Physicians' Academy for Cardiovascular Education

No association between HDL particle concentration and MACE after ACS

Association of HDL particle concentration with cardiovascular risk following acute coronary syndrome: A case-cohort analysis of the dal-Outcomes trial

Salahuddin T, et al.

Literature - - Am Heart J 2019,

Introduction and methods

Concentration of high density lipoprotein cholesterol (HDL-C) is inversely associated with risk of coronary heart disease, epidemiologic studies show. However, it has also been shown that HDL-C concentration is not a reliable predictor of occurrence of major adverse cardiovascular events (MACE) in patients with established coronary heart disease.. Raising HDL-c by medication in clinical trials has not resulted in reduction of MACE, particularly when patients were using statins [1-3]. Data from cohort studies and clinical trials haver suggested that total HDLP is a better indicator of HDL-c function than HDL-c concentration and thus a better predictor of MACE [4-7]. Also, the distribution of HDL particles may contribute to an improved CV risk prediction.

The present study investigated whether total HDL particle (HDLP) concentration, as compared to HDL-C, is a better predictor of MACE in ACS patients.

The present study investigated a nested case-cohort subgroup of patients that participated in the randomized controlled dal-OUTCOMES trial. The trial cohort consisted of 15,871 patients with recent ACS. Patients in the trial cohort, of which 97% used statins, were randomly assigned, between 4 and 12 weeks after ACS, to receive 600 mg of cholesteryl ester transfer protein (CETP) inhibitor dalcetrapib (which raises HDL-C and HDLP levels) orally twice daily or matching placebo. The primary outcome, time to first occurrence of MACE, defined as coronary heart disease death, non-fatal myocardial infarction, ischemic stroke, hospitalization for unstable angina, or resuscitated cardiac arrest. was not decreased with dalcetrapib compared to placebo .

The case-cohort subgroup of the present study included 1378 unique subjects: 476 cases (patients with a primary endpoint event) and 902 controls who were event-free at the time of a case event and had the same type of index ACS as the case. In these patients, total HDLP, small, medium and large HDLP, low-density particles (LDLP) and very low-density particles (VLDLP), HDL-C, LDL-C and triglyceride concentrations were measured by nuclear magnetic resonance (NMR) spectroscopy at baseline (4-12 weeks after ACS) (1378 subjects) and after 3 months (1203 subjects). Median follow-up of cases and controls was 28 months.

This study investigated whether (changes in) HDLP concentration predicted MACE, , as well as association between HDLP subclasses and MACE and including HDL-C. Also, interaction of assigned study treatment with HDLP or HDL-c on MACE was studied.

Main results

there was no interaction of treatment assignment with baseline to month 3 change in HDLP or HDL-C on MACE.


In this study, HDLP and HDL-c were were not associated with MACE in patients after an ACS event in a population well-treated with statins.


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Find this article online at Am Heart J

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