CHD risk stratification evaluations for subjects with high levels of large HDL-P

• US 10,386,355 B2
• Filed: 09/29/2016
• Issued: 08/20/2019
• Est. Priority Date: 04/27/2012
• Status: Active Grant

• Current Assignee: LipoScience, Inc. (Laboratory Corporation Of America Holdings)
• Original Assignee: LipoScience, Inc. (Laboratory Corporation Of America Holdings)
• Inventors: Otvos, James D., Shalaurova, Irina Y.
• Primary Examiner(s): Negin, Russell S
• Application Number:
  US15/280,086
• Publication Number:
  US 20170017772A1
• Time in Patent Office: 1,055 Days
• Field of Search: None
• CPC Class Codes: G01N 2800/325 Heart failure or cardiac arrest, e.g. cardiomyopathy, congestive heart failure
• CPC Class Codes: G01N 2800/50 Determining the risk of developing a disease
• CPC Class Codes: G01N 33/487 of liquid biological material
• CPC Class Codes: G01N 33/92 involving lipids, e.g. cholesterol , lipoproteins, or their receptors steroid hormones G01N33/743
• CPC Class Codes: G16H 20/10 relating to drugs or medications, e.g. for ensuring correct administration to patients
• CPC Class Codes: G16H 50/50 for simulation or modelling of medical disorders
• CPC Class Codes: G16H 50/70 for mining of medical data, e.g. analysing previous cases of other patients
• CPC Class Codes: G16Z 99/00 Subject matter not provided for in other main groups of this subclass

Abstract

Embodiments of the invention are directed to methods, systems and computer programs that provide improved risk stratification for people having elevated large HDL-P using at least one defined HDL risk interaction parameter.

Claims

1. A method of determining whether a subject with elevated concentrations of very large high density lipoprotein (HDL) particles (HDL-P) is at increased risk for a cardiac event and/or CHD, comprising:

providing a blood plasma or serum sample from the subject;

obtaining NMR signal data of the blood plasma or serum sample from the subject;

determining NMR derived concentration measurements of at least HP_VS, HP_ML, and HP_VL, where HP_VS is a concentration of very small HDL-P subclasses, HP_ML is a concentration of medium and large HDL-P subclasses, and HP_VL is a concentration of very large HDL-P subclasses;

identifying when a subject has an elevated concentration of HP_VL relative to a population norm, wherein the subject has an elevated concentration of HP_VL when the subject'"'"'s concentration is ≥

80% of a population norm; and

calculating at least one HDL interaction risk parameter associated with HDL content of a blood plasma or serum sample of the subject, the at least one HDL interaction risk parameter comprising at least two of HP_VS, HP_ML, and HP_VL.

2. The method of claim 1, wherein the at least one HDL interaction risk parameter comprises P1 or R1, or P1 and R1, wherein P1 is a product defined by HP_VS times HP_ML, and wherein R1 is a ratio defined by HP_VL/HP_ML.

3. The method of claim 2, the calculated at least one HDL interaction risk parameter includes P1/R1.

4. The method of claim 3, wherein a respective subject is identified as at risk for CHD if P1/R1 for the subject has a value in the first or second quartile of a population norm.

5. The method of claim 3, wherein a respective subject is identified as at risk for CHD if P1/R1 for the subject has a value ≤

170 μ

mol²/L².

6. The method of claim 2, further comprising generating a report based on the calculation of the at least one HDL interaction risk parameter that includes at least one of the following:

R1, P1, P1/R1, or P1+R1.

7. The method of claim 1, wherein the at least one HDL interaction risk parameter is at least one of the following:

(HP_VS)(HP_ML,)/(HP_VL), or ((HP_VS)(HP_ML)²)/(HP_VL), or (HP_ML)²/(HP_VL).

8. The method of claim 1, wherein the calculation of at least one HDL interaction risk parameter is electronically selectively carried out only when the subject has the elevated concentration of HP_VL.

9. The method of claim 1, further comprising:

screening subjects that may benefit from an HDL risk stratification test by (a) first identifying if the subject has elevated high density lipoprotein-cholesterol (HDL-C) that is at least one of;

≥

60 mg/dL, ≥

80 mg/dL, or ≥

100 mg/dL;

then (b) electronically identifying when the subject also has an elevated concentration of HP_VL that is ≥

80% of a population norm, and wherein the performing the calculation of at least one HDL interaction risk parameter is selectively carried out only if the subject has the elevated concentration of HP_VL.

10. The method of claim 1, wherein the HP_VS includes HDL subpopulations having an average diameter between 7.4 nm and 7.6 nm.

11. The method of claim 1, wherein the HP_ML includes HDL subpopulations having an average diameter between 8.3 nm and 10.9 nm.

12. The method of claim 1, wherein the HP_VL includes HDL subpopulations having an average diameter between 11 nm and 13.5 nm.

13. The method of claim 1, further comprising generating a report that visually and/or textually indicates whether the subject is at increased risk of CHD despite having elevated HP_VL.

14. The method of claim 1, further comprising electronically monitoring whether there is a change in the HDL risk interaction parameter over time to assess a change in CHD risk when HP_VL remains above 1.84 μ

mol/L.

15. The method of claim 1, further comprising referring the subject for further medical evaluation if the calculation indicates there is a likelihood of increased risk of CHD despite the elevated very large HDL-P.

16. The method of claim 1, wherein the subject is human, and wherein the obtaining and calculating steps are carried out using at least one processor, the method further comprising providing a report indicating whether the subject is at risk of having and/or developing CHD based, in part, on the calculation.

17. A computer program product for stratifying CHD risk for patients with elevated concentrations of very large high density lipoprotein (HDL) particles (HDL-P), the computer program product comprising:

a non-transitory computer readable storage medium having computer readable program code embodied in the medium, the computer-readable program code comprising;

computer readable program code that obtains NMR signal data of an in vitro blood plasma or serum sample of a subject to determine NMR-derived concentration measurements of at least twenty subpopulations of HDL-P subclasses in a blood plasma or serum sample;

computer readable program code for electronically identifying when the subject has an elevated concentration of HP_VL relative to a population norm, wherein the subject has an elevated concentration of HP_VL when the subject'"'"'s HP_VL concentration is ≥

80% of a population norm; and

computer readable program code that calculates at least one HDL interaction risk parameter associated with HDL content of a blood plasma or serum sample of the subject, the at least one HDL interaction risk parameter comprising at least two of HP_VS, HP_ML, and HP_VL, where HP_VS is a concentration of very small HDL-P subclasses, HP_ML is a concentration of medium and large HDL-P subclasses, and HP_VL is a concentration of very large HDL-P subclasses.

18. A system for analyzing CHD risk, comprising:

a circuit comprising at least one processor configured to determine whether a subject with elevated concentrations of very large high density lipoprotein (HDL) particles (HDL-P) is at increased risk for a cardiac event and/or CHD, the at least one processor configured to

obtain NMR signal data of an in vitro blood plasma or serum sample of the subject,

determine NMR-derived concentration measurements for HP_VS, HP_ML, and HP_VL, where HP_VS is a concentration of very small HDL-P subclasses, HP_ML is a concentration of medium and large HDL-P subclasses, and HP_VL is a concentration of very large HDL-P subclasses,

identify when the subject has an elevated concentration of HP_VL relative to a population norm, wherein the subject has an elevated concentration of HP_VL when the subject'"'"'s HP_VL concentration is ≥

80% of a population norm; and

calculate at least one HDL interaction risk parameter associated with HDL content of a blood plasma or serum sample of the subject, the at least one HDL interaction risk parameter comprising at least two of HP_VS, HP_ML, and HP_VL.