Effect of Vitamins C and E on Vascular Reactivity—Reply

In Reply.—Dr Kaufman questions the clinical significance of our observation that a high-fat meal transiently reduces endothelial function as measured by flow-mediated vasoactivity and that pretreatment with antioxidant vitamins C and E blunts this effect. The objection appears to be based on the fact that the observed alterations in vasoactivity are similar to the precision of the ultrasound technique used. The simple answer is that such observations reach statistical significance if adequately sized groups are studied. For example, 21 of 22 reported trials of cholesterol lowering have found reductions in the progression of coronary or carotid atherosclerosis of less than 1% per year, far less than the precision of quantitative coronary arteriography (about 10%).^1- 2 Many of these studies are highly statistically significant. Whether such studies are clinically significant is not a statistical issue. In the case of cholesterol lowering, 5 large randomized trials have now shown 24% to 36% reductions in major cardiovascular events.³ This clinical significance was predicted, but not proven, by the mechanistic angiographic trials. In our case, 2 recent articles have confirmed that short-term fat intake impairs endothelial function and increases blood coagulability.^4- 5 The observed magnitude of changes in the intermediate biological outcomes studied was similar to our findings. The clinical significance of these findings on the vascular biology of fat and antioxidant vitamin intake awaits clinical trials with appropriate end points generated from these statistically significant and interesting observations.