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US 11,442,072 B2Granted
Method for measuring LDL aggregation
AssigneeJenny and Antti Wihuri Foundation
InventorsKatariina Öörni, Maija Ruuth, Petri Kovanen
Life of this patent
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Abstract
The present disclosure relates to a method for measuring aggregation of low-density lipoprotein (LDL). The susceptibility of LDL to aggregate is an important factor regarding prognosis, diagnosis and surveillance of atherosclerotic cardiovascular diseases and cardiometabolic diseases, such as type 2 diabetes and related conditions, at various stages of their development. Also provided are methods of treatment of such diseases in subjects in need thereof.
Claims18
A method of determining a presence or risk of an atherosclerotic cardiovascular disease (ASCVD) or a cardiometabolic disease in a human subject, the method comprising:
- providing LDL particles from a blood plasma or serum sample of the human subject;
- mixing the LDL particles with a sphingomyelinase enzyme in a solution at acidic pH;
- detecting formation of LDL aggregates in the solution, and
- measuring the sizes of the detected LDL aggregates,
- wherein the detected LDL aggregates have a median size of at least 200 nm and the human subject is determined to have or be at risk for developing an ASCVD or a cardiometabolic disease.
2 more elements
A method comprising:
- providing a human plasma or serum sample;
- mixing the human plasma or serum sample with a sphingomyelinase enzyme at acidic pH;
- detecting formation of LDL aggregates in the sample, and
- measuring the sizes of the detected LDL aggregates.
1 more element
A method comprising:
- providing LDL particles from a blood plasma sample of a human subject that has been taking a cholesterol lowering medication selected from the group consisting of HMG CoA reductase inhibitor, a selective cholesterol absorption inhibitor, and a bile-acid binding resin;
- mixing the LDL particles with sphingomyelinase enzyme in a solution at acidic pH;
- detecting formation of LDL aggregates in said solution;
- measuring the sizes of the detected LDL aggregates;
- and
- if the LDL aggregates have a median size of at least 500 nm, continue administering to the human subject a therapeutically effective amount of the cholesterol lowering medication in combination with a healthy Nordic diet, a low sucrose diet, or a Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) inhibitor;
- and
- if the LDL aggregates have a median size of below 500 nm, continue administering to the human subject a therapeutically effective amount of the cholesterol lowering medication.
5 more elements
A method comprising:
- providing LDL particles from a blood plasma sample of a human subject that has been taking a cholesterol lowering medication selected from the group consisting of HMG CoA reductase inhibitor, a selective cholesterol absorption inhibitor, and a bile-acid binding resin;
- mixing the LDL particles with sphingomyelinase enzyme in a solution at acidic pH;
- detecting formation of LDL aggregates in said solution;
- measuring the sizes of the detected LDL aggregates;
- and
- if the LDL aggregates have a median size of at least 500 nm, continue administering to the human subject a therapeutically effective amount of the cholesterol lowering medication in combination with a healthy Nordic diet, a PCSK9 inhibitor, or a plant stanol or plant stanol ester;
- and
- if the LDL aggregates have a median size of below 500 nm, continue administering to the human subject a therapeutically effective amount of the cholesterol lowering medication.
5 more elements
A method comprising:
- providing LDL particles from blood plasma or serum samples of (a) a human subject at risk for developing ASCVD or a cardiometabolic disease and (b) a control human subject who is known to not have ASCVD or a cardiometabolic disease;
- mixing the LDL particles with a sphingomyelinase enzyme in a solution at acidic pH;
- detecting formation of LDL aggregates in the solution;
- measuring the sizes of the detected LDL aggregates every 15 to 30 minutes for up to 6 hours after mixing the LDL particles with the sphingomyelinase enzyme, and
- comparing the sizes of the detected LDL aggregates of the human subject at risk for developing ASCVD or a cardiometabolic disease with the sizes of LDL aggregates of the control human subject.
2 more elements
Dependencies are inferred from the claim text.