Slide 16 of 16

13. In all epidemiologic studies, the question of potential confounding must be considered. In the present situation of valve disorders with appetite suppressant use, an important potential confounder may be obesity itself. Could the high prevalence of significant valvular regurgitation observed in these studies be due to obesity rather than exposure to fenfluramine or dexfenfluramine, with or without phentermine? From each survey site, and from the observational epidemiologic study, 48 echocardiograms were identified as having been performed in patients prior to or at the start of treatment with an appetite suppressant. None (0/48) met the research case definition. These results suggest that the background rate of valvular regurgitation in obese individuals is probably no higher than in non-obese individuals. In support of this, CARDIA found an inverse association between body weight and prevalence of regurgitant valvular lesions. At the time of these analyses, covariate data were not available from most sites. It is important to note that these data are based on prevalent rather than incident cases.