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High-density lipoprotein subclass measurements improve mortality risk prediction, discrimination and reclassification
Robert W McGarrah1, Damian M Craig2, Carol Haynes2
1Division of Cardiology, Department of Medicine, Durham, NC, USA; Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA.
Insights
HDL particle concentration (HDL-P) and smaller HDL subclasses are better predictors of mortality risk than HDL cholesterol (HDL-C) in high-risk cardiovascular disease patients. These measures improve risk assessment and could guide future therapies.
Area of Science:
- Cardiovascular Medicine
- Biochemistry
- Clinical Risk Assessment
Background:
- HDL cholesterol (HDL-C) raising therapies have failed to prevent cardiovascular disease (CVD).
- HDL's atheroprotective effects depend on particle characteristics beyond HDL-C levels.
- Novel HDL metrics are needed for accurate CVD risk assessment.
Purpose of the Study:
- To determine the association of HDL particle concentration (HDL-P) and HDL subclasses with mortality in high-risk CVD patients.
- To examine the clinical utility of HDL-P and subclasses in mortality risk discrimination and reclassification.
Main Methods:
- Nuclear magnetic resonance spectroscopy was used to measure HDL-P and HDL subclasses in 3972 individuals.
- Association with all-cause mortality was tested in multivariable models.
- The incremental utility of HDL subclasses for risk discrimination and reclassification was examined.
Main Results:
- HDL-P showed a stronger inverse association with mortality than HDL-C (HR 0.71 vs. 0.93).
- Smaller HDL subclasses (MS-HDL-P) were inversely associated with mortality, while larger HDL size conferred greater risk.
- MS-HDL-P fully accounted for the inverse relation of HDL-P with mortality; HDL-C was not significant after adjustment for MS-HDL-P.
- Adding MS-HDL-P to the GRACE Risk Score improved risk discrimination and reclassification.
Conclusions:
- HDL-P and smaller HDL subclasses are independent markers of residual mortality risk in high-risk CVD populations.
- These measures provide additional value beyond HDL-C for risk stratification.
- HDL-P and subclasses should be considered for risk assessment and development of HDL-targeted therapies.
Background And Aims:
Recent failures of HDL cholesterol (HDL-C)-raising therapies to prevent cardiovascular disease (CVD) events have tempered the interest in the role of HDL-C in clinical risk assessment. Emerging data suggest that the atheroprotective properties of HDL depend on specific HDL particle characteristics not reflected by HDL-C. The purpose of this study was to determine the association of HDL particle concentration (HDL-P) and HDL subclasses with mortality in a high-risk cardiovascular population and to examine the clinical utility of these parameters in mortality risk discrimination and reclassification models.
Methods:
Using nuclear magnetic resonance spectroscopy, we measured HDL-P and HDL subclasses in 3972 individuals enrolled in the CATHGEN coronary catheterization biorepository; tested for association with all-cause mortality in robust clinical models; and examined the utility of HDL subclasses in incremental mortality risk discrimination and reclassification.
Results:
Over an average follow-up of eight years, 29.6% of the individuals died. In a multivariable model adjusted for ten CVD risk factors, HDL-P [HR, 0.71 (0.67-0.76), p = 1.3e-24] had a stronger inverse association with mortality than did HDL-C [HR 0.93 (0.87-0.99), p = 0.02]. Larger HDL size conferred greater risk and the sum of medium- and small-size HDL particles (MS-HDL-P) conferred less risk. Furthermore, the strong inverse relation of HDL-P levels with mortality was accounted for entirely by MS-HDL-P; HDL-C was not associated with mortality after adjustment for MS-HDL-P. Addition of MS-HDL-P to the GRACE Risk Score significantly improved risk discrimination and risk reclassification.
Conclusion:
HDL-P and smaller HDL subclasses were independent markers of residual mortality risk and incremental to HDL-C in a high-risk CVD population. These measures should be considered in risk stratification and future development of HDL-targeted therapies in high-risk populations.
