A positive exercise electrocardiogram (ECG) is not infrequent occurrence in asymptomatic hypercholesterolemic patients, but the number of false-positive tests may be relatively high (50%). Therefore, the ability of a positive stress ECG to predict coronary artery lesions is low even in populations with > or =1 cardiovascular risk factors. To increase the diagnostic value of exercise tests for screening asymptomatic individuals, we analyzed whether combined clinical parameters with carotid echography would accurately predict coronary atherosclerotic lesions by coronary angiography in asymptomatic hypercholesterolemic patients with a positive exercise ECG. Seventy-six asymptomatic patients (between 35 and 65 years of age) with hypercholesterolemia (total plasma cholesterol >6.5 mmol/L or 250 mg/dl) and a positive stress ECG were referred for carotid B-mode echography and coronary angiography. Carotid echography data were divided into 2 categories: (1) absence of any atherosclerotic plaque, or (2) presence of > or =1 arterial plaques. Coronary stenosis assessed by coronary angiography was considered to correspond to a > or =50% reduction of coronary lumen diameter. Forty-three patients (57%) displayed coronary lesions; most (38; 88%) had carotid plaque. Multivariate analysis showed that the presence of carotid plaque was significantly associated with coronary stenosis (odds ratio 15.2; confidence interval 5.0 to 54.5). In subgroups characterized by high frequency of false-positive exercise electrocardiographic tests (women and patients with a 10-year predicted risk of coronary artery disease [CAD] <15%), none of the patients without carotid plaque exhibited coronary lesions. Echographic evaluation of carotid plaque (plaque vs no plaque) significantly improved the diagnostic specificity of exercise electrocardiography. We conclude that the combination of clinical, electrical, and echographic data facilitates cost-effective noninvasive detection of CAD in asymptomatic hypercholesterolemic patients.