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 having a high baseline serum glucose level of at least 126 mg/dL and a baseline triglyceride level of about 200 mg/dL to 499 mg/dL, the method comprising administering to the subject a pharmaceutical composition comprising eicosapentaenoic acid or a derivative thereof and further comprising a step of determining a baseline oxidized sdLDL level in the subject prior to administering the pharmaceutical composition to the subject.
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 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.
6. The method of claim 5 , wherein the method further comprises administering atorvastatin and/or o-hydroxyatorvastatin to the subject.
7. The method of claim 6 , 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 atorvastatin and/or the o-hydroxyatorvastatin but not the pharmaceutical composition.
8. The method of claim 6 , 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.
9. The method of claim 1 , wherein the subject is on statin therapy, optionally stable statin therapy.
10. The method of claim 1 , wherein the subject is diabetic.
11. The method of claim 1 , wherein the high baseline serum glucose level is a fasting serum glucose level of at least 160 mg/dL.
12. The method of claim 1 , wherein the high baseline serum glucose level is a non-fasting serum glucose level of at least 200 mg/dL.
13. A method of treating or preventing atherosclerosis in a subject by reducing or preventing sdLDL oxidation in the subject, the method comprising administering to the subject a pharmaceutical composition comprising eicosapentaenoic acid or a derivative thereof, and further comprising determining a baseline oxidized sdLDL level in the subject prior to administering the pharmaceutical composition to the subject.