Lung cancer, chronic obstructive pulmonary disease, and cardiovascular disease are highly prevalent in the general population and expected to cause most deaths by 2050. For these "Big-3," treatment might cure, delay, or stop the progression of disease at a very early stage. Lung nodule growth rate (a biomarker for lung cancer), emphysema/air trapping (a biomarker for chronic obstructive pulmonary disease), and coronary artery calcification (a biomarker for cardiovascular disease) are imaging biomarkers of early stages of the Big-3 that can be acquired with low-dose computed tomography (CT). We hypothesize that a (combined) lowdose CT examination for detection of all 3 diseases may significantly improve the cost-effectiveness of screening in the future. We review the current evidence of the imaging biomarkers for the detection of the Big-3 diseases and present the potential health economic potential of Big-3 screening. Furthermore, we review the low-dose CT protocols to acquire these biomarkers and describe the technical considerations when combining the CT protocols for the different biomarkers.

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Lung cancer, chronic obstructive pulmonary disease (COPD), and coronary artery disease (CAD) are expected to cause most deaths by 2050. State-of-the-art computed tomography (CT) allows early detection of lung cancer and simultaneous evaluation of imaging biomarkers for the early stages of COPD, based on pulmonary density and bronchial wall thickness, and of CAD, based on the coronary artery calcium score (CACS), at low radiation dose. To determine cutoff values for positive tests for elevated risk and presence of disease is one of the major tasks before considering implementation of CT screening in a general population. The ImaLife (Imaging in Lifelines) study, embedded in the Lifelines study, is designed to establish the reference values of the imaging biomarkers for the big three diseases in a well-defined general population aged 45 years and older. In total, 12,000 participants will undergo CACS and chest acquisitions with latest CT technology. The estimated percentage of individuals with lung nodules needing further workup is around 1-2%. Given the around 10% prevalence of COPD and CAD in the general population, the expected number of COPD and CAD is around 1000 each. So far, nearly 4000 participants have been included. The ImaLife study will allow differentiation between normal aging of the pulmonary and cardiovascular system and early stages of the big three diseases based on low-dose CT imaging. This information can be finally integrated into personalized precision health strategies in the general population.

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Aims Screening for a high cardiovascular disease (CVD) risk followed by preventive treatment can potentially reduce coronary heart disease-related morbidity and mortality. ROBINSCA (Risk Or Benefit IN Screening for CArdiovascular disease) is a population-based randomized controlled screening trial that investigates the effectiveness of CVD screening in asymptomatic participants using the Systematic COronary Risk Evaluation (SCORE) model or coronary artery calcium (CAC) scoring. This study describes the distributions in risk and treatment in the ROBINSCA trial. Methods and results Individuals at expected elevated CVD risk were randomized into screening arm A (n = 14 478; SCORE, 10-year fatal and non-fatal risk); or screening arm B (n = 14 450; CAC scoring). Preventive treatment was largely advised according to current Dutch guidelines. Risk and treatment differences between the screening arms were analysed. A total of 12 185 participants (84.2%) in arm A and 12 950 (89.6%) in arm B were screened. In total, 48.7% were women, and median age was 62 (interquartile range 10) years. SCORE screening identified 45.1% at low risk (SCORE < 10%), 26.5% at intermediate risk (SCORE 10–20%), and 28.4% at high risk (SCORE ≥ 20%). According to CAC screening, 76.0% were at low risk (Agatston < 100), 15.1% at high risk (Agatston 100–399), and 8.9% at very high risk (Agatston ≥ 400). CAC scoring significantly reduced the number of individuals indicated for preventive treatment compared to SCORE (relative reduction women: 37.2%; men: 28.8%). Conclusion We showed that compared to risk stratification based on SCORE, CAC scoring classified significantly fewer men and women at increased risk, and less preventive treatment was indicated. Trial registration number NTR6471.

Introduction A teachable moment for preventive behavioural change can occur when asymptomatic individuals receive their cardiovascular disease screening result. This study investigated prevention-seeking behaviour and compliance with preventive treatment of participants of the population-based Risk Or Benefit IN Screening for CArdiovascular disease (ROBINSCA) trial after receiving a screening result. Methods Asymptomatic Dutch individuals ( n = 43,447) were randomly assigned (1:1:1) to screening for cardiovascular disease by either traditional risk assessment (intervention arm A), or determining the amount of coronary artery calcification (intervention arm B), or to usual care (control arm). A random sample ( n = 600) of ROBINSCA participants with a screening result (arms A and B) received an online questionnaire (in 2017) to measure the impact of a cardiovascular disease screening result in low and increased (arm A: risk > 10%; arm B: Agatston ≥ 100) risk groups. Results Of all respondents (438/600; 73%) 63.5% were men and the mean age ( ± standard deviation) was 63.8 ± 6.9 years. Individuals with an increased coronary artery calcification score consulted their general practitioner more often compared to increased risk individuals from arm A: 140/149 (94%) and 86/137 (62.8%), respectively ( P < 0.001). Current use of blood pressure and cholesterol-lowering drugs was significantly higher in the increased coronary artery calcification score group (108/140; 77.1%), compared to the group with an increased traditional risk (35/80, 43.8%; P < 0.001). Self-reported compliance was high (98.1–100%). Conclusion Receiving the screening result might be a teachable moment that can enhance cardiovascular disease prevention-seeking behaviour through consulting a general practitioner and high compliance with preventive treatment. The impact of the screening result was more profound in the increased coronary artery calcification score group. Trial registration number: NTR6471

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