HDL Dysfunction Is Associated With an Increased Risk of Acute Coronary Syndrome

Maria Trinidad Soria-Florido et al. published the results of their study on high-density lipoprotein (HDL) function and coronary syndrome in Circulation. They showed that low amount of HDL sphingosine-1-phosphate (S1P) and apolipoprotein A-I and low cholesterol efflux capacity are associated with cardiovascular manifestations of angina. HDL function was studied by measuring cholesterol efflux capacity, S1P, and ApoA-I in apolipoprotein B-depleted plasma and they showed that impaired cholesterol function is associated with a higher risk of acute coronary syndrome (ACS), irrespective of HDL cholesterol (HDL-C) concentrations.

The investigators selected a subgroup of patients who were participating in PREDIMED study, which was a randomized clinical trial including patients with high cardiovascular risk factors to evaluate the effects of following a traditional Mediterranean Diet (TMD) on the primary prevention of cardiovascular outcomes. The primary endpoints were decided to be fatal or non-fatal myocardial infarction and/or fatal or non-fatal unstable angina. The committee responsible to adjudicate the events was blinded to the treatment. Dr. Trinidad et. al. implemented a nested 1:2 case-control design, matching two controls by age (±5 years), sex, body mass index, intervention group, and time-to-event. They obtained apolipoprotein B-depleted plasma samples and measured the HDL related activity in the sample.

The findings showed that except for plasma HDL-C concentrations and the levels of ApoA-I in HDL, all other HDL related biomarkers correlated weakly with each other. There was an almost linear correlation between all HDL related biomarkers (except for ApoA-IV) and the incidence of cardiovascular events. They also showed that there is a strong relationship between low cholesterol efflux capacity (CEC) and a higher incidence of myocardial infarction.

Previous studies have shown that there is an association between low CEC and ACS in hypertriglyceridemia patients, but Maria Trinidad Soria-Florido et al. showed that this association also exists in patients with normal triglyceride levels. Hypertriglyceridemia probably exaggerates the effect. They also showed that not only HDL-bound S1P can predict atherosclerotic lesions development and its extent, but also S1P levels in apolipoprotein B-depleted plasma is associated inversely with ACS risk.

The study was limited by the small sample size and lack of thorough evaluation of the HDL oxidative-inflammatory index.