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

Andrew P. Levy, Paula Friedenberg, Rachel Lotan, Pamela Ouyang, Mark Tripputi, Lyall Higginson, Frederick R. Cobb, Jean Claude Tardif, Vera Bittner, Barbara V. Howard

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)925-930
Number of pages6
JournalDiabetes Care
Volume27
Issue number4
DOIs
StatePublished - Apr 2004

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Haptoglobins
Vitamins
Atherosclerosis
Arteries
Therapeutics
Angiography
Estrogens
Antioxidants
Alleles
Estrogen Replacement Therapy
Coronary Stenosis
Hormone Replacement Therapy
Homozygote
Vitamin E
Ascorbic Acid
Coronary Artery Disease
Research Design
Cardiovascular Diseases
Placebos
Prospective Studies

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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The Effect of Vitamin Therapy on the Progression of Corona Artery Atherosclerosis Varies by Haptoglobin Type in Postmenopausal Women. / Levy, Andrew P.; Friedenberg, Paula; Lotan, Rachel; Ouyang, Pamela; Tripputi, Mark; Higginson, Lyall; Cobb, Frederick R.; Tardif, Jean Claude; Bittner, Vera; Howard, Barbara V.

In: Diabetes Care, Vol. 27, No. 4, 04.2004, p. 925-930.

Research output: Contribution to journalArticle

Levy, AP, Friedenberg, P, Lotan, R, Ouyang, P, Tripputi, M, Higginson, L, Cobb, FR, Tardif, JC, Bittner, V & Howard, BV 2004, 'The Effect of Vitamin Therapy on the Progression of Corona Artery Atherosclerosis Varies by Haptoglobin Type in Postmenopausal Women', Diabetes Care, vol. 27, no. 4, pp. 925-930. https://doi.org/10.2337/diacare.27.4.925
Levy, Andrew P. ; Friedenberg, Paula ; Lotan, Rachel ; Ouyang, Pamela ; Tripputi, Mark ; Higginson, Lyall ; Cobb, Frederick R. ; Tardif, Jean Claude ; Bittner, Vera ; Howard, Barbara V. / The Effect of Vitamin Therapy on the Progression of Corona Artery Atherosclerosis Varies by Haptoglobin Type in Postmenopausal Women. In: Diabetes Care. 2004 ; Vol. 27, No. 4. pp. 925-930.
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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.",
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AU - Ouyang, Pamela

AU - Tripputi, Mark

AU - Higginson, Lyall

AU - Cobb, Frederick R.

AU - Tardif, Jean Claude

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AU - Howard, Barbara V.

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N2 - 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.

AB - 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.

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