk or low risk for developing coronary artery disease? Many physicians calculate a risk ratio by dividing the total cholesterol by the total HDL. Despite a high, total cholesterol of 280 mg/dL, the patient is actually at lower than average risk with an HDL level of 70 mg/dL. The risk ratio is only 4 (280 divided by 70).

  • 3.5 or below is ideal
  • 4.5 is average risk
  • 5.1 or higher is potentially dangerous

The use of this ratio may predict coronary artery disease more accurately than total cholesterol levels.



Physician Referral Online

A free and confidential service
of Yale-New Haven Hospital.

Physician Referral Online
Using your own criteria, you can request information from a database of 900 area physicians who have registered to participate.

Request an appointment
We would be happy to assist you in scheduling an appointment with a member of the hospital's medical staff. Use the link above or call:

203-688-2000
or toll free
1-888-700-6543
to talk with a referral coordinator.
Brian Swirsky, M.D.

The right kind of cholesterol can be good for you

The VA-HIT trial is important for several reasons. Despite many studies that link high levels of bad cholesterol (LDL) to increased risk of coronary heart disease (CHD), it has never been clear whether raising the levels of good cholesterol (HDL) would also reduce risk. The VA-HIT is the first trial to demonstrate a significant reduction in risk from a medication that has no apparent effect on the bad cholesterol (LDL), but does raise good cholesterol (HDL).

"…low HDL levels [good cholesterol] are an even more significant predictor of heart attack and death from heart disease than high LDL levels [bad cholesterol]."

And the reduction in risk is dramatic. A 7.5 percent increase in good cholesterol (HDL) resulted in a 22 percent decrease in risk of heart attack or death from heart disease.

Good cholesterol more important than bad?
We believe low HDL levels are an even more significant predictor of heart attack and death from heart disease than high LDL levels. After looking at existing data comparing populations with heart disease with those without, we note a stronger correlation between low levels of good cholesterol and heart disease than between higher levels of bad cholesterol and disease.

"…for every percentage point we’re able to raise HDLs, we reduce risk by three percentage points."

From early studies, we also note a one-to-one relationship between lowering LDL levels and reducing risk, that is, if we lower LDL by 1 percent we also reduce risk by 1 percent. Raising good cholesterol results in a three to one risk ratio: for every percentage point we’re able to raise HDLs, we reduce risk by three percentage points. Clearly, raising good cholesterol is important.

Takes longer to benefit from increasing good cholesterol
The benefit, however, takes longer. In intervention trials using statin drugs to lower bad cholesterol, benefits were apparent as early as six months after treatment began. Raising good cholesterol levels resulted in benefits after two years in the VA-HIT study.

How does good cholesterol work?
HDL acts like a scavenger molecule, grabbing LDL from the walls of blood vessels and returning it to the liver. High HDL levels, above 45, appear to protect arteries from narrowing. According to some studies, levels below 35 are highly predictive of death from heart disease.

Why is the bad so bad?
LDL is the primary villain in the cholesterol story because when a person has too much LDL circulating in the blood, it can slowly build up within the walls of the arteries. Together with other substances it can then form plaque, a thick, hard deposit that can clog those arteries, or rupture and cause a blood clot.

Treating heart disease: the state of the art
Over the last decade there have been a series of important studies that have added to what we know about heart disease, but these have all focused either on lowering total cholesterol levels or lowering bad cholesterol. Lowering both of these has been demonstrated to lower the risk of heart attack and death from heart disease.

Where are we now? Researchers such as those in the VA-HIT study are now looking beyond total cholesterol and LDL to determine the role additional lipids play in heart disease such as good cholesterol or HDL, triglycerides and even more esoteric substances such as lipoprotein (a), Apolipoprotein A-1 and B as well as other substances such as homocysteine, an amino acid found in the blood. Our understanding of these blood components is in its infancy, but as we learn more, new medications will be developed to reduce risk more effectively than we can do now.

Many of the same behaviors that reduce your risk of heart disease also raise your level of good cholesterol:

  • aerobic exercise
  • healthy weight
  • stopping smoking
  • ERT
  • moderate alcohol consumption

What should you do?
When you look at lab results with your physician, look beyond total cholesterol numbers to determine your LDL and HDL levels. Information located on Yale-New Haven Hospital’s cardiac services site lists recommended LDL and HDL levels based on your total risk factor profile.

Lifestyle changes help
Many of the same behaviors that reduce your risk of heart disease also raise your good cholesterol levels, including aerobic exercise, maintaining a healthy weight, stopping smoking, estrogen replacement therapy for postmenopausal women and moderate alcohol consumption. If a healthy lifestyle doesn’t appreciably change your lipid profile, talk with your physician about what medication therapy might be appropriate for you.

Dr. Swirsky, FACC, is a cardiologist and a partner with The Cardiology Group practicing in New Haven and Branford. He is an attending physician at Yale-New Haven Hospital and an assistant clinical professor of medicine at the Yale School of Medicine.

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