The Effect of Vitamin Therapy on the Progression of Coronary Artery Atherosclerosis Varies by Haptoglobin Type in Postmenopausal Women

  1. Andrew P. Levy, MD, PHD1,
  2. Paula Friedenberg, MS2,
  3. Rachel Lotan, PHD1,
  4. Pamela Ouyang, MD3,
  5. Mark Tripputi, MS2,
  6. Lyall Higginson, MD4,
  7. Frederick R. Cobb, MD5,
  8. Jean-Claude Tardif, MD6,
  9. Vera Bittner, MD7 and
  10. Barbara V. Howard, PHD8
  1. 1Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
  2. 2George Washington University Biostatistics Center, Washington, DC
  3. 3Division of Cardiology, Johns Hopkins Bayview Medical Center, Baltimore, Maryland
  4. 4University of Ottawa Heart Institute, Ottawa, Ontario, Canada
  5. 5Duke Center for Living, Duke University, Durham, North Carolina
  6. 6Montreal Heart Institute, Montreal, Quebec, Canada
  7. 7Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, Alabama
  8. 8Department of Cardiology, Medstar Research Institute, Washington, DC
  1. Address correspondence and reprint requests to Dr. Andrew P. Levy, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. E-mail: alevy{at}tx.technion.ac.il

Abstract

OBJECTIVE—Antioxidant trials have not demonstrated efficacy in slowing cardiovascular disease but could not rule out benefit for specific patient subgroups. Antioxidant therapy reduces LDL oxidizability in haptoglobin 1 allele homozygotes (Hp 1-1), but not in individuals with the haptoglobin 2 allele (Hp 2-1 or Hp 2-2). We therefore hypothesized that haptoglobin type would be predictive of the effect of vitamin therapy on coronary atherosclerosis as assessed by angiography.

RESEARCH DESIGN AND METHODS—We tested this hypothesis in the Women’s Angiographic Vitamin and Estrogen (WAVE) trial, a prospective angiographic study of vitamins C and E with or without hormone replacement therapy (HRT) in postmenopausal women. Haptoglobin type was determined in 299 women who underwent baseline and follow-up angiography. The annualized change in the minimum luminal diameter (MLD) was examined in analyses stratified by vitamin use, haptoglobin type, and diabetes status.

RESULTS—We found a significant benefit on the change in MLD with vitamin therapy as compared with placebo in Hp 1-1 subjects (0.079 ± 0.040 mm, P = 0.049). This benefit was more marked in diabetic subjects (0.149 ± 0.064 mm, P = 0.021). On the other hand, there was a trend toward a more rapid decrease in MLD with vitamin therapy in Hp 2-2 subjects, which was more marked in diabetic subjects (0.128 ± 0.057 mm, P = 0.027). HRT had no effect on these outcomes.

CONCLUSIONS—The relative benefit or harm of vitamin therapy on the progression of coronary artery stenoses in women in the WAVE study was dependent on haptoglobin type. This influence of haptoglobin type seemed to be stronger in women with diabetes.

Footnotes

  • A.P.L. is the author of a patent that claims to predict diabetic vascular complications based on the haptoglobin phenotype. He has received no financial compensation from this patent.

    • Accepted January 6, 2004.
    • Received November 3, 2003.
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  1. doi: 10.2337/diacare.27.4.925 Diabetes Care April 2004 vol. 27 no. 4 925-930
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