The effect of vitamin therapy on the progression of coronary artery atherosclerosis varies by haptoglobin type in postmenopausal women.
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.


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.
Levy
Andrew P
AP
Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. alevy@tx.technion.ac.il
Friedenberg
Paula
P
Lotan
Rachel
R
Ouyang
Pamela
P
Tripputi
Mark
M
Higginson
Lyall
L
Cobb
Frederick R
FR
Tardif
Jean-Claude
JC
Bittner
Vera
V
Howard
Barbara V
BV
D000368:Aged; D000975:Antioxidants / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000627:therapeutic use*; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood* / Q000000981:diagnostic imaging / Q000188:drug therapy*; D003331:Coronary Vessels / Q000187:drug effects; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006242:Haptoglobins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D017698:Postmenopause / Q000097:blood; D011446:Prospective Studies; D014810:Vitamin E / Q000627:therapeutic use*
D000975:Antioxidants; D006242:Haptoglobins; D008055:Lipids; D014810:Vitamin E; D001205:Ascorbic Acid