High-Density Lipoprotein Particle Subclass Heterogeneity and Incident Coronary Heart Disease

Study Questions:

High-density lipoprotein (HDL) particles are heterogeneous in composition and structure, which may relate to differences in anti-atherosclerotic potential at any level of HDL cholesterol. What is the association of HDL subclasses with incident coronary heart disease (CHD)?


Baseline HDL particle concentrations were measured by nuclear magnetic resonance spectroscopy and categorized into five subclasses (very large, large, medium, small, and very small) among 26,332 initially healthy women in this prospective study. During a median follow-up of 17 years, 969 cases of incident CHD (myocardial infarction, revascularization, and CHD death) were ascertained.


Incident CHD was associated with age, blood pressure, menopausal status, body mass index, diabetes, and each of the lipids and apolipoprotein (apo). In Cox models that adjusted for clinical variables, associations with incident CHD were inverse (p trend < 0.0001) for concentrations of very large (hazard ratio [HR] for top vs. bottom quartile, 0.49; 95% confidence interval [CI], 0.41-0.60), large (HR, 0.54; CI, 0.45-0.64), and medium (HR, 0.69; 95% CI, 0.58-0.83) HDL subclasses. Conversely, HRs for small and very small HDL were 1.22 (1.01-1.46; p trend = 0.08) and 1.67 (1.39-2.02; p trend < 0.0001), respectively. However, after additionally adjusting for metabolic and lipoprotein variables, associations for the spectrum of large, medium, and small HDL subclasses were inverse (p trend < 0.05 for large and small and 0.07 for medium), whereas subclasses at either end of the spectrum were not associated with CHD (p trend = 0.97 for very large and 0.21 for very small HDL).


In this prospective study, associations with incident CHD differed by HDL particle subclass, which may be relevant for developing HDL-modulating therapies.


The incident CHD of 2/1,000 per year in the women may be too low to draw conclusions about the clinical importance of HDL subclasses. Interestingly, event rates in women with an apo B <90 mg/dl was 1.4% versus 5.9% with an apo B ≥90 mg/dl, and the associations with HDL subclass were only significant in those with an apo B ≥90 mg/dl.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Atherosclerotic Disease (CAD/PAD), Lipid Metabolism, Nonstatins

Keywords: Coronary Artery Disease, Myocardial Infarction, Women's Health, Apolipoprotein A-I, Coronary Disease, Blood Pressure, Dyslipidemias, Body Mass Index, Biological Markers, Gadiformes, Cardiovascular Diseases, Cholesterol, HDL, Confidence Intervals, Diabetes Mellitus

< Back to Listings