Kentucky is part of the Coronary Valley, which comprises ten states along the Ohio and Mississippi Rivers that rank among those with the highest incidence of heart disease in the United States. Kentucky consistently ranks near the highest in the nation, and within the state, the incidence is markedly higher in the eastern, Appalachian region. In a study of heart disease risk factors among residents of Clay County, which is located in this region, woe found, surprisingly, that the prevalence of elevated plasma cholesterol is slightly lower than in the United States overall. However, we noted a higher incidence of other traditional risk factors, including hypertension, cigarette smoking, obesity, and physical inactivity in this county, as well as a greater frequency of metabolic syndrome (MS) components. These findings may explain the high prevalence of cardiovascular (CV) disease in general and coronary heart disease (CHD) in particular, in parts of rural Appalachia even without the presence of significantly elevated cholesterol levels.