Dual therapy with statins and antioxidants is superior to statins alone in decreasing the risk of cardiovascular disease in a subgroup of middle-aged individuals with both diabetes mellitus and the haptoglobin 2-2 genotype

Arteriosclerosis, Thrombosis, and Vascular Biology

Volumn 28, Issue 3, 2008, Pages

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

^a TECHNION ISRAEL INSTITUTE OF TECHNOLOGY   (Israel)

^b CLALIT HEALTH SERVICES   (Israel)

^c RAMBAM MEDICAL CENTER   (Israel)

^d PharmaBrains Israel   (Israel)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA TOCOPHEROL; ANTIOXIDANT; HAPTOGLOBIN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; PLACEBO;

ADULT; AGED; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; GENOTYPE; HEART DEATH; HEART INFARCTION; HEART PROTECTION; HUMAN; LETTER; MAJOR CLINICAL STUDY; MIDDLE AGED; NON INSULIN DEPENDENT DIABETES MELLITUS; OXIDATIVE STRESS; PHARMACOGENETICS; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RISK REDUCTION; STROKE; VITAMIN SUPPLEMENTATION; AGE; DRUG COMBINATION; FEMALE; GENETIC MARKER; GENETICS; INCIDENCE; MALE; METABOLISM; MULTICENTER STUDY; PROGNOSIS; REFERENCE VALUE; RISK ASSESSMENT; SEX DIFFERENCE; SURVIVAL RATE; TREATMENT OUTCOME;

AGE FACTORS; AGED; ANTIOXIDANTS; CARDIOVASCULAR DISEASES; DIABETES MELLITUS, TYPE 2; DRUG THERAPY, COMBINATION; FEMALE; GENETIC MARKERS; GENOTYPE; HAPTOGLOBINS; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; INCIDENCE; MALE; MIDDLE AGED; PROGNOSIS; REFERENCE VALUES; RISK ASSESSMENT; SEX FACTORS; SURVIVAL RATE; TREATMENT OUTCOME; VITAMIN E;

EID: 40749088915     PISSN: 10795642     EISSN: None     Source Type: Journal    
DOI: 10.1161/ATVBAHA.107.159905     Document Type: Letter

References (24)

1. Ceriello, PA. Oxidative stress and diabetes associated complications. Endo Prac. 2006;12:60-62.
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. 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.
13. 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. Pharmacology and Therapeutics. 2006;112:501-512.
14. Bowman BH, Kurosky A. Haptoglobin: the evolutionary product of duplication, unequal crossing over, and point mutation. Adv Hum Genet. 1982;12:189-261.
15. Langlois MR, Delanghe JR. Biological and clinical significance of haptoglobin polymorphism in humans. Clin Chem. 1996;42:1589-1600.
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. Miller YI, Altamentova SM, Shaklai N. Oxidation of low density lipoprotein by hemoglobin stems from a heme initiated globin radical: antioxidant role of haptoglobin. Biochemistry. 1997;36:12189-12198.
18. 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.
19. Levy AP, Hochberg I, Jablonski K, Resnick H, Best L, Lee ET, Howard BV. Haptoglobin phenotype and the risk of cardiovascular disease in individuals with diabetes: The Strong Heart Study. J Am Coll Card. 2002;40:1984-1990.
20. 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. Diabetes Care. 2003;26:2628-2631.
21. 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;19:2802-2806.
22. Milman U, Blum S, Shapira C, Aronson D, Miller-Lotan R, Anbinder Y, Alsheik J, Bennett L, Kostenko M, Landau M, Keidar S, Levy Y, Khemlin A, Radan A, Levy AP: Milman U, Blum S, Shapira C, Aronson D, Miller-Lotan R, Anbinder Y, Alsheik J, Bennett L, Kostenko M, Landau M, Keidar S, Levy Y, Khemlin A, Radan A, Levy AP. 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. Arterioscler Thromb Vasc Biol. 2008;28:341-347.
23. Brown BG, Zhao XQ, Chait A, Fisher LD, Cheung MC, Morse JS, Dowdy AA, Marino EK, Bolson EL, Alaupovic P, Frohlich J, Albers JJ. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med. 2001;345:1583-1592.
24. Brown BG, Cheung MC, Lee AC, Zhao XQ, Chait A. Antioxidant vitamins and lipid therapy: end of a long romance? Art Thromb Vasc Biol. 2002;22:1535-1546.