To further the study of the relationship between risk factors and atherosclerosis and to avoid the biases involved in relying solely on clinical disease outcomes, objective and unbiased measures of cardiovascular disease (CVD) have been introduced in NHLBI-initiated epidemiologic studies of CVD etiology. Two well-developed examples include echocardiography and carotid ultrasound. The observation that risk of subsequent cardiovascular events and mortality increased 1.5 to 2-fold per 50 gm/m of echocardiographically-defined left ventricular mass in Framingham led to inclusion of echocardiographic LV mass assessment in several population samples. Development and validation of duplex ultrasound imaging as a measure of atherosclerosis provided for the first time a method for visualizing the atherosclerotic process at the level of the vessel wall and suitable for application in population-based studies.