Vitamin E supplementation reduces cardiovascular events in a subgroup of middle-aged individuals with both type 2 diabetes mellitus and the haptoglobin 2-2 genotype: A prospective double-blinded clinical trial

Arteriosclerosis, Thrombosis, and Vascular Biology

Volumn 28, Issue 2, 2008, Pages 341-347

  Milman, Uzi ^a   Blum, Shany ^b   Shapira, Chen ^a   Aronson, Doron ^c   Miller Lotan, Rachel ^b   Anbinder, Yefim ^b   Alshiek, Junia ^b   Bennett, Lawrence ^a   Kostenko, Maria ^a   Landau, Michele ^d   Keidar, Shlomo ^c   Levy, Yishai ^c   Khemlin, Alexander ^a   Radan, Arman ^a   Levy, Andrew P ^b  

^a CLALIT HEALTH SERVICES   (Israel)

^b TECHNION ISRAEL INSTITUTE OF TECHNOLOGY   (Israel)

^c RAMBAM MEDICAL CENTER   (Israel)

^d PharmaBrains Israel   (Israel)

Author keywords

Cardiovascular events; Diabetes mellitus; Haptoglobin genotype; Pharmacogenomics; Vitamin E

Indexed keywords

ACETYLSALICYLIC ACID; ALPHA TOCOPHEROL; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; HAPTOGLOBIN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; METFORMIN; PLACEBO;

ADULT; AGED; ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DEMOGRAPHY; DOUBLE BLIND PROCEDURE; DRUG EFFECT; FEMALE; GENOTYPE; HEART DEATH; HEART INFARCTION; HEART PROTECTION; HUMAN; MAJOR CLINICAL STUDY; MALE; NON INSULIN DEPENDENT DIABETES MELLITUS; OUTCOME ASSESSMENT; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; STROKE; VITAMIN SUPPLEMENTATION;

AGED; ANTIOXIDANTS; DIABETES MELLITUS, TYPE 2; DOUBLE-BLIND METHOD; FEMALE; GENETIC PREDISPOSITION TO DISEASE; GENOTYPE; HAPTOGLOBINS; HOMOZYGOTE; HUMANS; MALE; MIDDLE AGED; MYOCARDIAL INFARCTION; OXIDATIVE STRESS; PHARMACOGENETICS; PROSPECTIVE STUDIES; STROKE; TOCOPHEROLS;

EID: 38549138535     PISSN: 10795642     EISSN: None     Source Type: Journal    
DOI: 10.1161/ATVBAHA.107.153965     Document Type: Article

References (36)

1. Vivekananthan DP, Penn MS, Sapp SK, Hsu A, Topol EJ. Use of antioxidant vitamins for the prevention of cardiovascular disease: metaanalysis of randomized trials. Lancet. 2003;361:2017-2023.
2. HOPE and HOPE-TOO Trial Investigators. Effects of long-term vitamin E supplementation on cardiovascular events and cancer. JAMA. 2005;293:1338-1347.
3. The Heart Outcomes Prevention Evaluation (HOPE) Study Investigators. Vitamin E supplementation and cardiovascular events in high risk patients. N Engl J Med. 2000;342:154-160.
4. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20,536 high risk individuals; a randomized placebo controlled trial. Lancet. 2002;360:7-22.
5. Waters DD, Alderman EL, Hsia J, Howard BV, Cobb FR, Rogers WJ, Ouyang P, Thompson P, Tardif JC, Higginson L, Bittner V, Steffes M, Gordon DJ, Proschan M, Younes N, Verter JI. Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in post menopausal women: a randomized controlled trial. JAMA. 2002;288:2432-2440.
6. Collaborative Group of the Primary Prevention Project. Low dose aspirin and vitamin E in people at cardiovascular risk: a randomized trial in general practice. Lancet. 2001;357:89-95.
7. GISSI-Prevenzione Investigators. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Lancet. 1999;354:447-455.
8. Stephens NG, Parsons A, Schofeld PM, Kelly F, Cheeseman K, Mitchinson MJ. Randomized controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet. 1996;347:781-786.
9. Lee IM, Cook NR, Gaziano JM, Gordon D, Ridker PM, Manson JE, Hennekens CH, Buring JE. Vitamin E in the primary prevention of cardiovascular disease and cancer. The Women's Health Study: a randomized controlled trial. JAMA. 2005;294:56-65.
10. Brown BG, Crowley J. Is there any hope for vitamin E? JAMA. 2005;293:1387-1390.
11. Redberg RF. Vitamin E and Cardiovascular Health. JAMA. 2005;294:107-109.
12. Miller ER, Barriuso RP, Dalal D, Riemersma RA, Appel LJ, Guallar E. Meta-analysis: high dosage vitamin E supplementation may increase all cause mortality. Ann Intern Med. 2005;142:37-46.
13. Steinberg D, Witztum JL. Is the oxidative modification hypothesis relevant to human atherosclerosis? Do the antioxidant trials conducted to date refute the hypothesis? Circulation. 2002;105:2107-2111.
14. Levy AP. Application of pharmacogenomics in the prevention of diabetic cardiovascular disease: mechanistic basis and clinical evidence for utilization of the haptoglobin genotype in determining benefit from antioxidant therapy. Pharm Therapeutics. 2006;112:501-512.
15. Bowman BH, Kurosky A. Haptoglobin: the evolutionary product of duplication, unequal crossing over, and point mutation. Adv Hum Genet. 1982;12:189-261.
16. Frank M, Lache O, Enav B, Szafranek T, Levy NS, Ricklis RM, Levy AP. Structure/function analysis of the anti-oxidant properties of haptoglobin. Blood. 2001;98:3693-3698.
17. Asleh R, Marsh S, Shiltruck M, Binah O, Guetta J, Lejbkowicz F. Enav B, Shehadeh N, Kanter Y, Lache O, Cohen O, Levy NS, Levy AP Genetically determined heterogeneity in hemoglobin scavenging and susceptibility to diabetic cardiovascular disease. Circ Res. 2003;92:1193-1200.
18. Asleh R, Guetta J, Kalet-Litman S, Miller-Lotan R, Levy AP. Haptoglobin genotype and diabetes dependent differences in iron mediated oxidative stress in vitro and in vivo. Circ Res. 2005;96:435-441.
19. Levy AP, Purosothaman KR, Levy NS, Purosothaman M, Strauss M, Asleh R, Marsh S, Cohen O, Moestrup SK, Moller HJ, Zias EA, Benhayon D, Fuster V, Moreno PR. Downregulation of the hemoglobin scavenger receptor in individuals with diabetes and the Hp 2-2 genotype: implications for the response to intraplaque hemorrhage and plaque vulnerability. Circ Res. 2007;101:106-110.
20. Bamm VV, Tsemakhovich VA, Shaklai M, Shaklai N. Haptoglobin phenotypes differ in their ability to inhibit heme transfer from hemoglobin to LDL. Biochemistry. 2004;43:3899-3906.
21. Levy AP, Hochberg I, Jablonski K, Resnick H, Best L, Lee ET, Howard BH. Haptoglobin phenotype and the risk of cardiovascular disease in individuals with diabetes: The Strong Heart Study. J Am Coll Card. 2002;40:1984-1990.
22. Roguin A, Koch W, Kastrati A, Aronson D, Schomig A, Levy AP. Haptoglobin genotype is predictive of major adverse cardiac events in the one year period after PTCA in individuals with diabetes. Diab Care. 2003;26:2628-2631.
23. Suleiman M, Aronson D, Asleh R, Kapelovich MR, Roguin A, Meisel SR, Shochat M, Suleiman A, Reisner SA, Markiewicz W, Hammerman H, Lotan R, Levy NS, Levy AP. Haptoglobin polymorphism predicts 30-day mortality and heart failure in patients with diabetes and acute myocardial infarction. Diabetes. 2005;54:2802-2806.
24. Levy AP. Haptoglobin phenotype and diabetic cardiovascular disease. Israel Med Assoc J. 2004;6:308-310.
25. Levy AP, Gerstein H, Lotan R, Ratner R, McQueen M, Lonn E, Pogue J. The effect of vitamin E supplementation on cardiovascular risk in diabetic individuals with different haptoglobin phenotypes. Diab Care. 2004;27:2767.
26. Hochberg I, Roguin A, Nikolsky E, Chanderashekhar PV, Cohen S, Levy AP. Haptoglobin phenotype and coronary artery collaterals in diabetic patients. Atherosclerosis. 2002;161:441-446.
27. Koch W, Latz W, Eichinger M, Roguin A, Levy AP, Schomig A, Kastrati A. Genotyping of common haptoglobin polymorphism Hp1/2 based on the polymerase chain reaction. Clin Chem. 2002;48:1377-1382.
28. Blum S, Asaf R, Guetta J, Miller-Lotan R, Asleh R, Kremer R, Levy NS, Berger FG, Fu X, Zhang R, Hazen SL, Levy AP. Haptoglobin genotype determines myocardial infarct size in diabetic mice. J Am Coll Card. 2007;49:82-87.
29. Levy AP, Levy JE, Kalet-Litman, Miller-Lotan R, Levy NS, Asaf R, Guetta J, Yang C, Purushothaman KR, Fuster V, Moreno PR. Haptoglobin genotype is a determinant of iron, lipid peroxidation and macrophage accumulation in the atherosclerotic plaque. Arterioscler Thromb Vasc Biol. 2007;27:134-140.
30. Asleh R, Miller-Lotan R, Aviram M, Hayek T, Yulish M, Levy JE, Miller B, Blum S, Milman U, Shapira C, Levy AP. Haptoglobin genotype is a regulator of reverse cholesterol transport in diabetes in vitro and in vivo. Circ Res. 2006;99:1419-1425.
31. Sadrzadeh SMH, Graf E, Panter SS, Hallaway PE, Eaton JW. Hemoglobin-a biologic Fenton reagent. J Biol Chem. 1984;259:14354-14356.
32. Levy AP, Moreno PR. Intraplaque hemorrhage. Curr Mol Med. 2006;6:479-488.
33. Boaz M, Smetana S, Weinstein T, Matas Z, Gafter U, Iaina A, Knecht A, Weissgarten Y, Brunner D, Fainaru M, Green MS. Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease (SPACE): randomized placebo controlled trial. Lancet. 2000;356:1213-1218.
34. Lee DH, Liu DY, Jacobs DR, Shin HR, Song K, Lee IK, Kim B, Hider RC. Common presence of non-transferrin bound iron among patients with type 2 diabetes. Diab Care. 2006;29:1090-1095.
35. Lee DH, Folsom AR, Harnack L, Halliwell B, Jacobs DR. Does supplemental vitamin C increase cardiovascular disease risk in women with diabetes? Am J Clin Nutr. 2004;80:1194-1200.
36. Levy AP, Friedenberg P, Lotan R, Ouyang P, Triputti M, Higginson L, Cobb FR, Tardif JC, Bittner V, Howard BV. The effect of vitamin therapy on the progression of coronary artery atherosclerosis varies by haptoglobin type in post-menopausal women. Diab Care. 2004;27:925-930.