BackgroundThe significant increase in the average life expectancy has increased the societal challenge of managing serious age-related diseases, especially cancer and cardiovascular diseases. A routine check by a general practitioner is not sufficient to detect incipient cardiovascular disease.DesignPopulation-based randomized clinically controlled screening trial.MethodsParticipants: 45,000 Danish men aged 65–74 years living on the Island of Funen, or in the surrounding communities of Vejle and Silkeborg. No exclusion criteria are used.Interventions: One-third will be invited to cardiovascular seven-faceted screening examinations at one of four locations. The screening will include: (1) low-dose non-contrast CT scan to detect coronary artery calcification and aortic/iliac aneurysms, (2) brachial and ankle blood pressure index to detect peripheral arterial disease and hypertension, (3) a telemetric assessment of the heart rhythm, and (4) a measurement of the cholesterol and plasma glucose levels. Up-to-date cardiovascular preventive treatment is recommended in case of positive findings.Objective: To investigate whether advanced cardiovascular screening will prevent death and cardiovascular events, and whether the possible health benefits are cost effective.Outcome: Registry-based follow-up on all cause death (primary outcome), and costs after 3, 5 and 10 years (secondary outcome).Randomization: Each of the 45,000 individuals is, by EPIDATA, given a random number from 1–100. Those numbered 67+ will be offered screening; the others will act as a control group.Blinding: Only those randomized to the screening will be invited to the examination;the remaining participants will not.Numbers randomized: A total of 45,000 men will be randomized 1:2.Recruitment: Enrollment started October 2014.Outcome: A 5 % reduction in overall mortality (HR = 0.95), with the risk for a type 1 error = 5 % and the risk for a type II error = 80 %, is expected. We expect a 2-year enrollment, a 10-year follow-up, and a median survival of 15 years among the controls. The attendance to screening is assumed to be 70 %.DiscussionThe primary aim of this so far stand-alone population-based, randomized trial will be to evaluate the health benefits and costeffectiveness of using non-contrast full truncus computer tomography (CT) scans (to measure coronary artery calcification (CAC) and identify aortic/iliac aneurysms) and measurements of the ankle brachial blood pressure index (ABI) as part of a multifocal screening and intervention program for CVD in men aged 65–74.Attendance rate and compliance to initiated preventive actions must be expected to become of major importance.Trial registrationCurrent Controlled Trials: ISRCTN12157806 (21 March 2015).

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Patients with low/intermediate CAD risk and a positive CCTA scan represent a challenge to perfusion techniques indicated by the low sensitivity of both CMR and MPS with FFR as a reference. The mechanisms underlying this discrepancy need further investigation.

BackgroundCoronary computed tomography angiography (CCTA) is an established method for ruling out coronary artery disease (CAD). Most patients referred for CCTA do not have CAD and only approximately 20–30 % of patients are subsequently referred to further testing by invasive coronary angiography (ICA) or non-invasive perfusion evaluation due to suspected obstructive CAD. In cases with severe calcifications, a discrepancy between CCTA and ICA often occurs, leading to the well-described, low-diagnostic specificity of CCTA. As ICA is cost consuming and involves a risk of complications, an optimized algorithm would be valuable and could decrease the number of ICAs that do not lead to revascularization.The primary objective of the Dan-NICAD study is to determine the diagnostic accuracy of cardiac magnetic resonance imaging (CMRI) and myocardial perfusion scintigraphy (MPS) as secondary tests after a primary CCTA where CAD could not be ruled out. The secondary objective includes an evaluation of the diagnostic precision of an acoustic technology that analyses the sound of coronary blood flow. It may potentially provide better stratification prior to CCTA than clinical risk stratification scores alone.Methods/designDan-NICAD is a multi-centre, randomised, cross-sectional trial, which will include approximately 2,000 patients without known CAD, who were referred to CCTA due to a history of symptoms suggestive of CAD and a low-risk to intermediate-risk profile, as evaluated by a cardiologist. Patient interview, sound recordings, and blood samples are obtained in connection with the CCTA. All patients with suspected obstructive CAD by CCTA are randomised to either stress CMRI or stress MPS, followed by ICA with fractional flow reserve (FFR) measurements. Obstructive CAD is defined as an FFR below 0.80 or as high-grade stenosis (>90 % diameter stenosis) by visual assessment.Diagnostic performance is evaluated as sensitivity, specificity, predictive values, likelihood ratios, and C statistics. Enrolment commenced in September 2014 and is expected to be complete in May 2016.DiscussionDan-NICAD is designed to assess whether a secondary perfusion examination after CCTA could safely reduce the number of ICAs where revascularization is not required. The results are expected to add knowledge about the optimal algorithm for diagnosing CAD.Trial registrationClinicaltrials.gov identifier, NCT02264717. Registered on 26 September 2014.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1388-z) contains supplementary material, which is available to authorized users.

Aims-Cystatin C and cathepsins could play a role in different processes and stages of the atherosclerotic disease. We aimed to investigate the relationship of cystatin C, and cathepsins L, and S, to lethal outcome in patients with peripheral arterial disease (PAD).Methods and results-We studied 378 patients with established PAD. Cox regression was used to assess relationships between serum cystatin C or cathepsins L and S, and time to lethal outcome. The role of cystatin for prognosis of cardiovascular death was assessed with c-statistic, and net reclassification improvement (NRI). Patients with cystatin C levels above 1 mg/l (fifth quintile) had a significantly increased adjusted risk for all-cause and cardiovascular mortality compared to patients with cystatin C levels below or equal to 1 mg/l (hazard ratios (HR) 2.2, 95% CI 1.22-4.12, and HR 3.2, 95% CI 1.39-7.59, respectively). Furthermore, high cystatin C levels were related with higher all-cause (adjusted HR 2.99, 95% CI 1.31-6.85) and cardiovascular mortality (adjusted HR 4.36, 95% CI 1.07-18.8) among PAD patients without renal impairment. Although the addition of cystatin C to conventional risk factors improved the accuracy of risk prediction model for cardiovascular mortality (0.72-0.79; p = 0.03), it did not reclassify a substantial proportion of patients to risk categories (NRI = 0.12, p = 0.128).Conclusions-Higher cystatin C levels independently predicted 5 years all-cause, and cardiovascular death in PAD patients. However, a small improvement in discrimination with the addition of cystatin C to conventional risk factors, and no improvement in reclassification of risk categories suggest that clinical usefulness of cystatin C for predicting cardiovascular mortality in PAD population might be modest.