Ongoing controversies surrounding the vascular benefits of blood donation.

Benefits of Blood Donation It was with interest that we read the article by Ascherio and colleagues1 on blood donation and risk of coronary heart disease in the Health Professionals Follow-up Study. The authors convincingly demonstrated that a lifetime history of blood donation is not a risk predictor of symptomatic coronary heart disease in men aged 46 to 81 years. Their conclusion, however, that these results conflict with the hypothesis that iron depletion offers protection against cardiovascular disease (iron hypothesis2–4) requires caution. The Health Professionals Follow-up Study was not primarily designed to analyze the effects of iron stores on vascular risk. The information on blood donation collected in this study was the overall (lifetime) frequency. According to the iron hypothesis, however, only subjects who regularly donated blood at the beginning of the study period (1992) or preferably throughout the entire follow-up period can be expected to enjoy adequate protection against myocardial infarction, whereas the long-term beneficial effects of blood donation performed years to decades before the study period should be modest or even absent. In this context, it is worth mentioning that substantial iron accumulation occurs in women within a few years after menopause4,5 and an analogous condition may be found in men after discontinuation of regular blood donation. The data presented (assessment period and frequency of blood donation) lead us to estimate that less than one-fifth of all blood donors in this study were still active on entering the follow-up period. The proportion of active blood donors among subjects with incident coronary heart disease and those without is probably not the same. The risk of myocardial infarction increases with advancing age while the probability of blood donors still being active markedly decreases, especially beyond 60 years. A lower rate of active donors among subjects with coronary heart disease, however, may bias actual relations between iron depletion and vascular risk toward zero. Even among active donors, the probability of a positive influence on cardiovascular risk strongly depends on the efficacy of iron depletion. Because lifetime frequency of blood donation was low in this population (#4 times in 50% of donors1), the lowering of iron stores may often not be sufficient in extent or duration for cardiovascular benefits to emerge. In summary, when intending to test the iron hypothesis, the putatively small group of still-active blood donors with a prominent and long-lasting depletion of iron stores constitutes the actual target population to be compared with all others or with nondonors regarding vascular risk. Unfortunately, however, these subjects cannot be identified in the study by Ascherio and coworkers1 because of the lack of valid laboratory measures of body iron and, as a consequence, they are analyzed in concert with all other current and past donors. Spot measurements of ferritin in a 0.3% subsample 6 years before the actual study period are definitely not a substitute for serial measurements of ferritin in the entire population. Stefan Kiechl, MD Johann Willeit, MD Department of Neurology University Clinic Innsbruck Anichstr 35 A-6020 Innsbruck, Austria