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The very steep dose gradients that confer brachytherapy its tumoricidal advantage also pose a double-edged risk: minimal misalignment or anatomical variation can result in unintended irradiation of surrounding healthy tissue, leading to acute and late toxicities [101, 102]

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Indeed, the European multicenter study coordinated by Graham reports that, whereas basal hyperhomocysteinemia only shows an additive effect with hypercholesterolemia, it has a synergistic effect with both hypertension and smoking on the incidence of atherosclerotic vascular disease (Graham et al, 1997)