Soria-Florido MT, Castañer O, Lassale C, et al. - Given that a clear association between HDL cholesterol and cardiovascular disease has not been established and this resulted in the formulation of a hypothesis that biological activity of HDL, instead of its cholesterol content, is responsible for its atheroprotective role, but no comprehensive inquiry has been conducted till date to inquire about the link between HDL functional characteristics and acute coronary syndrome, so, researchers addressed this subject in this case-control analysis nested within the PREDIMED (Prevención con Dieta Mediterránea) cohort, originally a randomized trial wherein participants followed a Mediterranean or low-fat diet. By gender, age, intervention group, body mass index, and follow-up time, individual matching (1:2) of 167 incident acute coronary syndrome cases to control patients was done. Two individual manifestations, ie, myocardial infarction and unstable angina, were assessed as secondary outcomes. Findings revealed that low cholesterol efflux capacity values, pro-oxidant/proinflammatory HDL particles, and low HDL levels of sphingosine-1-phosphate and apolipoprotein A-I were related to raised odds of acute coronary syndrome and its manifestations in people carrying a high cardiovascular risk.