Abstract 18866: HDL Subclass Heterogeneity Relates to Differences in Risk of Incident Coronary Heart Disease
Background: Raising the cholesterol fraction of HDL particles is targeted as a cardiovascular disease reduction strategy. However, HDL particles are highly heterogeneous in composition and structure, which may relate to differences in their anti-atherogenic potential. We prospectively evaluated the association of HDL subclasses, as defined by a recently proposed nomenclature aimed to harmonize cross-comparison across different HDL subfractionation techniques, with the risk of incident coronary heart disease (CHD) in initially healthy women.
Methods: Baseline HDL subclass concentrations were measured and categorized into 5 groups (very large, large, medium, small, and very small) by nuclear magnetic resonance spectroscopy in 27 177 participants of the Women’s Health Study (median follow-up 17 years). First report of incident CHD (myocardial infarction, coronary revascularization, and CHD death) was ascertained (n=1 056 cases).
Results: Multivariable Cox regression HRs (95%CIs) adjusted for age, ethnicity, blood pressure, smoking, postmenopausal status, hormone therapy, and treatment assignment showed inverse associations with incident CHD for quartile 4 vs 1 concentrations of very large 0.50 (0.42-0.61), large 0.53 (0.44-0.62), and medium 0.69 (0.58-0.82) HDL subclasses (all p-trend<0.0001, Table). Conversely, small and very small HDL subclasses were associated with an increased risk: HRs 1.24 (1.03-1.48, p-trend=0.04) and 1.74 (1.45-2.08, p-trend<0.0001), respectively. After additionally adjusting for potential mediating factors (BMI, diabetes, and lipid/lipoprotein concentrations), only the large HDL subclass remained statistically significantly associated with CHD (p-trend=0.0004, Table).
Conclusion: In this prospective study of 27,177 initially healthy women followed for 17 years, associations with risk of incident CHD differed by HDL particle subclass, which may be relevant for the development of HDL-modulating therapies.
- © 2013 by American Heart Association, Inc.