M.Sc.(Med.), Faculty of Health Sciences, University of the Witwatersrand, 2009. / Leptin is a substance that is released from adipose tissue and although it is primarily employed to modify body size, it also targets a number of other tissues, including the myocardium. Although plasma leptin concentrations may predict cardiovascular risk beyond conventional measurements, it is uncertain whether this may be explained by an independent effect on left ventricular mass (LVM) and geometry. Previous clinical studies evaluating the independent relationship between plasma leptin concentrations and LVM have been conducted in either small study samples (n=31-55), in severely obese participants only, in select subgroups (with insulin resistance) or in population samples with a relatively low mean body mass index (BMI). In the present dissertation I therefore assessed whether plasma leptin concentrations are associated with LVM and LV mean wall thickness independent of adiposity indices in 378 adults of African descent randomly recruited from a population sample with ~63% of people whom were either overweight or obese. LVM was determined using two-dimensional directed M-mode echocardiography and indexed to height2.7 (LVMI). ~28% of the sample had LV hypertrophy. Marked differences in plasma leptin concentrations were noted between men and women. Thus, multivariate regression analysis was employed to identify independent relations between plasma leptin concentrations and either LVMI or LV mean wall thickness in sex-specific groups. Before adjustments for potential confounders, plasma leptin concentrations were associated with LVMI in both women (r=0.25, p<0.0001) and in men (r=0.20, p=0.017) as well as with LV mean wall thickness in both women (r=0.22, p<0.001) and in men (r=0.27, p=0.002). Moreover, participants with LV hypertrophy defined as an LVM index of >51 g/m2 had markedly greater plasma leptin concentrations than those participants without LV hypertrophy. However, plasma leptin concentrations were also associated with age, conventional systolic blood pressure and with adiposity indices (p<0.0001), factors that had robust relationships with LVMI and LV mean wall thickness. In multivariate regression models with plasma leptin concentrations, adiposity indices, age, systolic blood pressure and a number of alternative potential confounders in the same regression model, although adiposity indices were strong independent predictors of both LVMI and LV mean wall thickness in both women and men (p<0.002-p<0.0001), plasma leptin concentrations were not independently related to either LVMI (p=0.32-0.96), or LV mean wall thickness (p=0.33-0.81). In conclusion, plasma leptin concentrations, although associated with, are not independent predictors of LVMI beyond adiposity indices and other related factors in a population sample with a high prevalence of excess adiposity. Therefore, plasma leptin concentrations are unlikely to predict cardiovascular risk beyond conventional risk measurements because of an impact on LVM.