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Sir,—As Meyers et al note, data regarding the iron hypothesis of atherogenesis are inconsistent,1 and data regarding the closely allied oxidation hypothesis are also conflicting.2 Thus, I suggest that the beneficial effect of blood donation on cardiovascular disease is caused by a reduction in haematocrit and blood viscosity. Haematocrit was shown to be a risk factor for atherosclerosis in the Framingham study.3 Haematocrit is also a very powerful determinant of blood viscosity.4 Increased blood viscosity is thought to accelerate atherogenesis by perpetuating areas of low shear in the vascular tree, prolonging the residence time of atherogenic particles, such as platelets and lipoproteins, on the endothelium.5 This prolonged residence time would facilitate microthrombus formation and lipoprotein diffusion. A decrease in blood viscosity, as well as reducing residence time, would increase the shear dependent expression of atheroprotective molecules such as nitric oxide and prostacyclin.6 The decreased expression of these molecules in atherosclerosis is usually ascribed to a putative endothelial dysfunction caused by the cytotoxic effects of oxidised low density lipoprotein (LDL).
LDL increases blood viscosity, presumably by fostering erythrocyte aggregation.4 Thus, the decrease in blood viscosity associated with blood donation might be most pronounced in individuals with the highest serum LDL. This is consistent with the observation of Meyers et al, who noted that the benefit of blood donation was greatest in males with the highest serum LDL.1
Atherosclerosis is a non-specific condition affecting nearly everyone in industrialised societies, not simply those with hypercholesterolaemia. In my view, theories of atherogenesis that focus on lipids and do not adequately explain the accelerated atherogenesis associated with other risk factors, such as increased haematocrit, hypertension, hyperfibrinogenaemia, and raised plasma viscosity, are unlikely to be correct. Increased blood viscosity is found in association with each of these risk factors.5 ThePrinciple of Simplicity (Ockham’s Razor), which holds that the simplest theory that explains all possible cases is most likely to be correct, suggests to me that a non-specific effector such as blood viscosity must play a more central role in atherogenesis than accumulation of cholesterol in the vessel wall.