High-density lipoprotein (HDL), or "good" cholesterol, normally protects against heart and artery disease by helping to keep blood vessels clear.
Yet trials have failed to show raising HDL levels in patients leads to signficant improvements in cardiovascular health.
A key protein in HDL, apoA1, that allows the molecule to remove "bad" cholesterol from artery walls becomes oxidised and joins forces with its harmful cousin. Blood tests conducted on 627 patients in the US showed higher levels of the dysfunctional HDL raised the risk of heart and artery disease.
"Identifying the structure of dysfunctional apoA1 and the process by which it becomes disease-promoting instead of disease- preventing is the first step in creating new tests and treatments for cardiovascular disease," said lead researcher Dr Stanley Hazen, from the Cleveland Clinic.
The research is reported in the latest edition of the journal Nature Medicine.