Which cholesterol test should you get?

(This article was first printed in the November, 2004 issue of the Harvard Health Letter. For more information or to order, please go to http://health.harvard.edu/health.)

The number of tests has proliferated. But for most people, the traditional fasting cholesterol is still the way to go.

Time to get your cholesterol checked. Okay, but which test should you get? It's not so simple anymore. Here is a rundown of some of the choices and their pros and cons:

Total cholesterol. This is the simplest and least expensive test. Total cholesterol doesn't vary much after you've eaten, so you don't have to worry about fasting. The test doesn't require any sophisticated lab work, either. The simple, do-it-yourself home cholesterol tests measure total cholesterol. A reading of 200* or below puts you in the desirable category; 200-239 is borderline high; and 240 or more is high.

But total cholesterol can be misleading. It includes both "good" high-density lipoprotein (HDL) cholesterol, and the "bad" varieties, chiefly low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL). So if your total cholesterol is in the desirable category, it's possible that you may have unhealthy levels of HDL (too low) and LDL and VLDL (too high). Think of total cholesterol as a first glimpse, a peek. Doctors are not supposed to make any treatment decisions based on this number alone.

Incidentally, although eating before the test doesn't affect total cholesterol or HDL levels to any great extent, levels can be lowered by stress (physical or psychological) or infection. An injury, stroke, or heart attack may have the same effect. Sometimes the first sign of cancer is a dramatically lower cholesterol reading. So if your cholesterol levels are unusually high or low, your doctor will probably want to repeat the test some weeks later. Abnormal readings may also lead to tests for other medical problems.

Total cholesterol and HDL. HDL wins its laurels as the "good" cholesterol because it sponges up cholesterol from blood vessel walls and ferries it to the liver for disposal. In contrast, LDL deposits the harmful fat in vessel walls.

HDL also contains less fat than LDL or VLDL. All these cholesterols are actually small bundles of protein and cholesterol. The cholesterol portion lowers the density of the package, so low density means more cholesterol and high density means more protein.

For the patient, there's really no difference between getting a total cholesterol and getting a total and an HDL cholesterol test together. Total and HDL can be measured using the same blood sample. Neither test requires fasting.

An HDL measurement is informative by itself and, in relation to total cholesterol, expressed as the total cholesterol-to-HDL ratio.

According to 2004 guidelines, an HDL level of 60 or above is protective against heart disease, and below 40 makes you vulnerable to it.

Plug your HDL into the total cholesterol-to-HDL ratio, and the smaller the number the better. For example, someone with a total cholesterol of 200 and an HDL of 60 would have a ratio of 3.3 (200 ÷ 60 = 3.3). If that person's HDL was low - let's say 35 -the total cholesterol-to-HDL ratio would be higher: 5.7.

Reports from the Framingham Heart Study suggest that for men, a total cholesterol-to-HDL ratio of 5 signifies that they're at average risk for heart disease; 3.4, about half the average; and 9.6, about double the average. Women tend to have higher HDL levels, so for them, a ratio of 4.4 signifies average risk; 3.3 is about half the average; and 7, about double.

Many people with a high HDL also have a low total cholesterol-to-HDL ratio, so computing it may not add that much useful information. But some clinicians like to use it as an indicator of heart disease risk. And if you have a high level of total cholesterol, it may be less alarming if your total-to-HDL ratio is low.

LDL cholesterol. The LDL measurement is usually considered the most important for assessing risk and deciding on treatment. The definition of a healthy level keeps on getting lower. Current guidelines say an LDL of 100 is "optimal." In a revision of the guidelines in early 2004, doctors were advised that an LDL of less than 70 should be a "therapeutic option" for very-high-risk patients. Some experts say that would be a healthy LDL goal for all of us.

The fasting cholesterol test is the traditional way to measure the level of LDL, but it doesn't measure LDL directly. Instead, your LDL is computed by plugging the measurements for total cholesterol, HDL, and triglycerides into a formula called the Friedewald equation (named for William Friedewald, who developed it). This is the equation: LDL = Total cholesterol - HDL - (Triglycerides ÷ 5)

Although triglyceride levels can be significant by themselves, the triglycerides ÷ 5 quotient is included in the equation as a way to indirectly calculate the VLDL level. So, in essence, the Friedewald equation subtracts your HDL and an estimate of VLDL from your total cholesterol to get your LDL level.

You have to fast for about 12 hours before the test because triglyceride levels can shoot up 20%-30% after a meal, which would throw off the equation. Alcohol also causes a triglyceride surge, so you shouldn't drink alcohol for 24 hours before a fasting cholesterol test.

Another important limitation: At a triglyceride level of about 250 or higher, the Friedewald equation becomes less reliable because dividing triglycerides by a factor of 5 provides a less accurate estimate of VLDL.

Direct measurement of LDL. Several companies are marketing tests that measure LDL directly rather than estimating it from an equation. Direct LDL testing has become popular in Florida and some other southeastern states. They have two advantages. First and foremost, you don't have to fast. Second, the measurements are accurate even if your triglycerides are high.

The chief drawback of the direct LDL tests is their cost. If the testing company does several other tests in addition to LDL, the bill can climb into the hundreds of dollars, and it may not be covered by your insurance. The new wave of tests may also give us more information than we can really use. In fact, some experts see direct LDL testing as a Trojan horse for more and more blood tests that have little practical value. For example, HDL can be broken down into HDL2 and HDL3. Some studies suggest that HDL2 is more potent and desirable. But, at this point, there is no reason to know your HDL2 level.

Other calculations and tests. If your triglycerides are between 200 and 500, your doctor may want to know your non-HDL level and use that measurement to guide your treatment. It's calculated simply enough:

Total cholesterol - HDL = non-HDL

Put another way, non-HDL cholesterol is the sum of VLDL and LDL levels.

Non-HDL becomes a good predictor of heart disease in people with high triglycerides because as triglycerides increase, so do VLDL levels, and VLDL (not just LDL) starts to play a larger role in atherosclerosis.

Apolipoprotein B, usually shortened to apo B, is a signature component of LDL, VLDL, and other blood lipids that cause atherosclerosis. Research has shown that there's a strong relationship between apo B levels and heart disease. Some experts argue that the relatively simple test for apo B could replace the increasingly complicated measurement of cholesterol subtypes. The rebuttal: Both doctors and patients have a lot of experience with cholesterol testing that shouldn't be abandoned for an unfamiliar test.

C-reactive protein (CRP) is a protein in the blood that increases with inflammation. Because atherosclerosis is fundamentally an inflammatory process, many experts believe that CRP testing could lead to early detection and therefore save lives. But there's also concern that the CRP test is just piling on more information and tests. For many, body weight, family history, and HDL and LDL cholesterol levels are just fine for assessing heart disease risk and determining steps that should be taken to reduce it. The American Heart Association says CRP tests are warranted for people at intermediate risk for heart disease, but not those at the low and high ends of the risk spectrum.

What should you do?

The current guidelines recommend a fasting cholesterol test every five years for everyone beginning at age 20. That's sound advice. A fasting cholesterol test gives you the important numbers: total, LDL, and HDL cholesterol, as well as triglyceride levels. If you have difficulty fasting or your triglycerides are over 250, you are a candidate for one of the new tests that measure LDL directly. But unless you're a special case, sophisticated breakdowns of the various cholesterol types will only give you a case of information overload. Skip them and stick to the basics.

(This article was first printed in the November, 2004 issue of the Harvard Health Letter. For more information or to order, please go to http://health.harvard.edu/health.)

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