No evidence to back the belief that higher levels of good cholesterol boost cardiovascular health, says study published in Lancet.
High concentrations of HDL are one of the big markers for blood tests.
They are monitored as much as low levels of "bad" cholesterol (low-density lipoprotein, or LDL) as a yardstick of dangerously clogged arteries.
The paper used a method called mendelian randomisation to compare heart-attack risk among people who inherited known genetic variants that gave them higher HDL levels.
According to conventional wisdom, these individuals would have a lower risk of a coronary.
But the study, which looked at nearly 12,500 people with a history of a heart attack and over 41,000 otherwise healthy counterparts, found this was not always the case.
The results are important because of the use of drugs, sometimes inflicting side effects, which are administered to boost HDL cholesterol levels.
"These results show that some ways of raising HDL cholesterol might not reduce risk of myocardial infarction [heart attack] in human beings," said Sekar Kathiresan of Massachusetts General Hospital and Harvard Medical School.
"Therefore, if an intervention such as a drug raises HDL cholesterol, we cannot automatically assume that risk of myocardial infarction will be reduced."
In contrast, the study said "bad" cholesterol remained an accurate marker of cardiac risk.
Separately, a study, also carried in Thursday's Lancet, confirmed the benefits of LDL-lowering statins for protecting people with no previous history of cardiovascular disease.