Second Thoughts About “Good” Cholesterol Effects
You’ve heard over and over—including in the pages of this newsletter—about “good” HDL cholesterol, as opposed to “bad” LDL cholesterol. People with higher levels of HDL have lower rates of heart disease. Those with low HDL are often advised to try to boost it with diet, exercise or even by taking niacin. It’s thought that HDL works by carrying away artery-clogging cholesterol.
But a startling new study using modern genetic testing has challenged the theory of a cause-and-effect relationship between high HDL and lower heart disease. Higher levels of HDL, the findings suggest, may simply be a marker for something else that makes heart disease less likely, rather than protective on its own.
Sekar Kathiresan, MD, of Massachusetts General Hospital,
and colleagues sought to isolate the effects of “good” and “bad” cholesterol by studying people with genetic variations that predispose them to higher or lower HDL or LDL. As expected, people with naturally high LDL were more likely to have heart disease, and those lucky enough to have genes for lower LDL had lower risk.
The story was different for HDL, however. First, researchers
studied 116,000 people, looking for a single HDL-raising genetic variant seen in about 2.6% of the population. “We found absolutely no association between the HDL-boosting variant and risk for heart disease,” says Dr. Kathiresan. “That was very surprising to us.”
Next the scientists looked for heart benefits from a group of 14 genetic variants that also affect HDL levels, using data on 53,000 people. Again, they found no association between genetically higher HDL and lower heart disease.
Rather than protecting against heart disease, Dr. Kathiresan
suggests, HDL may simply be associated with other factors that do affect risk. That fits with the results of recent clinical trials of four drugs (torcetrapib, fenofibrate, niacin and dalcetrapib), which all increased HDL cholesterol but failed to reduce heart disease risk.
Alice H. Lichtenstein, DSc, director of Tufts’ HNRCA Cardiovascular Nutrition Laboratory, comments, “HDL that circulates in plasma is made up of a variety of different types of particles. The relative amounts of each of the different types or sub-populations of particles may be a better predictor of heart disease risk than just total HDL cholesterol levels. These new findings mean we need to learn a little more about what genes, niacin and lifestyle modifications modify which types of HDL particles. The jury is still out on this topic.”
TO LEARN MORE: The Lancet, online first, dx.doi.org/10.1016/S0140-6736(12)60312-2.