Abstract 20297: Overloaded High Density Lipoprotein Particles & Incident Cardiovascular Events
Background: Increased high-density cholesterol content (HDL-C) indexed to HDL particle concentration (HDL-P), termed “cholesterol overloaded HDL,” has been associated with subclinical atherosclerosis in a low risk cohort. However, it remains unclear how indices of HDL composition associate with incident atherosclerotic cardiovascular disease (ASCVD) events and cholesterol efflux, a key anti-atherosclerotic pathway. HDL particle size is also considered an important parameter but has not been studied indexed to particle concentration.
Methods: HDL-C, HDL-P, and HDL particle size by NMR, and cholesterol efflux capacity from macrophages to apolipoprotein B-depleted plasma at baseline were measured in 2417 participants, ages 30 to 65, enrolled in the Dallas Heart Study, a probability based population sample. The associations of two indexes of HDL composition, HDL-C/HDL-P and HDL size/HDL-P, were assessed using multivariable Cox proportional hazards models. The primary ASCVD endpoint included first myocardial infarction, nonfatal stroke, coronary revascularization, or cardiovascular death.
Results: In a fully adjusted model that included traditional risk factors, the highest versus lowest quartiles of HDL-C/HDL-P and HDL-Size/HDL-P were both associated with a significant increase in incident ASCVD (HDL-C/HDL-P: HR 2.12, 95% CI 1.18 - 3.80; HDL-Size/HDL-P: HR 1.89, 95% CI 1.17 to 3.05). Cholesterol efflux capacity was inversely associated with HDL-Size/HDL-P (p=0.012) but not with HDL-C/HDL-P (p=0.517).
Conclusion: Overloaded HDL, as measured by increased HDL-C/HDL-P or HDL size/HDL-P, associates with an increased risk of incident ASCVD and may partially reflect dysfunctional HDL as assessed by lower cholesterol efflux. These findings highlight the importance of comprehensive assessment of HDL composition markers for ASCVD risk.
Author Disclosures: T. Sperry: None. A. Rohatgi: Research Grant; Significant; Merc. Consultant/Advisory Board; Modest; Cleveland Heartlabs, Inc., CSL, Consultant. A. Khera: None. I. Neeland: None. P. Joshi: None. C. Ayers: None.
- © 2016 by American Heart Association, Inc.