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 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 reducing or preventing sdLDL oxidation in a subject in need thereof, the method comprising administering to the subject a pharmaceutical composition comprising eicosapentaenoic acid or a derivative thereof.
2 . The method of claim 1 , wherein the pharmaceutical composition comprises at least 80%, at least 90%, at least 95%, or at least 96%, by weight of all fatty acids (and/or derivatives thereof) present, eicosapentaenoic acid or a derivative thereof.
3 . The method of claim 1 , wherein the pharmaceutical composition comprises no docosahexaenoic acid or esters thereof.
4 . The method of claim 1 , wherein the reduction or prevention occurs by a free radical chain-breaking mechanism.
5 . The method of claim 1 further comprising determining a baseline oxidized sdLDL level in the subject prior to administering to the subject the pharmaceutical composition.
6 . The method of claim 5 further comprising determining a second oxidized sdLDL level in the subject after administering to the subject a pharmaceutical composition comprising eicosapentaenoic acid or a derivative thereof, wherein the second oxidized sdLDL level is not greater than, not significantly greater than, or lower than the baseline oxidized sdLDL level and/or wherein the second oxidized sdLDL level is not greater than, not significantly greater than, or lower than the baseline oxidized sdLDL level in comparison to a second subject who has not received the pharmaceutical composition.
7 . The method of claim 6 , wherein the method further comprises administering o-hydroxyatorvastatin to the subject.
8 . The method of claim 7 , wherein the second oxidized sdLDL level is not greater than, not significantly greater than, or lower than the baseline oxidized sdLDL level in comparison to a second subject who has received the o-hydroxyatorvastatin but not the pharmaceutical composition.
9 . The method of claim 7 , wherein the second oxidized sdLDL level is not greater than, not significantly greater than, or lower than the baseline oxidized sdLDL level in comparison to a second subject who has received the pharmaceutical composition but not the o-hydroxyatorvastatin.
10 . The method of claim 1 , wherein the subject has a baseline triglyceride level of at least 500 mg/dL.
11 . The method of claim 1 , wherein the subject has a baseline triglyceride level of about 200 mg/dL to 499 mg/dL.
12 . The method of claim 11 , wherein the subject is on statin therapy, optionally stable statin therapy.
13 . The method of claim 1 , wherein the subject is hyperglycemic or is diabetic.
14 . A method of reducing or preventing membrane cholesterol domain formation and/or reducing or preventing oxidative modification of membrane polyunsaturated fatty acids in a subject, the method comprising administering to the subject a pharmaceutical composition comprising eicosapentaenoic acid or a derivative thereof.
15 . The method of claim 14 , wherein the pharmaceutical composition comprises at least 80%, at least 90%, at least 95%, or at least 96%, by weight of all fatty acids (and/or derivatives thereof) present, eicosapentaenoic acid or a derivative thereof.
16 . The method of claim 14 , wherein the pharmaceutical composition comprises no docosahexaenoic acid or esters thereof.
17 . The method of claim 14 , wherein the reduction or prevention occurs by a free radical chain-breaking mechanism.
18 . The method of claim 14 further comprising measuring membrane cholesterol domain formation in the subject prior to administering to the subject the pharmaceutical composition.
19 . The method of claim 18 further comprising measuring membrane cholesterol domain formation in the subject after administering to the subject the pharmaceutical composition.
20 . The method of claim 14 , wherein the subject is hyperglycemic or is diabetic.