The trouble with triglycerides

Good fats, bad fats, and in-between fats have one thing in common: they all contain triglycerides. These particles consist of three fatty acid chains linked by an alcohol called glycerol. When you eat a cheeseburger, your digestive system rips apart the triglycerides in the meat and cheese into their individual fatty acids. These are small enough to enter intestinal cells called enterocytes. Enterocytes stitch together fatty acids into new triglycerides, pack them with protein and cholesterol into huge particles called chylomicrons, and release them into the bloodstream. Chylomicrons ferry triglycerides to tissues, where they are burned for energy or stored. The liver also packages triglycerides into large particles called very-low-density lipoproteins (VLDLs).

As chylomicrons and VLDLs give up their fats to the body's cells, they shrink, becoming dense, cholesterol-rich particles. One of these is LDL, which readily burrows into artery walls. This is a key early step in the process that ends with cholesterol buildup in arteries.

Transformation into LDL isn't the only issue with high blood levels of triglycerides. The more abundant they are, the less HDL the body makes. That's a problem, because HDL scavenges LDL from the blood and from artery walls.

Measuring up

The amount of triglycerides in the bloodstream rises and falls throughout the day. After a fatty meal, triglycerides can be so abundant they give blood a milky tint. Within a few hours, they're mostly cleared out. Doctors traditionally test for triglycerides after an overnight fast so the results aren't thrown off by what you've just eaten. Categories are based on these fasting levels (see "Triglyceride levels").

Two reports in the Journal of the American Medical Association suggest that testing for triglycerides two to four hours after a meal offers a better gauge of their impact on heart disease.

One study followed almost 14,000 Danes for more than 25 years. Women with the highest nonfasting triglyceride levels at the start of the study were five times more likely to have died from a heart attack or other cardiac event than women with the lowest levels. For men, high triglycerides doubled the risk. The second study, conducted by Harvard researchers, followed 26,000 women for more than 10 years. Triglyceride levels measured two to four hours after eating — but not fasting triglyceride levels — were linked with heart attacks and other cardiovascular problems.

It's possible that people who don't clear triglycerides quickly are exposed to their dense, atherosclerosis-causing byproducts for longer than people who get rid of them quickly. It's also possible that triglycerides lingering in the bloodstream is a signal that muscle and other tissues are becoming resistant to insulin.

Triglyceride boosters

Fatty foods aren't the only cause of high blood levels of triglycerides. Other contributors include

• eating a lot of rapidly digested carbohydrates

• an underactive thyroid gland

• kidney disease

• diabetes

• overproduction of the hormones aldosterone or cortisol

• excess weight, especially extra pounds around the waist

• inactivity

• smoking

• medications such as high-dose thiazide diuretics or beta blockers, estrogen, tamoxifen, steroids, isotretinoin, and some anti-HIV drugs.

Inheritance also plays a role. Some people have high triglycerides due to genetic disorders, such as familial combined hyperlipidemia and familial hypertriglyceridemia.

What's the risk?

One reason triglycerides have long been shunted into the background is that their precise connection with heart disease has been iffy — some studies have shown a connection, others haven't. The latest meta-analysis, published in 2007 in Circulation, combined the results of 29 studies with more than 260,000 participants. In this report, people with high triglyceride levels were 70% more likely to have developed heart disease over an average of 10 years than those with normal levels. Some of this increase disappeared, though, when high LDL, low HDL, and other cardiac risk factors were taken into account.

That disappearance captures the big controversy over triglycerides: Are they harmful on their own, or are they stand-ins for other problems? It's a difficult question to answer, since high triglycerides are usually part of a pack of problems that also includes low HDL, high blood pressure, high blood sugar, and a large waist. These run together so often that, as a group, they are called the metabolic syndrome.

In other people, high triglycerides are a lone wolf. Even when they stand alone, however, they predispose individuals to heart disease.

Targeting triglycerides

When high triglycerides are accompanied by high LDL and low HDL — the usual scenario — they aren't the main focus of therapy. Guidelines recommend going after high LDL first, usually with a statin drug. Then it's time to work on triglycerides and HDL. Unless your triglycerides are extremely high, lifestyle changes are the best place to start. These can lead to impressive reductions in triglycerides.

Beware of bad fats. Cutting back on saturated fat (in red meat and full-fat dairy foods) and trans fat (in restaurant fried food and commercially prepared baked goods) can lower triglycerides.

Go for good carbs. Easily digested carbohydrates (white bread, white rice, cornflakes, and sugared soda) give triglycerides a definite boost. Eating whole grains and cutting back on sugared soda can help control triglycerides.

Check your alcohol. Moderate drinking is good for the heart. But in some people, alcohol dramatically boosts triglycerides. The only way to know if you are one of these "responders" is to avoid alcohol for a few weeks and have your triglycerides tested again.

Go fish. Omega-3 fats in salmon, tuna, sardines, and other fatty fish can lower triglycerides. Having fish twice a week is fine.

Aim for a healthy weight. If you are overweight, losing 5% to 10% of your weight can help drive down triglycerides. Losing more is even better.

Get moving. Exercise lowers triglycerides and boosts HDL.

Stop smoking. It isn't good for triglyceride levels or anything else.

What's in the medicine chest?

Although lifestyle changes are the first line of defense against high triglycerides, some people need more help. The four main medicines are statins, niacin, fibrates, and fish oil (see "Triglyceride-lowering drugs").

Because high triglycerides usually appear with high LDL, many doctors recommend combining a statin with one of the other three. Each drug has its own drawback or limitation. Some people can't tolerate niacin because it makes the skin flush; Niaspan, a once-a-day, extended-release, prescription version, can limit this problem. Taking a fibrate with a statin can increase the risk of muscle problems. Fish oil (2 to 4 grams a day) can increase the risk of bleeding, so it must be used with caution by anyone taking warfarin.

A number of ongoing clinical trials are looking at the impact of these combinations on triglycerides and heart disease.

Not to be ignored

The body needs some triglycerides in order to function properly. Too much of them can tip you toward heart disease or make it worse. Finding a balance can be tricky.

Some doctors turn a blind eye to triglycerides unless they are really, really high. That's not such a good idea. If your triglycerides are in the danger zone, above 200 mg/dL, try to bring them down by changing your diet, getting more exercise, and taking a triglyceride-lowering medication if needed. The payoff of these remedies is a healthier heart.