There May be No Such Thing as "Good" Cholesterol

The control of cardiovascular disease has been an important reason for the continued rise in life expectancy, especially in the richer countries. One of the most important risk factors for a heart attack (myocardial infarction) is high cholesterol. When we use that term generically we mean high levels of LDL (low-density lipoprotein), which causes clotting of the arteries that can then lead to a potentially fatal heart attack. LDL can be lowered by changes in diet (and exercise), often combined with drugs called statins. LDL is the "bad" cholesterol, whereas HDL (high-density lipoprotein) cholesterol has long been considered to be a "good" cholesterol, because people with high HDL are known to have a lower probability of a heart attack. As a consequence, a lot of effort (albeit largely unsuccessful) has gone into figuring out ways to raise HDL. However, a new study just published in The Lancet and reported in the New York Times suggests that the relationship between HDL and heart attack may not be causal. If this is true, then trying to raise your HDL is unlikely to save your life.

The study’s authors emphasize that they are not questioning the well-documented finding that higher HDL levels are associated with lower heart disease risk. But the relationship may not be causative. Many assumed it was because the association was so strong and consistent. Researchers also had a hypothesis to explain how HDL might work. From studies with mice and with cells grown in the laboratory, they proposed that HDL ferried cholesterol out of arteries where it did not belong.
Now it seems that instead of directly reducing heart disease risk, high HDL levels may be a sign that something else is going on that makes heart disease less likely. To investigate the relationship between HDL and cardiovascular risk, the researchers, led by Dr. Sekar Kathiresan, director of preventive cardiology at Massachusetts General Hospital and a geneticist at the Broad Institute of M.I.T. and Harvard, used a method known as Mendelian randomization. It is a study design that has recently become feasible with the advent of quick and lower-cost genetic analyses.
The study found, as expected, that gene variations that raise LDL increase risk and those that lower LDL decrease risk. The gene effects often were tiny, altering LDL levels by only a few percent. But the data, involving tens of thousands of people, clearly showed effects on risk.
“That speaks to how powerful LDL is,” Dr. Kathiresan said.
But the HDL story was very different. First the investigators looked at variations in a well-known gene, endothelial lipase, that affects only HDL. About 2.6 percent of the population has a variation in that gene that raises their HDL levels by about 6 points. The investigators looked at 116,000 people, asking if they had the variant and if those who carried the HDL-raising variant had lower risk for heart disease.
“We found absolutely no association between the HDL-boosting variant and risk for heart disease,” Dr. Kathiresan said. “That was very surprising to us.”

So, if these results are to be believed, it is still very important to lower LDL--that can save your life, as expected. But, trying to do alter your HDL may just be a waste of time.