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Cardio IQ Lipoprotein Fractionation, Ion Mobility

Cardio IQ Lipoprotein Fractionation, Ion Mobility

Test Summary

Cardio IQ® Lipoprotein Fractionation, Ion Mobility

  

Clinical Use

  • Determine cardiovascular disease (CVD) risk

Clinical Background

Elevated levels of low-density lipoprotein cholesterol (LDL-C) and reduced levels of high-density lipoprotein cholesterol (HDL-C) contribute to CVD events. However, these markers tell only part of the story. For example, in patients hospitalized for coronary artery disease (CAD), almost 50% have normal levels of LDL-C (<100 mg/dL) and approximately 20% have normal levels of both LDL-C and HDL-C (≥40 mg/dL).1 The residual risk in patients with CAD and normal levels of LDL-C and HDL-C has prompted evaluation of lipoprotein subfractions in the hope that they will provide a more accurate risk assessment for all patients.

Indeed, a number of prospective studies have found that lipoprotein subfractions are associated with CVD events.2,3 Some studies even suggest that lipoprotein subfraction measurements add value to standard lipid measurements, though others do not (see review by Krauss4). This apparent discrepancy could be due to different methods of measurement, which include vertical ultracentrifugation, nuclear magnetic resonance, gradient gel electrophoresis, and ion mobility. All but ion mobility use algorithms to indirectly calculate concentrations. In contrast, the ion mobility method, also known as gas-phase electrophoretic mobility, is the only one that directly measures particle size and concentration.5 And unlike some methods, ion mobility separation of subfractions does not cause lipoprotein modification that could potentially affect the accuracy of the assay.5 Ion mobility has been used in multiple lipoprotein studies2,3,6 and is the method used in the Cardio IQ Lipoprotein Fractionation, Ion Mobility test.

The ion mobility method has been used to specifically assess the relationship between lipoprotein subfraction levels and CVD events.2,3,6 In a prospective study of 4,594 initially healthy individuals, high LDL particle number and low LDL peak size were associated with increased CVD events. In the same study, incidence of CVD events was associated with a high level of LDL small- and LDL medium-sized particles and with a low level of HDL large-sized particles.3 These results are consistent with earlier observations that a predominance of small, dense LDL particles (known as pattern B, phenotype B, or small LDL trait) is associated with a 3-fold increased risk of myocardial infarction.7

Two other studies that used the ion mobility method also found an association between lipoprotein subfractions and CVD events. This association held true even after accounting for LDL-C, HDL-C, and triglyceride levels.2,6 One of these 2 studies investigated 1,928 individuals who were not classified into any of the 4 statin-benefit groups defined in the 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults.2,8 In this study, after a median follow-up of 16.4 years, patients in the top tertile of LDL particle number had greater than 2-fold risk of incident CVD compared with patients in the bottom tertile.2 The other study investigated over 11,000 individuals from the JUPITER trial, a study of patients who had LDL-C <130 mg/dL and high sensitivity C-reactive protein ≥2 mg/L. In the JUPITER trial, incident CVD was associated with LDL particle number (HR 1.18; 95% CI 1.03-1.36) and several LDL subfractions.6

Individuals Suitable for Testing

  • Individuals who have intermediate risk of CVD based on traditional or emerging risk factors

    –  Traditional risk factors include age (men >45 years; women >55 years [Framingham]), family history of CVD, hypertension, excessive alcohol use, smoking, obesity, and low HDL-C.

    –  Metabolic syndrome is also an indicator of intermediate risk.

  • Individuals who have a high risk of CVD based on traditional or emerging risk factors

    –  High risk includes established CVD, diabetes, and/or LDL-C ≥190.

  • Individuals being monitored for therapeutic response

Method

  • Ion mobility: gas-phase generation of singly-charged ions, separation of ions based on electrophoretic mobility, and detection of ions by light scattering
  • Analytical sensitivity: 0.4 nmol/L for HDL subfractions; 0.2 nmol/L for LDL subfractions

Reference Ranges

Reference ranges and risk cut points are provided in the Table.

Table. Reference Ranges and Risk for Lipoprotein Fractionation

Lipoprotein Subtype
(Size Range)

Reference Rangesa

 

Riska,b

Male

Female

 

Optimal

Moderate

High

LDL particle number

1,016-2,185

1,016-2,185

 

<1,260

1,260-1,538

>1,538c

LDL small (20.82-21.41 nm)

123-441

115-386

 

<162

162-217

>217c

LDL medium (21.41-22.0 nm)

167-465  

121-397

 

<201

201-271

>271c

HDL large (10.5-14.5 nm)

4,334-10,815

5,038-17,886

 

>9,386

9,386-6,996

<6,996c

LDL patternd

A

A

 

A

--

B

LDL peak size

≥218.2    

≥218.2    

 

>222.5

222.5-218.2

<218.2

a Ranges for LDL small, LDL medium, and HDL large are given in nmol/L; LDL peak size is given in Angstroms (Å).
b Adult cardiovascular event risk category cut points (optimal, moderate, high) are based on adult U.S. reference population. Risk of CVD events is based on a reanalysis (unpublished) of the data presented in Musunuru et al (reference 3).
c Relative risk and 95% confidence intervals for high vs optimal group are as follows: LDL particle number, 2.0 (1.59-2.52); LDL small, 2.06 (1.64-2.58); LDL medium, 2.02 (1.61-2.54); and HDL large, 0.41 (0.32-0.51).
d LDL pattern is based on predominant LDL peak particle size: ≥218.2 Å for phenotype A and <218.2 Å for phenotype B.

Interpretive Information

The following are consistent with a high risk of CVD events: 1) a high LDL particle number, 2) a high level of LDL small- or medium-sized particles, 3) a low level of HDL large-sized particles, or 4) a low LDL peak size (Table).

An LDL pattern B is consistent with a higher risk of CVD; an LDL pattern A (predominantly larger, more buoyant LDL particles) is consistent with a lower level of risk.

References

  1. Sachdeva A, Cannon CP, Deedwania PC, et al. Lipid levels in patients hospitalized with coronary artery disease: an analysis of 136,905 hospitalizations in Get With The Guidelines. Am Heart J. 2009;157:111-117.

  2. Melander O, Shiffman D, Caulfield MP, et al. LDL particle number is associated with incident atherosclerotic cardiovascular disease among persons with a 10-year risk of <7.5% [ATVB abstract A590]. Arterioscler Thromb Vasc Biol. 2014;34:A590.

  3. Musunuru K, Orho-Melander M, Caulfield MP, et al. Ion mobility analysis of lipoprotein subfractions identifies three independent axes of cardiovascular risk. Arterioscler Thromb Vasc Biol. 2009;29:1975-1980.

  4. Krauss RM. Lipoprotein subfractions and cardiovascular disease risk. Curr Opin Lipidol. 2010;21:305-311.

  5. Caulfield MP, Li S, Lee G, et al. Direct determination of lipoprotein particle sizes and concentrations by ion mobility analysis. Clin Chem. 2008;54:1307-1316.

  6. Mora S, Caulfield MP, Wohlgemuth J, et al. Lipoprotein subclasses by ion mobility and first cardiovascular events: an analysis of 11,227 participants from the JUPITER trial [ATVB abstract A630]. Arterioscler Thromb Vasc Biol. 2014;34:A630.

  7. Austin MA, Breslow JL, Hennekens CH, et al. Low-density lipoprotein subclass patterns and risk of myocardial infarction. JAMA. 1988;260:1917-1921.

  8. Stone NJ, Robinson J, Lichtenstein, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129:25 (suppl 2):S1-45.
     

 Content reviewed 01/2015
 

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