"Cardiovascular disease currently is the primary cause of death of two million people in Europe each year. Early cardiovascular disease can be treated effectively and at ever-lower costs. This has raised hopes that if large groups of individuals who are at an increased risk could be identified earlier, morbidity and mortality from the disease could potentially be reduced. New risk questionnaires, biomarkers and computed tomography imaging technology (CT) have identified undiagnosed increased risks in asymptomatic people. However, it is unknown whether such screening for subclinical disease improves outcomes enough to justify the associated adverse effects and costs of the new strategies.Benefits are only to be expected if large groups of asymptomatic people can be reached. Moreover, evidence can only be shown unambiguously in randomised controlled trials (RCTs). We therefore propose a large-scale population-based screening trial, in which we will invite 330,800 men and women (from population-based registries) to measure their waist circumference and fill out a risk questionnaire. 39,000 persons at elevated risk will then be randomised to either: a) no testing, b) be screened using the classic tests (lipids, glucose, blood pressure) or c) be screened using a CT scan of the coronary arteries. The first objective of the trial is to establish whether inviting (and subsequently selecting high-risk) asymptomatic men and women for a ‘classic’ risk factor assessment, followed by early and intensive medical intervention in subjects at increased risk, will decrease coronary heart disease (CHD) mortality and morbidity by 15% or more within five years. The second objective is to establish whether the coronary calcium score using CT will improve outcomes with another 15% for asymptomatic persons. The third objective is to model the natural history of atherosclerotic plaques and CHD risk, to estimate effects, adverse effects and costs, and to guide public health policies."