Modifying Oxidative Damage in WAVE - Ancillary to WAVE
Condition: Cardiovascular Diseases; Coronary Disease; Heart Diseases
MeSH terms: Cardiovascular Diseases; Heart Diseases; Coronary Disease
Study type: Observational

Summary: 
      To determine the effects of four treatments (placebo, a vitamin E and C regimen, a hormone
      replacement regimen, and a combined vitamin/hormone replacement regimen) on specific markers
      of oxidative damage in coronary arteries of postmenopausal women.
    

Detailed description: 
      BACKGROUND:

      Supplemental vitamin E has been associated with a reduced risk of recurrent myocardial
      infarctions, with efficacy related to dosage and the duration of treatment. Its effects may
      be enhanced by vitamin C, an antioxidant that can regenerate vitamin E activity.
      Theoretically vitamin E and C (VitE/C) accumulate in the vascular wall with a concurrent
      reduction in oxidative damage, a primary feature of atherosclerotic lesions. Estrogen/hormone
      replacement therapy (HRT) also may reduce oxidative damage, and it may enhance the effect of
      vitamin E and C. These hypotheses are supported by studies defining oxidation-dependent
      accumulation of lipids in developing atherosclerosis; the detection of oxidative damage
      products, such as oxidized-LDL particles, in human atherosclerotic lesions; and clinical
      studies associating antioxidant or estrogen supplementation with reductions in oxidative
      damage cardiovascular disease. Nevertheless, no human studies have evaluated the effect of
      long-term VitE/C treatment, which has been reported as being the most effective prevention
      factor by epidemiologic studies, on specific. biochemical markers of oxidative damage and
      concurrently their association with recurrent cardiovascular disease. In addition, no studies
      have characterized the effect of long-term HRT on markers of oxidative damage or HRT's
      potential synergistic effect with VitE/C therapy.

      DESIGN NARRATIVE:

      The study assayed specific biochemical measures of oxidative damage (all markers at closeout
      and nitrotyrosine and chlorotyrosine also at baseline) in the Women's Angiographic Vitamin
      and Estrogen (WAVE) Trial, which randomized 420 38-86 year old women with a prior
      cardiovascular disease event to placebo, Vitamin E/C, hormone replacement therapy (HRT) or
      the combination of VitE/C and HRT. WAVE determined the efficacy of these treatments on
      quantitative angiographic evaluation of minimal coronary artery diameter performed at
      baseline and at the final visit to be completed during the first 10 months of 2001. The
      ancillary study measured oxidation products from several classes of compounds (lipids by
      F2-isoprostanes, proteins by nitrotyrosine and chlorotyrosine, and DNA by
      8-hydroxy-2'-deoxyguanosine), thereby studying several major pathways that may lead to
      atherogenesis. In addition, inflammation with C-reactive protein, platelet activation with
      p-selectin, altered lipid metabolism with a lipid profile and other characteristics of the
      study population were integrated into the assessment of oxidative damage in WAVE. By
      measuring these various factors and by assessing oxidative damage in several classes of
      compounds, the authors tested the relationships among specific pathways of oxidative damage,
      supplemental VitE/C and/or HRT and other risk factors upon the progression of established
      macrovascular disease.
    

Time perspective: Retrospective