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Aims A recent trial has shown that screening of men for cardiovascular disease (CVD) may reduce all-cause mortality. This study assesses the cost effectiveness of such screening vs. no screening from the perspective of European healthcare systems. Methods and results Randomized controlled trial-based cost-effectiveness evaluation with a mean 5.7 years of follow-up. Screening was based on low-dose computed tomography to detect coronary artery calcification and aortic/iliac aneurysms, limb blood pressure measurement to detect peripheral artery disease and hypertension, telemetric assessment of the heart rhythm to detect atrial fibrillation, and measurements of the cholesterol and HgbA1c levels. Censoring-adjusted incremental costs, life years (LY), and quality-adjusted LY (QALY) were estimated and used for cost-effectiveness analysis. The incremental cost of screening for the entire health care sector was €207 [95% confidence interval (CI) −24; 438, P = 0.078] per invitee for which gains of 0.019 LY (95% CI −0.007; 0.045, P = 0.145) and 0.023 QALY (95% CI −0.001; 0.046, P = 0.051) were achieved. The corresponding incremental cost-effectiveness ratios were of €10 812 per LY and €9075 per QALY, which would be cost effective at probabilities of 0.73 and 0.83 for a willingness to pay of €20 000. Assessment of population heterogeneity showed that cost effectiveness could be more attractive for younger men without CVD at baseline. Conclusions Comprehensive screening for CVD is overall cost effective at conventional thresholds for willingness to pay and also competitive to the cost effectiveness of common cancer screening programmes. The screening target group, however, needs to be settled.

Background: Menaquinone-7 (MK-7), also known as vitamin K2, is a cofactor for the carboxylation of proteins involved in the inhibition of arterial calcification and has been suggested to reduce the progression rate of aortic valve calcification (AVC) in patients with aortic stenosis. Methods: In a randomized, double-blind, multicenter trial, men from the community with an AVC score >300 arbitrary units (AU) on cardiac noncontrast computer tomography were randomized to daily treatment with tablet 720 µg MK-7 plus 25 µg vitamin D or matching placebo for 24 months. The primary outcome was the change in AVC score. Selected secondary outcomes included change in aortic valve area and peak aortic jet velocity on echocardiography, heart valve surgery, change in aortic and coronary artery calcification, and change in dp-ucMGP (dephosphorylated-undercarboxylated matrix Gla-protein). Safety outcomes included all-cause death and cardiovascular events. Results: From February 1, 2018, to March 21, 2019, 365 men were randomized. Mean age was 71.0 (±4.4) years. The mean (95% CI) increase in AVC score was 275 AU (95% CI, 225–326 AU) and 292 AU (95% CI, 246–338 AU) in the intervention and placebo groups, respectively. The mean difference on AVC progression was 17 AU (95% CI, –86 to 53 AU; P =0.64). The mean change in aortic valve area was 0.02 cm 2 (95% CI, –0.09 to 0.12 cm 2 ; P =0.78) and in peak aortic jet velocity was 0.04 m/s (95% CI, –0.11 to 0.02 m/s; P =0.21). The progression in aortic and coronary artery calcification score was not significantly different between patients treated with MK-7 plus vitamin D and patients receiving placebo. There was no difference in the rate of heart valve surgery (1 versus 2 patients; P =0.99), all-cause death (1 versus 4 patients; P =0.37), or cardiovascular events (10 versus 10 patients; P =0.99). Compared with patients in the placebo arm, a significant reduction in dp-ucMGP was observed with MK-7 plus vitamin D (–212 pmol/L versus 45 pmol/L; P Conclusions: In elderly men with an AVC score >300 AU, 2 years MK-7 plus vitamin D supplementation did not influence AVC progression. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03243890.

PURPOSE: Further diagnostic testing may be required after a coronary computed tomography angiography (CTA) showing suspected coronary stenosis. Whether myocardial perfusion imaging (MPI) provides further prognostic information post-CTA remains debated. We evaluated the prognosis for patients completing CTA stratified for post-CTA diagnostic work-up using real-world data.METHODS: We identified all patients in our uptake area with angina symptoms undergoing first-time CTA over a 10-year period. Follow-up time was a median of 3.7 years [1.9-5.8]. The primary endpoint was a composite of myocardial infarction or death. The secondary endpoint was late revascularization.RESULTS: During the study period 53,351 patients underwent CTA. Of these, 24% were referred for further down-stream testing, 3,547 (7%) to MPI and 9,135 (17%) to invasive coronary angiography (ICA). The primary and secondary endpoints occurred in 2,026 (3.8%) and 954 (1.8%) patients. Patient-characteristic-adjusted hazard ratios for the primary and secondary endpoint using patients with a normal CTA as reference were 1.37 (1.21-1.55) and 2.50 (1.93-3.23) for patient treated medically, 1.68 (1.39-2.03) and 6.13 (4.58-8.21) for patients referred to MPI and 1.94 (1.69-2.23) and 9.18 (7.16-11.78) for patients referred for ICA, respectively. Adjusted analysis with stratification for disease severity at CTA showed similar hazard ratios for patients treated medically after CTA and patients referred for MPI and treated medically after the MPI.CONCLUSION: In patients completing coronary CTA, second-line MPI testing seems to identify patients at low risk of future events. MPI seems to have the potential to act as gatekeeper for ICA after coronary CTA.

Aims Aortic valve calcification (AVC) detected by non-contrast computed tomography (NCCT) associates with morbidity and mortality in patients with aortic valve stenosis. However, the importance of AVC in the general population is sparsely evaluated. We intend to describe the associations between AVC score on NCCT and echocardiographic findings as left atrial (LA) dilatation, left ventricular (LV) hypertrophy, aortic valve area (AVA), peak velocity, mean gradient, and aortic valve replacement (AVR) in a population with AVC scores ≥300 AU. Methods and results Of 10 471 males aged 65–74 years from the Danish Cardiovascular Screening trial (DANCAVAS), participants with AVC score ≥300 AU were invited for transthoracic echocardiography and 828 (77%) of 1075 accepted the invitation. AVC scores were categorized (300–599, 600–799, 800–1199, and ≥1200 AU). AVR was obtained from registries. AVC was significantly associated with a steady increase in LA dilation (10.5%, 16.3%, 15.8%, 19.6%, P = 0.031), LV hypertrophy (3.9%, 6.6%, 8.9%, 10.1%, P = 0.021), peak velocity (1.7, 1.9, 2.1, 2.8 m/s, P = 0001), mean gradient (6, 8, 11, 19 mmHg, P = 0.0001), and a decrease in AVA (2.0, 1.9, 1.7, 1.3 cm2, P = 0.0001). The area under the curve was 0.79, 0.93, and 0.92 for AVA ≤1.5 cm2, peak velocity ≥3.0 m/s, and mean gradient ≥20 mmHg, respectively, and the associated optimal AVC score thresholds were 734, 1081, and 1019 AU. AVC > 1200 AU was associated with AVR (P Conclusion Among males from the background population, increasing AVC scores were associated with LA dilatation, LV hypertrophy, AVA, peak aortic velocity, mean aortic gradient, and AVR.

ObjectiveAortic valve calcification (AVC) and coronary artery calcification (CAC) are predictors of cardiovascular disease (CVD), presumably sharing risk factors. Our objectives were to determine the prevalence and extent of AVC in a large population of men aged 60–74 years and to assess the association between AVC and cardiovascular risk factors including CAC and biomarkers.MethodsParticipants from the DANish CArdioVAscular Screening and intervention trial (DANCAVAS) with AVC and CAC scores and without previous valve replacement were included in the study. Calcification scores were calculated on non-contrast CT scans. Cardiovascular risk factors were self-reported, measured or both, and further explored using descriptive and regression analysis for AVC association.Results14 073 men aged 60–74 years were included. The AVC scores ranged from 0 to 9067 AU, with a median AVC of 6 AU (IQR 0–82). In 8156 individuals (58.0%), the AVC score was >0 and 215 (1.5%) had an AVC score ≥1200. In the regression analysis, all cardiovascular risk factors were associated with AVC; however, after inclusion of CAC ≥400, only age (ratio of expected counts (REC) 1.07 (95% CI 1.06 to 1.09)), hypertension (REC 1.24 (95% CI 1.09 to 1.41)), obesity (REC 1.34 (95% CI 1.20 to 1.50)), known CVD (REC 1.16 (95% CI 1.03 to 1.31)) and serum phosphate (REC 2.25 (95% CI 1.66 to 3.10) remained significantly associated, while smoking, diabetes, hyperlipidaemia, estimated glomerular filtration rate and serum calcium were not.ConclusionsAVC was prevalent in the general population of men aged 60–74 years and was significantly associated with all modifiable cardiovascular risk factors, but only selectively after adjustment for CAC ≥400 AU.Trial registration numberNCT03946410 and ISRCTN12157806.

Background: Type 2 diabetes mellitus (T2D) patients with albuminuria have coronary microvascular dysfunction (CMD). Fractional flow reserve assessed by coronary computed tomography angiography (FFRct) is dependent on the structure and function of the microcirculation and is likely influenced by CMD. We aimed to evaluate if asymptomatic patients with T2D who had no significant coronary artery stenosis but had been diagnosed with albuminuria had lower value of nadir FFRct compared to asymptomatic patients with T2D and no albuminuria. Methods and results: This was a cross-sectional study which compared the mean nadir FFRct values in coronary arteries in patients with T2D who had no symptoms of angina. The T2D patients were divided into two groups (albuminuria and no albuminuria) with albuminuria being defined as albumin–creatinine-ratio (ACR) ≥30 milligram per gram. The nadir FFRct values were compared between the two groups for left anterior descendent artery (FFRct-LAD), circumflex artery (FFRct-CX), and right coronary artery (FFRct-RCA) by using a two-sample Wilcoxon rank-sum (Mann–Whitney) test. Ninety-eight patients without albuminuria and 26 patients with albuminuria were included. No significant differences in mean values were detected for FFRct-CX 0.86 ± 0.07 and 0.88 ± 0.0, FFRct-RCA 0.88 ± 0.05 and 0.88 ± 0.07, or for FFRct-LAD 0.82 ± 0.07 and 0.82 ± 0.07 in patients with albuminuria and without albuminuria, respectively. Conclusion: In this observational study, we did not find that FFRct was affected by CMD. Therefore, it is not a surrogate for microvascular dysfunction in asymptomatic T2D patients with albuminuria.

Aims Coronary artery calcification (CAC) measured on cardiac computed tomography (CT) is an important risk marker for cardiovascular disease (CVD) and has been included in the prevention guidelines. The aim of this study was to describe CAC score reference values in the middle-aged and elderly population and to develop a freely available CAC calculator. Methods and results All participants from two population-based cardiac CT screening cohorts (DanRisk and DANCAVAS) were included. The CAC score was measured as a part of a screening session. Positive CAC scores were log-transformed and non-parametrically regressed on age for each gender, and percentile curves were transposed according to proportions of zero CAC scores. Men had higher CAC scores than women, and the prevalence and extend of CAC increased steadily with age. An online CAC calculator was developed, http://flscripts.dk/cacscore. After entering sex, age, and CAC score, the CAC score percentile and the coronary age are depicted including a figure with the specific CAC score and 25%, 50%, 75%, and 90% percentiles. The specific CAC score can be compared to the entire background population or only those without prior CVD. Conclusion This study provides modern population-based reference values of CAC scores in men and woman and a freely accessible online CAC calculator. Physicians and patients are very familiar with blood pressure and lipids, but unfamiliar with CAC scores. Using the calculator makes it easy to see if a CAC value is low, moderate, or high, when a physician in the future communicate and discusses a CAC score with a patient.

BACKGROUND: Limited data suggest a benefit of population-based screening for cardiovascular disease with respect to the risk of death.METHODS: We performed a population-based, parallel-group, randomized, controlled trial involving men 65 to 74 years of age living in 15 Danish municipalities. The participants were randomly assigned in a 1:2 ratio to undergo screening (the invited group) or not to undergo screening (the control group) for subclinical cardiovascular disease. Randomization was based on computer-generated random numbers and stratified according to municipality. Only the control group was unaware of the trial-group assignments. Screening included noncontrast electrocardiography-gated computed tomography to determine the coronary-artery calcium score and to detect aneurysms and atrial fibrillation, ankle-brachial blood-pressure measurements to detect peripheral artery disease and hypertension, and a blood sample to detect diabetes mellitus and hypercholesterolemia. The primary outcome was death from any cause.RESULTS: A total of 46,611 participants underwent randomization. After exclusion of 85 men who had died or emigrated before being invited to undergo screening, there were 16,736 men in the invited group and 29,790 men in the control group; 10,471 of the men in the invited group underwent screening (62.6%). In intention-to-treat analyses, after a median follow-up of 5.6 years, 2106 men (12.6%) in the invited group and 3915 men (13.1%) in the control group had died (hazard ratio, 0.95; 95% confidence interval [CI], 0.90 to 1.00; P = 0.06). The hazard ratio for stroke in the invited group, as compared with the control group, was 0.93 (95% CI, 0.86 to 0.99); for myocardial infarction, 0.91 (95% CI, 0.81 to 1.03); for aortic dissection, 0.95 (95% CI, 0.61 to 1.49); and for aortic rupture, 0.81 (95% CI, 0.49 to 1.35). There were no significant between-group differences in safety outcomes.CONCLUSIONS: After more than 5 years, the invitation to undergo comprehensive cardiovascular screening did not significantly reduce the incidence of death from any cause among men 65 to 74 years of age. (Funded by the Southern Region of Denmark and others; DANCAVAS ISRCTN Registry number, ISRCTN12157806.).

To investigate the impact of combining the high-resolution (Hi-res) scan mode with deep learning image reconstruction (DLIR) algorithm in CT. Two phantoms (Catphan600® and Lungman, small, medium, large size) were CT scanned using combinations of Hi-res/standard mode and high-definition (HD)/standard kernels. Images were reconstructed with ASiR-V and three levels of DLIR. Spatial resolution, noise and contrast-to-noise ratio (CNR) were assessed. The radiation dose was recorded. The spatial resolution increased using Hi-res & HD. Image noise in the Catphan600® (69%) and the Lungman (10–70%) significantly increased when Hi-res & HD was applied. DLIR reduced the mean noise (54%). The CNR was reduced (64%) for Hi-res & HD. The radiation dose increased for both small (+70%) and medium (+43%) Lungman phantoms but decreased slightly for the large ones (−3%) when Hi-res was applied. In conclusion, the Hi-res scan mode improved the spatial resolution. The HD kernel significantly increased the image noise. DLIR improved the image noise and CNR and did not affect the spatial resolution.

BACKGROUND: Enlargement of left atrium (LA) is a valuable marker of cardiovascular events, and LA size is readily available while performing non-contrast cardiac computed tomography (NCCT) for preventive purposes. We aimed to evaluate the predictive value of a single LA area from NCCT in a population-based cohort.METHOD: Mainly men aged 60-75 years from DANCAVAS were included. Traditional risk factors were recorded, and an NCCT scan performed at baseline. Coronary artery calcifications (CAC) score and the largest LA area were measured. LA was indexed to body surface area and categorised into four groups. Data on incident atrial fibrillation (AF), thromboembolic events, heart failure (HF) and death were obtained from Danish national registries.RESULTS: In total, 14,557 individuals were eligible, excluding those without LA measurement (N = 232) and with heart valve replacement (N = 197). Known AF or HF were respectively excluded from follow-up. Median follow-up time was 2.1 to 3.4 years. In total, 304 developed AF, 149 had thromboembolism, 129 developed HF and 482 died. In adjusted analysis, LA enlargement was associated with AF (HR (95% CI): large 1.99 (1.46-2.71) and very large LA 3.77 (2.31-6.14)) and HF (large 2.40 (1.50-3.85) and very large LA 6.54 (4.07-10.51)). A very large LA significantly increased mortality (HR: 2.01 (1.44-2.82)), and was associated with a two-fold increased risk of thromboembolism; however, not significantly in adjusted analysis (p = 0.09).CONCLUSION: We demonstrated that determination of LA area from NCCT was an important predictor of AF, HF and death. This knowledge could inform current risk assessment beyond CAC score.

Aims To investigate the impact of applying coronary computed tomography angiography (CCTA), as the recommended first-line diagnostic test in patients with suspected chronic coronary syndrome (CCS) on the use of invasive coronary angiography (ICA) and revascularization practice. Methods and results We included all patients undergoing a first-time CCTA (n = 53555) and first-time ICA (n = 41451) from 2008 to 2017 due to suspected CCS in Western Denmark (3.3 million inhabitants). The number of CCTA procedures increased from 352 (2008) to 7739 (2017) (2098%), ICA examinations declined from 4538 to 3766 (17%). The average proportion of no- or non-obstructive coronary artery disease by CCTA was 77.5%. Referral to ICA after CCTA occurred in 16.9% of patients in 2008–10 vs. 13.9% in 2014–17 (P 70 years: 9.5% decrease. Conclusion The introduction of CCTA as a first-line diagnostic test in patients with suspected CCS does not associate with increased use of invasive angiography and seems to have facilitated a more appropriate revascularization practice.

Jes S Lindholt, 1–3 Axel C Diederichsen, 2, 4 Lars M Rasmussen, 2, 5 Lars Frost, 6, 7 Flemming H Steffensen, 8 Jess Lambrechtsen, 8 Grazina Urbonaviciene, 6, 7 Martin Busk, 9 Kenneth Egstrup, 8 Katrine L Kristensen, 1–3 Carsten Behr Andersen, 3 Rikke Søgaard 10 1Department of Cardiothoracic and Vascular Surgery, Odense University Hospital, Odense, Denmark; 2Elitary Centre for Individualized Medicine in Arterial Diseases (CIMA), Odense, Denmark; 3Department of Vascular Surgery, Viborg Hospital, Viborg, Denmark; 4Department of Cardiology, Odense University Hospital, Odense, Denmark; 5Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark; 6Department of Cardiology, Diagnostic Centre, Regional Hospital Silkeborg, Silkeborg, Denmark; 7Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; 8Department of Cardiology, Vejle Hospital, Vejle, Denmark; 9Department of Cardiology, University Hospital Odense Svendborg, Svendborg, Denmark; 10Department of Public Health and Department of Clinical Medicine, Aarhus University, Aarhus, DenmarkCorrespondence: Jes S LindholtDepartment of Cardiothoracic and Vascular Surgery, Odense University Hospital, J.B. Winsløv Vej 4, Odense 5000, DenmarkTel +45 2464 1214Email Jes.sanddal.lindholt@rsyd.dkAim: The prevalence and mortality of abdominal aortic aneurysms (AAA) has been reported to decline. The aim of this study is to compare survival, prevalence, and repair rate of AAA in Denmark in the 1990s, the 2000s and the 2010s – and to examine any change in factors known to influence the prevalence.Methods: Baseline status and up to 5-year outcomes of 34,079 general population men aged 65– 74 were obtained from three RCTs; the Viborg study (1994– 1998, n=4,860), the Viborg Vascular (VIVA) trial (2008– 2011, n=18,748), and the Danish Cardiovascular (DANCAVAS) trial (2015– 2018, n=10,471). After the millennium (VIVA and DANCAVAS) men with AAA were further offered low dose aspirin and statins. Follow-up data were not available for the DANCAVAS trial yet.Results: Across the three decades, the AAA prevalence was 3.8% (Reference), 3.3% (p< 0.001) and 4.2% (p=0.882), the proportion of smokers were 62%, 42% and 34% (p< 0.001) amongst men with AAA, but AAA risk associations with smoking increased during the decades suggesting increased tobacco consumption of smokers. In addition, the proportions of attenders with ischemic heart disease or stroke increased significantly. The aneurysmal progression rate in the 1990s was 2.90 vs 2.98 mm/year in the 2000s (p=0.91). The need for preventive AAA repair increased insignificantly in the 2000s (Age adj. HR= 1.29, 95% C.I.: 0.95; 1.71, p=0.10), and mortality of men with screen-detected AAA was lower in the 2000s compared to the 1990s (Age-adj. HR= 0.28, 95% C.I.: 0.22; 0.36, p< 0.001).Conclusion: The Danish prevalence of AAA today compares to the nineties. Unchanged aneurysmal progression rates combined with improved survival of men at risk of AAA leave them in longer time to develop an AAA, be diagnosed and to need later aneurysmal repair or experience rupture.Clinical Trial Registrations: Viborg study: No possibility of registration in the nineties. VIVA: NCT00662480, URL: https://clinicaltrials.gov/show/NCT00662480, DANCAVAS: ISRCTN12157806, URL: http://www.isrctn.com/ISRCTN12157806.Keywords: abdominal aortic aneurysms, screening, prevalence, survival, progression, smoking

Purpose: When performing coronary computed tomography angiography (CCTA) in obese patients, it is a challenge to obtain diagnostic image quality. Theoretically, higher tube currents improve image quality in obese patients by reducing noise, but this comes with an increased radiation as a trade-off. Deep learning image reconstruction (DLIR) is a technique that should reduce noise and improve image quality without the need of a higher radiation dose. This study assessed the impact of higher tube currents and DLIR on image quality, diagnostic utility, and noise. Methods: The study consisted of 51 symptomatic obese (BMI > 30 kg/m 2 ) patients with low to moderate risk of coronary artery disease (CAD). All patients underwent CCTA twice, first with the Revolution CT scanner and then with the upgraded Revolution Apex scanner with the ability to increase tube currents. Images were reconstructed using ASiR-V 50% and DLIR and evaluated by an observer using a Likert score. Results: Image quality was significantly improved with the Revolution Apex scanner and reconstruction with DLIR, resulting in an odds ratio of 1,23 (p = 0,017), and noise was significantly reduced by 41%. Diagnostic utility was also improved with 88% vs. 69% “diagnostic” image sets of those performed with Revolution Apex + DLIR and Revolution Apex/CT + ASiR-V, respectively. No significant differences were found between Revolution CT and Revolution Apex when reconstructing with ASiR-V. Conclusion: In obese patients, the combination of higher tube currents and reconstruction with DLIR significantly improves the subjective image quality and diagnostic utility and reduces noise.

BackgroundHigh-risk coronary artery plaque (HRP) is associated with increased risk of acute coronary syndrome.We aimed to investigate the prevalence of HRP in asymptomatic patients with type 2 diabetes (T2D), and its relation to patient characteristics including cardiovascular risk factors, diabetes profile, and coronary artery calcium score (CACS).MethodsAsymptomatic patients with T2D and no previous coronary artery disease (CAD) were studied using coronary computed tomography angiography (CCTA) in this descriptive study. Plaques with two or more high-risk features (HRP) defined by low attenuation, positive remodeling, spotty calcification, and napkin-ring sign were considered HRP. In addition, total atheroma volume (TAV), proportions of dense calcium, fibrous, fibrous-fatty and necrotic core volumes were assessed. The CACS was obtained from non-enhanced images by the Agatston method. Cardiovascular and diabetic profiles were assessed in all patients.ResultsIn 230 patients CCTA was diagnostic and 161 HRP were detected in 86 patients (37%). Male gender (OR 4.19, 95% CI 1.99–8.87; p ConclusionA high prevalence of HRP was detected in this population of asymptomatic T2D. The presence of HRP was associated with a particular patient profile, but was not ruled out by the absence of coronary artery calcium. CCTA provides important information on plaque morphology, which may be used to risk stratify this high-risk population.Trial registrationThis trial was retrospectively registered at clinical trials.gov January 11, 2017 trial identifier NCT03016910.

Background Aortic dilations (ectasias and aneurysms) may occur on any segment of the aorta. Pathogenesis varies between locations, suggesting that etiology and risk factors may differ. Despite this discrepancy, guidelines recommend screening of the whole aorta if 1 segmental dilation is discovered. Objectives The purpose of this study was to determine the most dominant predictors for dilations at the ascending, arch, descending, and abdominal part of the aorta, and to establish comprehensive risk factor profiles for each aortic segment. Methods Individuals aged 60-74 years were randomly selected to participate in DANCAVAS I+II (Danish Cardiovascular Multicenter Screening Trials). Participants underwent cardiovascular risk assessments, including blood samples, blood pressure readings, medical records, and noncontrast computed tomography scans. Adjusted odds ratios for potential risk factors of dilations were estimated by multivariate logistic analyses. Results The study population consisted of 14,989 participants (14,235 men, 754 women) with an average age of 68 ± 4 years. The highest adjusted odd ratios for having any aortic dilation were observed when coexisting aortic dilations were present. Other noteworthy predictors included coexisting iliac dilations, hypertension, increasing body surface area, male sex, familial disposition, and atrial fibrillation, which were present in various combinations for the different aortic parts. Smoking and acute myocardial infarction were inversely associated with ascending and abdominal dilations. Diabetes was a shared protective factor. Conclusions Risk factors differ for aortic dilations between locations. The most dominant predictor for having a dilation at any aortic segment is the presence of an aortic dilation elsewhere. This supports current guidelines when recommending a full screening of the aorta if a focal aortic dilation is discovered.

Background The challenge of managing age-related diseases is increasing; routine checks by the general practitioner do not reduce cardiovascular mortality. The aim here was to reduce cardiovascular mortality by advanced population-based cardiovascular screening. The present article reports the organization of the study, the acceptability of the screening offer, and the relevance of multifaceted screening for prevention and management of cardiovascular disease. Methods Danish men aged 65–74 years were invited randomly (1 : 2) to a cardiovascular screening examination using low-dose non-contrast CT, ankle and brachial BP measurements, and blood tests. Results In all, 16 768 of 47 322 men aged 65–74 years were invited and 10 471 attended (uptake 62·4 per cent). Of these, 3481 (33·2 per cent) had a coronary artery calcium score above 400 units. Thoracic aortic aneurysm was diagnosed in the ascending aorta (diameter 45 mm or greater) in 468 men (4·5 per cent), in the arch (at least 40 mm) in 48 (0·5 per cent) and in the descending aorta (35 mm or more) in 233 (2·2 per cent). Abdominal aortic aneurysm (at least 30 mm) and iliac aneurysm (20 mm or greater) were diagnosed in 533 (5·1 per cent) and 239 (2·3 per cent) men respectively. Peripheral artery disease was diagnosed in 1147 men (11·0 per cent), potentially uncontrolled hypertension (at least 160/100 mmHg) in 835 (8·0 per cent), previously unknown atrial fibrillation confirmed by ECG in 50 (0·5 per cent), previously unknown diabetes mellitus in 180 (1·7 per cent) and isolated severe hyperlipidaemia in 48 men (0·5 per cent). In all, 4387 men (41·9 per cent), excluding those with potentially uncontrolled hypertension, were referred for additional cardiovascular prevention. Of these, 3712 (35·5 per cent of all screened men, but 84·6 per cent of those referred) consented and were started on medication. Conclusion Multifaceted cardiovascular screening is feasible and may optimize cardiovascular disease prevention in men aged 65–74 years. Uptake is lower than in aortic aneurysm screening.

ObjectiveTransition towards value-based healthcare requires insight into what makes value to the individual. The aim was to elicit individual preferences for cardiovascular disease screening with respect to the difficult balancing of good and harm as well as mode of delivery.MethodsA discrete choice experiment was conducted as a cross-sectional survey among 1231 male screening participants at three Danish hospitals between June and December 2017. Participants chose between hypothetical screening programmes characterised by varying levels of mortality risk reduction, avoidance of overtreatment, avoidance of regretting participation, screening duration and location. A multinomial mixed logit model was used to model the preferences and the willingness to trade mortality risk reduction for improvements on other characteristics.ResultsRespondents expressed preferences for improvements on all programme characteristics. They were willing to give up 0.09 (95% CI 0.08 to 0.09) lives saved per 1000 screened to avoid one individual being over treated. Similarly, respondents were willing to give up 1.22 (95% CI 0.90 to 1.55) or 5.21 (95% CI 4.78 to 5.67) lives saved per 1000 screened to upgrade the location from general practice to a hospital or to a high-tech hospital, respectively. Subgroup analysis revealed important preference heterogeneity with respect to smoking status, level of health literacy and self-perceived risk of cardiovascular disease.ConclusionsIndividuals are able to express clear preferences about what makes value to them. Not only health benefit but also time with health professionals and access to specialised facilities were important. This information could guide the optimal programme design in search of value-based healthcare.

Current guidelines do not recommend coronary computed tomography angiography (CCTA) in patients with high levels of coronary calcium, as severe calcification leads to difficulties in estimating stenosis severity due to blooming artifacts obscuring the vessel lumen. Whether the CCTA-derived fractional flow reserve (FFRCT) improves the diagnostic performance of CCTA in patients with high levels of coronary calcification has not been sufficiently evaluated. We hypothesize that a noninvasive diagnostic strategy using FFRCT will perform comparably to an invasive diagnostic strategy in the detection of hemodynamically significant coronary artery disease (CAD) in clinical stable chest pain patients with high levels of coronary calcium. In this prospective, blinded, multicenter study, patients with suspected stable CAD referred for CCTA and demonstrating an Agatston score >399 will be included. Patients accepting inclusion will, in addition to CCTA, undergo invasive coronary angiography (ICA) and invasive FFR measurement. FFRCT analyses are performed by an external core laboratory blinded to any patient data, and the FFRCT results are blinded to all participating study sites. The primary objective is to evaluate whether FFRCT can identify patients with and without hemodynamically significant CAD, when ICA with FFR is the reference standard. A negative study result would question the clinical usefulness of FFRCT in patients with high levels of coronary calcium. A positive study result, however, would imply a reduction in the number of patients referred for coronary catheterization and, at the same time, increase the proportion of patients with hemodynamically significant CAD at the subsequent invasive examination.

The influence of extensive coronary calcifications on the diagnostic and prognostic value of coronary computed tomography angiography-derived fractional flow reserve (FFRThe purpose of this study was to investigate the diagnostic and short-term role of FFRThis was a prospective multicenter study of 260 stable patients with suspected coronary artery disease (CAD) and AS399. FFRMedian age and AS were 68.5 years (IQR: 63-74 years) and 895 (IQR: 587-1,513), respectively. FFRMost patients with AS399 had FFR

OBJECTIVE: The aim of this work was to evaluate the prognostic impact of statin therapy in symptomatic patients without obstructive CAD.BACKGROUND: Information on the prognostic impact of post-coronary computed tomographic angiography (CTA) statin use in patients with no or nonobstructive coronary artery disease (CAD) is sparse.METHODS: Patients undergoing CTA with suspected CAD in western Denmark from 2008 to 2017 with RESULTS: The study included 33,552 patients, median aged 56 years, 58% female, with no (n = 19,669) or nonobstructive (n = 13,883) CAD and a median follow-up of 3.5 years. The absolute risk of the combined end point of myocardial infarction (MI) or all-cause mortality was directly associated with the CAD burden with an event rate/1,000 patient-years of 4.13 (95% CI: 3.69-4.61) in no, 7.74 (95% CI: 6.88-8.71) in mild (coronary artery calcium score [CACS] 0-99), 13.72 (95% CI: 11.61-16.23) in moderate (CACS 100-399), and 32.47 (95% CI: 26.25-40.16) in severe (CACS ≥400) nonobstructive CAD. Statin therapy was associated with a multivariable adjusted HR for MI and death of 0.52 (95% CI: 0.36-0.75) in no, 0.44 (95% CI: 0.32-0.62) in mild, 0.51 (95% CI: 0.34-0.75) in moderate, and 0.52 (95% CI: 0.32-0.86) in severe nonobstructive CAD. The estimated numbers needed to treat to prevent the primary end point were 92 (95% CI: 61-182) in no, 36 (95% CI: 26-58) in mild, 24 (95% CI: 15-61) in moderate, and 13 (95% CI: 7-86) in severe nonobstructive CAD. Residual confounding may persist, but not to an extent explaining all of the observed risk reduction associated with statin treatment.CONCLUSIONS: The risk of MI and all-cause mortality in patients without obstructive CAD is directly associated with the CAD burden. Statin therapy is associated with a reduction of MI and all-cause death across the spectrum of CAD, however, the absolute benefit of treatment is directionally proportional with the CAD burden.

To determine individual, expected normal diameters of the ascending aorta (AAo) and prevalence of dilations based upon an absolute cut-off point (≥ 40 mm) and individual cut-off point (≥ 25% than expected normal). Non-contrast computed tomography (CT) scans were obtained in 14,993 individuals (95.0% male, mean age 67.8 ± 3.8). A sub-group (n = 291) had AAo diameter measured by transthoracic echocardiography. A prediction formula for AAo diameters was created from multivariate linear regression analysis based upon gender, age, and body surface area. An index was made by dividing observed diameters with predicted diameters. A size-index ≥ 1.25 was defined as dilated. Prevalence of AAo dilations among males and females using 40 mm as cut-off point were 10.6% and 2.1% (p

Cardiovascular disease is one of the main causes of death and disability in the Western world, and there is increasing evidence that air pollution is a risk factor for developing sub-clinical cardiovascular diseases. Previous studies have shown a correlation between cardiovascular disease and short-term exposure to elevated air pollution levels. However, the literature on the impact of long-term effect of air pollution is limited. We have a unique opportunity to evaluate this correlation. The DEHM/UBM/AirGIS model system calculates air pollution in a high temporal and spatial resolution and traces air pollution retrospectively to year 1979. The model calculates accumulated exposure using annual exposure from PM2.5 in relation to home and work addresses and takes into account working hours and holidays. We link the results from this model system to a population-based cardiovascular screening cohort of 33,723 individuals in the age of 60–74 to assess the contribution of the specific accumulated air pollution to the presence of sub-clinical arteriosclerosis in the coronary vessels, abdominal aortic aneurysms, and peripheral arterial disease. This correlation will be further analyzed in relation to specific air pollutants. This study will introduce more precise data for a longer period of time and incorporate participant’s home and work addresses.

Improvement of non-invasive identification of high-risk plaque may increase the preventive options of acute coronary syndrome. To describe the characteristics of thin-cap fibroatheroma (TCFA) in a post mortem model in comparison to characteristics of culprit lesions in patients with non-ST-elevation-myocardial-infarction (NSTEMI) using the dual energy computed tomography (DECT). Three post mortem hearts were prepared with iodine-contrast, inserted in a Kyoto phantom and scanned by DECT. Six TCFA were identified using histopathological analysis (cap thickness < 65 μm and necrotic core > 10% of the plaque area). In the NSTEMI group, 29 patients were scheduled to DECT prior to coronary angiography and invasive treatment. Culprit lesions were identified blinded for the patient history by two independent invasive cardiologists using the coronary angiography. The DECT analysis of TCFA and culprit lesions was performed retrospectively with determination of effective atomic number (Effective-Z), Hounsfield Unit (HU), plaque type (non-calcified, predominantly non-calcified, predominantly calcified or calcified), spotty calcification, plaque length, plaque volume and plaque burden and the remodeling index. The Effective-Z, HU and plaqueburden were significantly different between TCFA and culprit lesions (P < 0.05).The TCFA plaques were more calcified in comparison to culprit lesions (P < 0.05). No significant difference in the other plaque characteristics was observed. The use of DECT demonstrated different Effective-Z values and different characteristics of post mortem TCFA in comparison to in vivo culprit lesions. This finding may highlight, that not all TCFA should be considered as vulnerable.

Introduction Left atrial (LA) size is an independent predictor of cardiovascular outcome. While performing non-contrast computed tomography (NCCT), LA size is readily available, and a single cross-section area provides a accurate estimate of LA enlargement. Purpose The purpose of this study was to examine if enlarged LA measured by a NCCT scan was an independent risk factor of subsequent atrial fibrillation or flutter (AF). Methods The Cardiovascular Screening Trial; a population-based multicenter randomized screening trial, consisting primarily of men aged 60–74 years were randomly allocated (1:2) for screening. NCCT was performed and LA area was manually traced in a single axial slice excluding the pulmonary veins at mitral valve level. LA size was indexed to body surface area. Indexed LA area was divided into five categories (defined by standard deviations). Hospital admission due to AF were identified using data from the National Patient Registry using ICD-10 codes (DI48-DI489). Results Between 2014 and 2019, 14,986 participants were enrolled, of these 13,410 without known AF were eligible for follow-up. During 2.3±1.0 years of follow-up 301 developed incident AF, corresponding to an incidence rate of 10.0 per 1,000 person-years. Figure 1 shows the Kaplan-Meier of incident AF stratified by categories of LA (p Conclusion An enlarged LA area measured by NCCT was associated with a two to four-fold higher risk of incident AF. The prognostic use of LA area provides an individual risk assessment during NCCT for other purposes. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This work was supported by the University of Southern Denmark and the Region of Southern Denmark.

Aims: The aim of the study was to identify the characteristics of the culprit lesions compared to non-culprit lesions in patients with non-ST-elevation-myocardial infarction using dual energy computed tomography (DECT). Methods and results: In 29 patients, we identified 29 culprit lesions and 227 non-culprit lesions. Quantitative values such as the effective atomic number (effective-Z) and Hounsfield Units (HU) values were measured. Furthermore, all the lesions were characterised using characteristics such as composition (non-calcified, predominantly-non-calcified, predominantly-calcified, or calcified), presence of spotty calcification, remodelling index, and napkin ring sign. The mean effective-Z and HU values were significantly lower in culprit lesions than in non-culprit lesions (8.99 ± 1.21 vs 9.79 ± 1.52; p = 0.0066 and 87.41 ± 84.97 vs. 154.45 ± 176.13; p = 0.0447). The culprit lesions had a higher frequency of non-calcified plaques and predominantly non-calcified plaques, and were with a greater presence of napkin ring signs in comparison with non-culprit lesions. There were no differences in the presence of spotty calcification or remodelling index. By adding effective-Z to plaque characteristics such as non-calcified, positive remodelling, spotty calcification, and napkin rings we observed a significant increased sensitivity of detecting culprit lesions (65.5% vs.44.8%), but no significant changes in area under curve (AUC). Conclusion: The use of DECT adds new information of the plaque composition expressed by the effective-Z, which differs significantly in culprit lesions in comparison with non-culprit lesions. The use of the effective-Z improves the diagnostic sensitivity in detection of culprit lesions.

To determine individual, expected normal diameters of the ascending aorta (AAo) and prevalence of dilations based upon an absolute cut-off point (≥ 40 mm) and individual cut-off point (≥ 25% than expected normal). Non-contrast computed tomography (CT) scans were obtained in 14,993 individuals (95.0% male, mean age 67.8 ± 3.8). A sub-group (n = 291) had AAo diameter measured by transthoracic echocardiography. A prediction formula for AAo diameters was created from multivariate linear regression analysis based upon gender, age, and body surface area. An index was made by dividing observed diameters with predicted diameters. A size-index ≥ 1.25 was defined as dilated. Prevalence of AAo dilations among males and females using 40 mm as cut-off point were 10.6% and 2.1% (p 0.001), respectively, while 3.3% and 2.6% (p = 0.305) using the size-index ≥ 1.25, respectively. Proportion of agreement between cases of AAo dilations from the size-index and 40 mm was 93.0%. Using the size-index as 'golden standard' for dilation, the sensitivity and specificity using 40 mm as cut-off point for males were 100.0% and 92.4%, respectively, while 75.0% and 99.9%, respectively, for females. For males and females, the positive predicted values were 31.3% and 93.8%, respectively; the negative predicted values were 100.0% and 99.3%, respectively. An absolute echocardiographic size-criterion of 40 mm entails a significant number of females with missed AAo dilation, and a large number of males are mistaken to have dilated AAo. Thus, AAo diameters should be evaluated in relation to gender, age and BSA. This study provides a formula for potential clinical implementation.

BACKGROUND: Due to its location very close to the bundle of His, mitral annulus calcification (MAC) might be associated with the development of atrioventricular (AV) conduction disturbances. This study assessed the association between MAC and AV conduction disturbances identified by cardiac implantable electronic device (CIED) use and electrocardiographic parameters. The association between MAC and traditional cardiovascular risk factors was also assessed.METHODS: This cross-sectional study analyzed 14,771 participants, predominantly men aged 60-75 years, from the population-based Danish Cardiovascular Screening trial. Traditional cardiovascular risk factors were obtained. Using cardiac non-contrast computed tomography imaging, MAC scores were measured using the Agatston method and divided into absent versus present and score categories. CIED implantation data were obtained from the Danish Pacemaker and Implantable Cardioverter Defibrillator Register. A 12-lead electrocardiogram was available for 2,107 participants. Associations between MAC scores and AV conduction disturbances were assessed using multivariate regression analyses.RESULTS: MAC was present in 22.4% of the study subjects. Participants with pacemakers for an AV conduction disturbance had significantly higher MAC scores (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.01-1.23) than participants without a CIED, whereas participants with a CIED for other reasons did not. Prolonged QRS-interval was significantly associated with the presence of MAC (OR, 1.45; 95% CI, 1.04-2.04), whereas prolonged PQ-interval was not. Female sex and most traditional cardiovascular risk factors were significantly associated with high MAC scores.CONCLUSIONS: MAC was associated with AV conduction disturbances, which could improve our understanding of the development of AV conduction disturbances.

Background Coronary artery calcium is important in cardiovascular risk stratification, but this knowledge is based on studies with a significant selection bias. This study aims to evaluate the external validity of a screening programme including coronary artery calcium examination, and the association between coronary artery calcium and cardiovascular events. Design Multi-centre population based study. Methods Randomly selected middle-aged men and women ( N = 1751) free of cardiovascular disease were invited to the examination during 2009–2010. Participation rate in the examination was 70%. Participants ( n = 1227) and non-participants ( n = 524) were compared regarding: cardiovascular medical treatment, Charlson comorbidity index and socioeconomic status (evaluated by cohabitation, gross income and education). Study endpoints were cardiovascular events and mortality. Results Non-participants had a significant higher comorbidity ( p = 0.003) and a lower socioeconomic status ( p Conclusions Non-participants had a higher comorbidity index and a lower socioeconomic status, but the cardiovascular event and mortality rates were equal to those of participants. Thus, a screening programme including a coronary artery calcium examination had a high external validity regarding cardiovascular risk, but also a significant social imbalance.

Aims Uric acid (UA) has been associated with the presence and severity of coronary artery disease. To further assess the role of UA role in coronary artery disease, we investigated UA levels in both healthy asymptomatic middle-aged individuals and in different subgroups of hospitalized patients with suspected or definite myocardial infarction (MI). Patients and methods The severity of coronary artery calcification (CAC) was examined in asymptomatic individuals (n=1039) using a noncontrast computed tomography scan. Hospitalized patients with suspected acute MI (n=772) were grouped according to troponin I (TnI) concentrations: (i) elevated TnI concentrations (>0.03 μg/l) with subdivision according to the type of MI and other clinical conditions associated with myocardial injury, or (ii) nonelevated TnI concentrations (=0.03 μg/l). Results UA was not associated with the severity of CAC in asymptomatic individuals when adjusting for relevant risk factors. Patients with type 2 MI and patients with myocardial injury associated with conditions of myocardial ischemia showed significantly higher UA levels (0.390 mmol/l, P=0.002 and 0.400 mmol/l, P=0.001, respectively) than patients with type 1 MI (0.329 mmol/l), after adjusting for other risk factors. Conclusion UA was not correlated with the severity of CAC in asymptomatic middle-aged individuals, and patients with type 2 MI or ischemic myocardial injury were shown to have higher UA levels than type 1 MI patients. This observation is concordant with the hypothesis that UA might be involved in the pathophysiological mechanisms leading to an imbalance in the oxygen supply/demand ratio in type 2 MI and ischemic myocardial injury.

Objectives: Abnormal glucose tolerance in patients with acute myocardial infarction (AMI) is associated with greater mortality and adverse cardiovascular effects. As statins possess a range of beneficial pleiotropic effects on the cardiovascular system, we sought to assess the cardioprotective effects of statins on left ventricular function in patients with AMI in relation to glycometabolic state. Methods: In a prospective, randomized trial, 140 patients with AMI were randomized to intensive statin therapy receiving statin loading with 80 mg of rosuvastatin followed by 40 mg daily or standard statin therapy. Patients were assessed with an oral glucose tolerance test and their left ventricular (LV) function was assessed with speckle-tracking echocardiography measuring regional longitudinal systolic strain (RLSS) in the infarct area. Results: Overall RLSS in the infarct area improved by a mean (±SD) of -4.22% (±5.19) in the intensive-care group and -2.48% (±4.01) in the usual-care group after 1 month (p = 0.047). In patients with abnormal glucose tolerance, RLSS improved by -5.01% (±5.28) in the intensive-care group and -2.15% (±4.22) in the usual-care group (p = 0.01). Conclusions: Early high-dose statin treatment improved RLSS in the infarct area in patients with AMI, and a trend of greater improvement was seen in patients with abnormal glucose tolerance.

Aims To investigate the motion correction algorithm Snapshot-Freeze (SSF) compared to standard reconstruction (STD) in patients randomized to receive beta-blockers (BB) or no beta-blockers (non-BB) before coronary CT, and to investigate if SSF can replace BB. Methods One hundred and forty patients scheduled for coronary CT were randomized. All images were reconstructed by the SSF and STD algorithms. Image quality was evaluated according to Likert score (1: excellent, 2: good, 3: adequate, 4: non-diagnostic) and presence of artifacts was noted. Results Images from 64 patients in the BB group (mean HR 56 ± 4 bpm) and 51 patients in the non-BB group (mean HR 67 ± 7 bpm) were analyzed. Twenty five patients were excluded because of tachycardia, bradycardia or reconstruction errors in SSF. SSF increased the number of excellent images in both groups compared to the STD algorithm (BB: 59% vs.44%; non-BB: 25% vs. 8%), but the number of non-diagnostic images was not significantly reduced. SSF reduced motion artifacts (BB: 11% vs. 31%; non-BB: 49% vs. 75%), but despite this reduction, motion artifacts in non-BB were still more frequent compared to the BB group analyzed by STD (49% vs. 31%). Conclusion SSF improves image quality and reduces motion artifacts, but does not compensate for the absence of BB.

To determine the potential of a non-invasive acoustic device (CADScor®System) to reclassify patients with intermediate pre-test probability (PTP) and clinically suspected stable coronary artery disease (CAD) into a low probability group thereby ruling out significant CAD. Audio recordings and clinical data from three studies were collected in a single database. In all studies, patients with a coronary CT angiography indicating CAD were referred to coronary angiography. Audio recordings of heart sounds were processed to construct a CAD-score. PTP was calculated using the updated Diamond-Forrester score and patients were classified according to the current ESC guidelines for stable CAD: low 85% PTP. Intermediate PTP patients were re-classified to low probability if the CAD-score was ≤ 20. Of 2245 patients, 212 (9.4%) had significant CAD confirmed by coronary angiography ( ≥ 50% diameter stenosis). The average CAD-score was higher in patients with significant CAD (38.4 ± 13.9) compared to the remaining patients (25.1 ± 13.8; p