Methods of reducing or preventing oxidation of small dense LDL or membrane polyunsaturated fatty acids
In various embodiments, the present invention provides methods of treating and/or preventing cardiovascular-related disease and, in particular, a method of reducing or preventing small dense LDL (“sdLDL”) oxidation in a subject, the method comprising administering to the subject a pharmaceutical composition comprising eicosapentaenoic acid or a derivative thereof.
1. A method of treating a cardiovascular-related disease in a subject having glucose levels of at least about 200 mg/dL, the method comprising:
(a) measuring a baseline level of membrane cholesterol domain formation and a baseline level of oxidative modification of membrane polyunsaturated fatty acids in the subject prior to step (b); and
(b) administering to the subject a pharmaceutical composition comprising at least 80%, by weight of all fatty acids (and/or derivatives thereof) that are present in the composition, eicosapentaenoic acid or a derivative thereof,
wherein the administering to the subject the pharmaceutical composition reduces the membrane cholesterol domain formation in the subject by between 10% and 100% compared to the baseline level, and
wherein the administering to the subject the pharmaceutical composition reduces the oxidative modification of membrane polyunsaturated fatty acids in the subject by between 10% and 100% compared to the baseline level.
2. The method of claim 1 , wherein the pharmaceutical composition comprises eicosapentaenoic acid or a derivative thereof, wherein an amount of the eicosapentaenoic acid or derivative thereof present in the pharmaceutical composition is selected from the group consisting of at least 90%, at least 95%, and at least 96%, by weight of all fatty acids (and/or derivatives thereof) that are present in the composition.
3. The method of claim 1 , wherein the pharmaceutical composition comprises no docosahexaenoic acid or esters thereof.
4. The method of claim 1 further comprising measuring a second level of membrane cholesterol domain formation and a second level of oxidative modification of membrane polyunsaturated fatty acids in the subject after administering to the subject the pharmaceutical composition.
5. The method of claim 4 , wherein the second level of membrane cholesterol domain formation and oxidative modification of membrane polyunsaturated fatty acids is between 10% and 100% lower than the baseline level.