Up with HDL, the ‘good’ cholesterol

Guidelines mainly target LDL cholesterol, but HDL matters too.
Up with HDL, the ‘good’ cholesterol
By Partners Harvard Medical International
Tue 08 Jul 2008 04:00 AM

Guidelines mainly target LDL cholesterol, but HDL matters too.

Among the many things we can do to reduce our risk for cardiovascular disease, the leading cause of death in women in the United States, is to pay attention to cholesterol levels.

Although for most people it's not as potent a risk factor as smoking or high blood pressure, excess cholesterol in the blood may set the stage for atherosclerosis, which can lead to heart attack and stroke.

Cholesterol, a substance needed by cells throughout the body, travels through the bloodstream in protein packages called lipoproteins. The lipoprotein of greatest concern to clinicians is low-density lipoprotein (LDL), the so-called bad cholesterol. If more LDL is produced than the cells can absorb, it lodges in artery walls and contributes to the buildup of atherosclerotic plaque.

Excess cholesterol in the blood may set the stage for atherosclerosis.

In recent years, thanks largely to the availability of the powerful cholesterol-lowering drugs called statins, driving down LDL has been the main target for improving cholesterol levels. In studies involving mostly men (with a fair representation of women), statins have been shown to cut the risk of developing and dying from heart disease by 30% to 40%.

But there's more to the story of cholesterol and cardiovascular risk than LDL. Another key player is high-density lipoprotein (HDL), dubbed the "good" cholesterol. HDL removes LDL from the artery walls and ferries it back to the liver for processing or removal. HDL also acts as an antioxidant, an anti-inflammatory, and an antithrombotic (reducing clot formation in the coronary arteries).

Both women and men with low levels of HDL are more likely to have heart attacks and strokes; high levels appear to be protective. In the Framingham Heart Study, low levels of HDL were an even more potent risk factor for heart disease than high levels of LDL.

And the effect of raising HDL was stronger in women than in men: a 1-milligram-per-deciliter (mg/dL) increase in HDL cholesterol was associated with a 3% lower rate of heart disease in women, compared to 2% in men.

IN 2007, researchers reported that low HDL levels predicted higher cardiovascular risk even among patients (women and men) who were being treated with statins and had optimal LDL levels - that is, below 70 mg/dL (New England Journal of Medicine, Sept. 27, 2007). Other studies have linked high HDL levels to a reduced risk of stroke, greater longevity, and better cognitive function in old age.

How HDL helps

Cholesterol travels in the blood attached to lipoproteins. Low-density lipoprotein (LDL) enters the walls of arteries, where it contributes to the buildup of atherosclerotic plaque. High-density lipoprotein (HDL) removes LDL from the artery walls and carries it back to the liver. HDL also helps quell inflammation and protect the cells lining the arteries' inner surface (endothelium).

Taking aim at HDL

According to a review of research on HDL as a therapeutic target (Journal of the American Medical Association, Aug. 15, 2007), there's some evidence, though no solid proof, that the risk of cardiovascular events in humans can be reduced by HDL-raising alone - that is, without also lowering levels of LDL or triglycerides (fatlike substances in the blood that are another significant risk factor for heart disease, particularly in women).

Many believe that agents designed specifically to boost HDL are the next frontier in cholesterol-targeted drug therapy, especially since LDL-lowering statins don't help everyone. The field got off to a rocky start in December 2006, when phase III trials of one such agent, torcetrapib, were halted because the drug appeared to increase the risk of cardiovascular events and death.

The B vitamin niacin raises HDL and lowers LDL and triglyceride levels. Drugs called fibrates also raise HDLs and lower triglycerides. But the use of niacin and fibrates has been limited by side effects, which include flushing, itching, and gastrointestinal upset.

Statins, whose primary function is to lower LDL levels, also increase HDL levels - by a modest 5% to 10%. In some studies, increases in that range have led to reductions in coronary disease and death, particularly in people who had low HDL to begin with. What to do

More research is needed to understand exactly how HDL works, but a growing body of evidence suggests it's an important and partly controllable risk factor for cardiovascular disease. There's no "normal" level of HDL - but cholesterol experts suggest we should aim for more than 60 mg/dL. In women, HDL levels below 50 mg/dL increase the risk of heart disease.

Some women are lucky enough to inherit genes that direct a high production of HDL, while others are dealt a less favorable hand. But genes are only part of the story.

There are several things we can do to nudge up our HDL levels, and most of these strategies also help reduce our risk for many other chronic conditions, including diabetes and certain cancers. So let HDL-boosting be one more reason to stay on track with some healthy lifestyle choices that should be pretty familiar to most of us by now. Specifically:

Aerobic exercise. Moderate-to-vigorous aerobic exercise can boost HDL by 5% to 10%. Aim for five 30-minute sessions per week. Brisk walking, jogging, and cycling are all good choices.

The idea is to keep your heart rate up for at least 20 minutes - at a level of 50% to 85% of your maximum heart rate, which is about 220 beats per minute minus your age. For example, a 60-year-old woman, whose maximum heart rate is 160 beats per minute (220 minus 60), should strive for a target heart rate of 50% to 85% of 160 - that is, 80 to 136 beats per minute.

Weight loss. If you're overweight or obese, you can boost your HDL level by about 1 mg/dL for every seven pounds lost, although any amount of weight loss will help. Aim to bring your body mass index (BMI) into the normal range (less than 25), at a rate of about 4.5 pounds lost per month.

A word of caution: ‘yo-yo' dieting - repeatedly losing and regaining weight - can lower HDL. In the Framingham Heart Study, weight cyclers (both women and men) were at increased risk of heart disease and death.

Smoking cessation. Smoking lowers HDL cholesterol. Levels rise by as much as 15% to 20% after you quit.

Healthy fats and carbohydrates. Avoid trans fats, which increase bad cholesterol and decrease good cholesterol. Replace saturated fat and trans fats with poly- and monounsaturated fats from plant oils (olive, canola, soy, flaxseed), nuts (almonds, peanuts, walnuts, pecans), and fatty fish (salmon, tuna, mackerel).

The OmniHeart trial showed that a diet that derives 37% of its calories from unsaturated (mostly monounsaturated) fat serves to lower LDL cholesterol and triglyceride levels while raising HDL levels. Avoid highly refined carbohydrates, such as white-flour products; instead, choose whole-grain products.

Alcohol consumption. One drink per day (five ounces of wine, 1.5 ounces of liquor, or 12 ounces of beer) can boost HDL by about 4 mg/dL.

Medications. If low HDL is a serious problem, you may need medications in addition to lifestyle therapy. Niacin, available over the counter, is the most effective HDL-raising medication currently available. It improves cholesterol levels across the board, increasing HDL by 15% to 35% while reducing triglycerides by 20% to 50% and LDL levels by 10% to 20%.

The most common side effects, flushing and itching, are less likely if you take it after a meal, or an hour after taking an aspirin. So-called flush-free niacin products are available, but they have no effect on cholesterol levels. Look for a USP-approved niacin, or better yet, ask your clinician about prescription intermediate-release niacin (Niaspan).

Niacin can be strong medicine, particularly at the doses needed to change cholesterol levels (500 to 1,000 milligrams or more per day), so it's important to work with your clinician if you want to try it.

This article is provided courtesy of Partners Harvard Medical International. © 2008 President and Fellows of Harvard College

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