Cholesterol Tests

About twenty years ago, people started to realize that measuring total cholesterol wasn’t enough—you need to know your HDL and LDL breakdowns in order to best assess your risk. Along came the fasting full-lipid test. Now, some people are arguing that that isn’t enough either.

They say that measuring your LDL and HDL subfractions, along with other lipoproteins, gives you the best idea of which treatments are right for you. (Subfractions are basically just further breakdowns of the category of LDL or HDL, similar to how you could break down the category of low-fat milk into skim, 1 percent, and 2 percent.)

A few companies offer these tests—namely Atherotec, Berkeley Heart Labs, and Liposcience. Though each uses a different method to get to the result, all of them generally measure the same things:

  • Direct LDL Measurement. In the basic lipid profile, LDL cholesterol is calculated by using a mathematical formula based on the measurements of triglyceride, total cholesterol, and HDL cholesterol levels. While this method has been widely used as the gold standard for determining LDL cholesterol levels for about forty years, it can be inaccurate under certain conditions.

The higher the triglyceride level (especially above 250 mg/dL), the greater the potential error in calculation of the LDL value. According to some, this calculation can be off as much as 25 percent. And the worst part is that it underestimates the LDL level, making people think they have a healthier cholesterol level than they really do.

Newer tests measure the LDL cholesterol level directly, and they do not require that the blood sample come from a patient who has fasted for twelve hours. Although the accuracy and reproducibility of these tests have been more variable, they have been improved over the past few years and are widely used.

  • Measures for Different Types of LDL. Using these advanced tests, LDL gets broken down into two categories—one of which is smaller and denser than the other. Higher levels of the small, dense LDL are associated with higher rates of heart disease, partly because these smaller LDL can penetrate more easily into the lining of the arteries.

A few large studies have found that high levels of small, dense LDL triple a person’s risk for heart disease. Small, dense LDL particles also can’t be reabsorbed by the liver as easily, which gives them more time to do their damage.

  • Measures for Different Types of HDL. Similarly, HDL can be subclassified into denser and less dense particles. In this case, the different HDL particles are known as HDL 2 (less dense) and HDL 3 (more dense). Routine laboratory tests do not differentiate these two HDL particles—they just lump them together—but these more advanced tests do.

It is good to have high levels of both HDL 2 and HDL 3, but most studies indicate that high HDL 2 levels may be more potent in lowering your risk of heart disease than high HDL 3 levels.

In a study of 1,799 Finnish men, for example, the risk of a heart attack was four times greater in men with low HDL 2 levels, three times greater in men with low HDL levels (not distinguishing HDL 2 from HDL 3), and only two times greater in men with low HDL 3 levels.

Thus, it was low HDL 2 levels that carried the greatest risk. Stated another way, someone with particularly high HDL 2 levels would have the greatest protection.

  • Measures for Remnant Lipoproteins. Remnant lipoproteins (also called intermediate-density lipoproteins) are the particles that are trapped in between the conversion of triglyceride-rich VLDL to cholesterol-rich LDL. These particles are relatively rich in both triglyceride and cholesterol and can penetrate into the artery wall to stimulate atherosclerosis in much the same way that LDL particles do.
  • Measures for Lp(a). Lp(a) is an emerging risk factor for heart disease, and these new tests can measure for Lp(a) at the same time as measuring your other lipoprotein levels.

Knowing your specific lipid profile may allow you and your doctor to tailor your treatment accordingly. For example, if you have high small, dense LDL levels, your doctor may ask you to reduce your sugar intake, and if you have high triglyceride levels, you may need to reduce the sugar and alcohol in your diet.

Your drug treatment may change depending on these tests as well. A statin or niacin may help with high remnant lipoproteins, for example, while niacin is the drug of choice for elevated Lp(a) levels.

However, for the most part, the specialized tests have not been convincingly demonstrated to improve upon the standard lipid profile in the prediction of coronary disease risk in the vast majority of patients. National guideline panels have not yet accepted these tests as better predictors of heart disease risk.

This is an area where advances in medical science could lead to changes in the testing we do in the next few years. As they are substantially more costly than the standard lipid profile, I think that most patients should stick with the standard lipid tests for now. These are exceptions to this general rule:

  1. People who have coronary disease but normal cholesterol levels as shown through a standard fasting test.
  2. People whose family members have a strikingly high rate of coronary disease despite a healthy lifestyle and a clean bill of health as reported by a fasting test