HDL laboratory test

High Density Lipoprotein Microchapters
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rim Halaby, M.D. [2]

Synonyms and keywords: HDL-C, HDL-P

Overview

The association between HDL levels and cardiovascular outcomes, especially in statin treated high risk patient with residual cardiovascular risks, has triggered a large interest in conducting trials for the evaluation of HDL lowering drugs. HDL is one of the most complicated and heterogeneous among the different lipoproteins as HDL subfractions can largely vary in function, structure, size, cholesterol and triglyceride contents. The widely used method of measurement of HDL is done through the chemical measurement of HDL-cholesterol ( HDL-c); however, recent evidence suggests that HDL-c might not be the best method to quantify HDL and study its relationship with cardiovascular outcomes in statin treated patients. Newer studies postulate that HDL-particles (HDL-p) might be a better measure for HDL's effect on residual cardiovascular risks.

HDL Measures

HDL-C

• HDL-cholesterol (HDL-C) has long been used to quantify HDL; in fact, HDL-C is measured according to its density on ultracentrifugation which ranges between 1.063 and 1.21 g/L.
• HDL is very heterogeneous in structure, size and proportion of cholesterol and triglycerides; hence, it has been hypothesized that HDL-C might not be the best method to measure HDL functionality and study its association with cardiovascular risk factor.

HDL-P

• HDL-particles (HDL-P) refers to the sum of the concentration of all the subfractions of HDL. HDL-P can be measured by nuclear magnetic resonance spectroscopic analysis or by ion mobility. However, these two modalities of measuring HDL-P have not been proven to give identical results; and hence there is no standardized modality to measure HDL-P yet.

• A recent study published in September 2013 suggests that HDL particle number (HDL-P) might be a better tool to assess HDL levels and its association with residual cardiovascular outcomes in patients treated with statin. This study relied on data from JUPITER trial ( Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin trial) where HDL size, HDL-P, HDL-C and apolipoprotein A-I level were measured in a population of 10886 participants. The results of this study revealed that HDL-P correlates better with coronary vascular disease than does HDL-C in statin treated participants. HDL-P and HDL-C equally correlate with coronary vascular disease in patients not treated with statin. In addition, MESNA ( Multi-Ethnic Study of Atherosclerosis) reported that, decreased levels of HDL-P correlates with an increased risk of higher intima-medial thickness of the carotid artery while HDL-C was no longer associated with intima-medial thickness of the carotid artery after adjustment for LDL-P and each other.
• The identification of an accurate method to clinically measure HDL has tremendous importance, especially that a lot of trials investigating new HDL increasing therapies are ongoing.

HDL Measurement Modalities

Chemical Measurements

Chemical measurements can be used to estimate HDL concentrations present in a blood sample, though such measurements may not indicate how well the HDL particles are functioning to reverse transport cholesterol from tissues. HDL-cholesterol (HDL-C) is measured by first removing LDL particles by aggregation or precipitation with divalent ions (such as Mg++) and then coupling the products of a cholesterol oxidase reaction to an indicator reaction. The measurement of apo-A reactive capacity can be used to measure HDL cholesterol but is thought to be less accurate.

Electrophoresis Measurements

Since the HDL particles have a net negative charge and vary by size, electrophoresis measurements have been utilized since the 1960s to both indicate the number of HDL particles and additionally sort them by size. Larger HDL particles are carrying more cholesterol.

NMR Measurements

The newest methodology for measuring HDL particles, available clinically since the late 1990s uses nuclear magnetic resonance fingerprinting of the particles to measure both concentration and sizes. This methodology was pioneered by researcher Jim Otvos and the North Carolina State University academic research spinoff company and dramatically reduced the cost of HDL measurements.