Subclinical disease measures have thus enhanced studies of CVD risk by examining the early stages of CVD in an objective manner free of biases related to severity, diagnostic suspicion, or completeness of medical investigation. Because subclinical disease is asymptomatic and previously unknown to participants, it is unlikely to have any direct impact on health behavior, such as lifestyle modification or medication use, which may limit the detection of risk relationships with clinical disease. In addition, the continuous nature of most subclinical measures greatly increases power to detect risk associations compared to discrete measures, such as presence or absence of clinical events. Most importantly, subclinical measures now permit the epidemiologic investigation of CVD risk to focus on the biology of CVD rather than on vagaries in its diagnosis. Application of non-invasive measures in ongoing prospective, population-based studies has demonstrated a surprisingly high prevalence of subclinical disease. Atherosclerotic plaque is extremely common in the extracranial carotid arteries of United States men and women older than 45 years and can be detected in subjects at low risk as defined by traditional risk factors. Coronary calcium, a specific marker for coronary atherosclerosis, is present in 10 percent of women and 30 percent of men aged 30-39 and increases in prevalence with age. One-sixth of men and nearly one-fifth of women in Framingham have echocardiographically defined left ventricular hypertrophy, and over 30 percent of persons over age 65 in CHS have MRI-defined cerebral infarcts.