Despite plenty of evidence that people with low levels of HDL cholesterol are more prone to heart attacks, a large new study suggests that the lacking lipid is not to blame.
The analysis of data on nearly 70,000 people in Denmark affirmed the link between low levels of high-density lipoprotein (HDL) cholesterol and raised heart attack risk in the general population. But in people with a gene mutation that lowers HDL, heart attack risk was not found to be higher at all.
Association itself doesn't mean causality, said lead author Dr Ruth Frikke-Schmidt, a consultant in the Department of Clinical Biochemistry at Rigshospitalet in Copenhagen.
The results, published online November 16 in the Journal of Clinical Endocrinology and Metabolism, indicate that just having low HDL is not what raises the likelihood of a heart attack.
Difficult to study and isolate DHL cholesterol
"People with low 'good' cholesterol also have a whole bunch of other factors that relate to heart disease," said Dr Christopher Cannon, professor of medicine at Harvard Medical School and editor of the American College of Cardiology's website.
It's difficult to study and isolate HDL cholesterol, added Cannon, who was not involved in the new study. People with low HDL often suffer from obesity, high blood pressure and diabetes and sometimes have higher levels of LDL, he said.
To try to isolate the effects of HDL itself, Dr Frikke-Schmidt and her colleagues focused on people with a well-known variant of a gene called LCAT, which lowers HDL levels and occurs in about four percent of the population.
The variant gene is used as a stand-in for low HDL, she noted, but people with the variant don't necessarily have the other risk factors that usually affect HDL levels in the larger population.
A total relook
In the new study, a 13% decrease in HDL relative to average levels in the population was linked to an 18% increase in heart attack risk – if the low HDL was not explained by a gene variant. For people with the variant gene, the same HDL reduction was not linked to any increased risk of heart attack.
The findings add to a growing body of research that's making cardiologists second-guess what they've thought for decades, Dr Cannon told Reuters Health.
It's a total relook at what we thought was gospel, he said.
The findings fit in with Dr Frikke-Schmidt's earlier research showing that two other genetic variants that lower HDL cholesterol levels are not associated with an increased risk of heart disease.
Raise HDL cholesterol by exercising
According to both Dr Frikke-Schmidt and Cannon, the debate is particularly important, because there are currently drugs in trials that would raise HDL cholesterol.
If low HDL is not a cause of heart attacks, raising HDL may not be protective, they point out. Ruling out low levels of HDL cholesterol, Dr. Frikke-Schmidt said the most likely cause of the increased risk is remnant lipoproteins.
Until the real mechanisms are sorted out, Dr Cannon said it's still important for people to try and raise their HDL cholesterol by exercising and losing weight.
Beyond that there are so many question marks, he said. We're kind of in a wait and see mode.
(Reuters Health, December 2011)