Abstract 17839: High-Density Lipoprotein Particle Concentration and Size Are Markers of Residual Cardiovascular Risk in a Coronary Catheterization Cohort
Background: Residual risk beyond standard risk factors for cardiovascular (CV) events exists despite optimal control of those risk factors. Reduction of low-density lipoprotein cholesterol (LDL-C) with statin medication remains an important intervention for primary and secondary prevention of CV events. The role of high-density lipoprotein cholesterol (HDL-C) in residual CV risk is less clear, given that many interventions targeted to raise HDL-C have failed to reduce CV events. We hypothesized that HDL particle concentration (HDL-P) and size are associated with future CV events in a high-risk population after accounting for standard risk factors and might therefore serve as a potential additional CV risk targets.
Methods: The CATHGEN biorepository consists of subjects undergoing catheterization for clinical suspicion of ischemic heart disease at Duke University. The CV event rate was 30% at the time of this analysis. NMR analyses of lipoprotein particle concentration were performed in frozen plasma obtained from 4,248 CATHGEN subjects. Lipoprotein association with time to event [death/myocardial infarction (MI) or death] was tested by Cox proportional hazards adjusting for age, sex, race, diabetes, hypertension, hyperlipidemia, smoking status, body-mass index, LDL-C and HDL-C.
Results: After adjustment, HDL-P had a strong negative association with future CV events (hazard ratio and 95% confidence interval per 1.0 population standard deviation) for death (0.587 [0.544-0.633], χ2 4.01e-43) and death/MI (0.613 [0.571-0.659], χ2 6.62e-41). Greater large HDL particle concentration was associated with greater risk (death 1.72 [1.56-1.90], χ2 1.94e-26; death/MI 1.62 [1.48-1.78], χ2 1.3e-23) whereas greater small HDL particle concentration was protective for CV events (death 0.708 [0.667-0.752], χ2 5.16e-30; death/MI 0.716 [0.677-0.757], χ2 6.16e-32).
Conclusion: The favorable association of HDL on CV risk is complex and may relate more to HDL particle function rather than cholesterol content. The strong negative associations of HDL-P and small HDL particles with future CV events, even after adjustment for LDL-C and HDL-C, suggest that HDL-P and size may be important targets for management of residual CV risk in high-risk populations.
Author Disclosures: R.W. McGarrah: None. D.M. Craig: None. C. Haynes: None. Z.E. Dowdy: None. S.H. Shah: None. W.E. Kraus: None.
- © 2014 by American Heart Association, Inc.