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

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'sAngiographic 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 Ϯ 0.040 mm, P ϭ 0.049). This benefit was more marked in diabetic subjects (0.149 Ϯ 0.064 mm, P ϭ 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 Ϯ 0.057 mm, P ϭ 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.

The Medicinal Value and the Numerous Sources of Vitamin C - A Review

“…63 In a study by Osganian et al, 64 intake of VC in the dose of 400mg/day or more was observed to reduce the fatal and nonfatal coronary heart disease in diabetics. Levy et al, 65 studied intake of vitamins and their impact on the progression of coronary artery atherosclerosis and the results presented that vitamin supplementation was related with improvement in coronary artherosclerosis in diabetic females having two copies of haptoglobin 1 gene whereas the condition worsened in diabetic females having two copies of haptoglobin 2 gene thus claiming that genetic factors of the individual also play a primary role. In an experiment effect of VC on diabetes induced endothelial dysfunction and generation of reactive oxygen species was examined.…”

Role of ascorbic acid and tocopherol in the prevention and treatment of diseases from the standpoint of evidence-based medicine

“…Таким образом, результаты обобщенного анализа проспек-тивных когортных исследований, а также отдельных, крупных проспективных исследований, таких, как эпидемиологическое исследование NHANES I [8,9] и NHS [10], анализ результатов фармакокинетических исследований перорального приема вита-мина С у человека, показывают, что максимальное снижение ри-ска развития ИБС происходит при употреблении витамина С в дозе более 400 мг/сут [7].…”

“…Результаты одного рандомизированного контролируемого исследования пересмо-трены с учетом генотипирования пациентов по гаптоглобину. Выявлено, что антиоксидантная терапия (1000 мг/сут витамина C + 800 МЕ/сут витамина Е) ассоциируется с регрессом коронар-ного атеросклероза у женщин с СД с двумя копиями гена гапто-глобина-1, при этом наблюдалось прогрессирование коронарно-го атеросклероза у пациентов с двумя копиями гена гаптоглоби-на-2 [9]. Значение этих результатов не изучено, но они предпо-лагают, что могут существовать группы людей с СД, которым полезна антиоксидантная терапия, при этом другим субпопуля-циям может быть причинен вред.…”

ELISA for Determination of the Haptoglobin Phenotype

“…However, there is considerable geographic and ethnic variation in the distribution of haptoglobin phenotypes (1 ). Over the past 3-4 years our laboratory has demonstrated that haptoglobin is a major susceptibility gene for the development of diabetic vascular complications in multiple longitudinal and cross-sectional population studies (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). Diabetic individuals homozygous for the haptoglobin 2 allele were shown to be at five times greater risk of developing cardiovascular disease compared with diabetic individuals homozygous for the haptoglobin 1 allele, with an intermediate risk for the heterozygote (8 ).…”