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Harvard Heart Letter | February 2008
Clarification
In the February 2008 issue, the
sidebar on very high triglycerides failed to mention a key dietary
change for controlling them: cutting back on easily digested
carbohydrates. Eating less white bread, chips, pastries, sugared sodas,
and other sources of processed carbohydrates and replacing them with
healthful protein such as fish and poultry, unsaturated fats, and
minimally processed foods such as whole grains, vegetables, beans, and
nuts can have a substantial effect on triglycerides.
Triglycerides: A big fat problem
This forgotten fat is a source of confusion — and heart disease.
Why
is it that the most common form of fat in food and in the bloodstream
is the one that’s most often ignored? Triglycerides take a back seat to
low-density lipoprotein (LDL) and high-density lipoprotein (HDL)
largely because their precise role in heart disease has been something
of a mystery.
That’s changing. Researchers are getting a
grip on how triglycerides add to atherosclerosis, the artery-clogging
process at the root of most heart disease. This knowledge may change
how triglycerides are measured and when they need to be treated.
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.
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Triglyceride levels
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Classification
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Triglyceride level*
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Normal
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Less than 150
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Borderline high
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150–199
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High
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200–499
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Very high
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500 or higher
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*Values in milligrams per deciliter (mg/dL)
Source: National Cholesterol Education Program
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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
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eating a lot of rapidly digested carbohydrates
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an underactive thyroid gland
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kidney disease
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diabetes
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overproduction of the hormones aldosterone or cortisol
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excess weight, especially extra pounds around the waist
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inactivity
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smoking
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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.
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Very high triglycerides
When
fasting triglycerides shoot above 500 mg/dL, more than the heart and
arteries may be at risk. Pancreatitis is often seen with triglyceride
levels above 1,000 mg/dL. Near 2,000 mg/dL they can trigger a harmful
buildup of fat in the liver and retina. They can also spark the
eruption of itchy, pimple-like xanthomas (zan-THOE-muhs) on the hands,
feet, arms, legs, and buttocks.
If you are
diagnosed with very high triglycerides, a search for causes related to
genes, disease, or medication is in order. Controlling such high levels
usually includes a very low-fat diet (under 15% of calories from fat),
no alcohol, and triglyceride-lowering drugs.
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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.
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Triglyceride-lowering drugs
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Drug family
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Effect on triglycerides
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Other effects
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Most common side effect
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statins (Crestor, Lescol, Lipitor, Mevacor, Pravachol, Zocor, generic)
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decrease 10%–50%*
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decrease LDL
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Muscle pain
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niacin (Niaspan, over-the-counter products)
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decrease 20%–35%
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decrease LDL, increase HDL
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Flushing
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fibrates (Lopid, Tricor, generic)
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decrease 25%–50%
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increase or decrease LDL, increase HDL
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Upset stomach
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fish oil (Lovaza, over-the-counter products)
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decrease 20%–50%
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decrease LDL, increase HDL
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Fishy taste/burps
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*depending on the statin and dose
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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.
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