Previous studies had demonstrated high prevalences of coronary disease risk factors and occult coronary disease in this sibling population. Subjects were recruited to come for a one day screening, with measurement of coronary disease risk factors (blood pressure, smoking, lipid profile, apolipoproteins B and A1, lipoprotein(a), blood glucose, insulin, and fibrinogen), and a maximal treadmill test with tomographic thallium imaging to identify occult coronary disease. Platelet function was assessed by spontaneous in-vitro aggregation, activated IIa/IIIb receptor density, and serum thromboxane B2 concentration. Factors contributing to sudden cardiac death were assessed by an echocardiogram for left ventricular mass, electrocardiogram (ECG) for QRS late potentials, and 24 hour ECG monitoring for ventricular arrhythmias, episodes of silent ischemia, and heart rate variability (to assess adrenergic drive). Vascular reactivity was characterized by heart rate and blood pressure changes during Stroop color card and cold pressor testing. Siblings with an abnormal exercise ECG and/or thallium scan were offered coronary arteriography to assess the severity of angiographic coronary disease and the vasomotor responses to isometric handgrip and intracoronary acetylcholine, an endothelium-dependent vasodilator. In coronary arteries with minimal angiographic disease, changes in coronary vascular resistance during handgrip and acetylcholine were also measured with a doppler flow velocity catheter and the proximal arteries were imaged with intravascular ultrasound.