Search

Abstract Background Coronary computed tomography angiography has become the foremost noninvasive imaging modality of the coronary arteries and is used as an alternative to the reference standard, conventional coronary angiography, for direct visualization and detection of coronary artery stenoses in patients with suspected coronary artery disease. Nevertheless, there is considerable debate regarding the optimal target population to maximize clinical performance and patient benefit. The most obvious indication for noninvasive coronary computed tomography angiography in patients with suspected coronary artery disease would be to reliably exclude significant stenosis and, thus, avoid unnecessary invasive conventional coronary angiography. To do this, a test should have, at clinically appropriate pretest likelihoods, minimal false-negative outcomes resulting in a high negative predictive value. However, little is known about the influence of patient characteristics on the clinical predictive values of coronary computed tomography angiography. Previous regular systematic reviews and meta-analyses had to rely on limited summary patient cohort data offered by primary studies. Performing an individual patient data meta-analysis will enable a much more detailed and powerful analysis and thus increase representativeness and generalizability of the results. The individual patient data meta-analysis is registered with the PROSPERO database (CoMe-CCT, CRD42012002780). Methods/Design The analysis will include individual patient data from published and unpublished prospective diagnostic accuracy studies comparing coronary computed tomography angiography with conventional coronary angiography. These studies will be identified performing a systematic search in several electronic databases. Corresponding authors will be contacted and asked to provide obligatory and additional data. Risk factors, previous test results and symptoms of individual patients will be used to estimate the pretest likelihood of coronary artery disease. A bivariate random-effects model will be used to calculate pooled mean negative and positive predictive values as well as sensitivity and specificity. The primary outcome of interest will be positive and negative predictive values of coronary computed tomography angiography for the presence of coronary artery disease as a function of pretest likelihood of coronary artery disease, analyzed by meta-regression. As a secondary endpoint, factors that may influence the diagnostic performance and clinical value of computed tomography, such as heart rate and body mass index of patients, number of detector rows, and administration of beta blockade and nitroglycerin, will be investigated by integrating them as further covariates into the bivariate random-effects model. Discussion This collaborative individual patient data meta-analysis should provide answers to the pivotal question of which patients benefit most from noninvasive coronary computed tomography angiography and thus help to adequately select the right patients for this test.

Abstract Background Fibulin-1 is one of a few extracellular matrix proteins present in blood in high concentrations. We aimed to define the relationship between plasma fibulin-1 levels and risk markers of cardiovascular disease. Methods Plasma fibulin-1 was determined in subjects with chronic kidney disease (n = 32; median age 62.5, inter-quartile range 51 – 73 years) and 60 age-matched control subjects. Among kidney disease patients serological biomarkers related to cardiovascular disease (fibrinogen, interleukin 6, C-reactive protein) were measured. Arterial applanation tonometry was used to determine central hemodynamic and arterial stiffness indices. Results We observed a positive correlation of fibulin-1 levels with age (r = 0.38; p = 0.033), glycated hemoglobin (r = 0.80; p = 0.003), creatinine (r = 0.35; p = 0.045), and fibrinogen (r = 0.39; p = 0.027). Glomerular filtration rate and fibulin-1 were inversely correlated (r = −0.57; p = 0.022). There was a positive correlation between fibulin-1 and central pulse pressure (r = 0.44; p = 0.011) and central augmentation pressure (r = 0.55; p = 0.001). In a multivariable regression model, diabetes, creatinine, fibrinogen and central augmentation pressure were independent predictors of plasma fibulin-1. Conclusion Increased plasma fibulin-1 levels were associated with diabetes and impaired kidney function. Furthermore, fibulin-1 levels were associated with hemodynamic cardiovascular risk markers. Fibulin-1 is a candidate in the pathogenesis of cardiovascular disease observed in chronic kidney disease and diabetes.

The prevalence of transient myocardial ischaemia after myocardial infarction seems to be lower than in other subgroups with coronary artery disease. In postinfarction patients, however, a greater proportion of ischaemic episodes are silent. At present there is substantial evidence that transient ischaemia provides prognostic information in different subsets of patients with previous myocardial infarction, but there is considerable disagreement about how this is expressed in terms of cardiac events. Small patient numbers, patient selection, and different timing of ambulatory monitoring are proposed as important reasons for the inconsistent findings. The precise role of ambulatory ST segment monitoring in clinical practice has yet to be established. Direct comparisons with exercise stress testing may not be appropriate for two reasons. Firstly, the main advantage of ambulatory monitoring may be that it can be performed early after infarction at the time of maximum risk. Secondly, it can be performed in most patients after infarction, including those recognised as being at high risk who are unable to perform an exercise stress test. [ABSTRACT FROM PUBLISHER]

This study evaluated the potential consequences of the redefined joint European/American electrocardiographic criteria for an established myocardial infarction (MI). New and previous diagnostic Q-wave criteria were used in patients with stable angina pectoris. Seventy-nine patients with and 77 patients without a documented previous MI were compared using the results of myocardial perfusion imaging at rest as a reference. With the new Q-wave criteria, 71% of the former group and 40% of the latter had evidence of established MI compared with 33% and 3% when using the previous criteria (p <0.0001). Sensitivity, specificity, and positive and negative predictive values were 71%, 60%, 64%, and 67% for the new criteria versus 33%, 97%, 93%, and 59% with the previous criteria. These data suggest that that the new Q-wave criteria may be too nonspecific, resulting in an inappropriately high number of false-positive results. [ABSTRACT FROM AUTHOR]

Background: The prognostic impact of complete coronary revascularization relative to non-invasive testing methods is unknown., Objectives: To assess the association between completeness of revascularization defined by CTA-derived fractional flow reserve (FFR CT ) and cardiovascular outcomes in patients with stable angina., Methods: Multicenter 3-year follow-up study of patients with new onset stable angina and ≥ 30% stenosis by CTA. The lesion-specific FFR CT value (two cm-distal-to-stenosis) was registered in all vessels with stenosis and considered abnormal when ≤ 0.80. Patients with FFR CT ≤ 0.80 were categorized as: Completely revascularized (CR-FFR CT ), all vessels with FFR CT ≤ 0.80 revascularized; incompletely revascularized (IR-FFR CT ), ≥ 1 vessels with FFR CT ≤ 0.80 non-revascularized. Early revascularization (< 90 days from index CTA) categorized vessels as revascularized. The primary endpoint comprised cardiovascular death and non-fatal myocardial infarction; the secondary endpoint vessel-specific late revascularization and non-fatal myocardial infarction., Results: Amongst 900 patients and 1759 vessels, FFR CT was ≤ 0.80 in 377 (42%) patients, 536 (30%) vessels; revascularization was performed in 244 (27%) patients, 340 (19%) vessels. Risk of the primary endpoint was higher for IR-FFR CT (15/210 [7.1%]) compared to CR-FFR CT (4/167 [2.4%]), RR: 2.98; 95% CI: 1.01-8.8, p ​= ​0.036, and to normal FFR CT (3/523 [0.6%]), RR: 12.45; 95% CI: 3.6-42.6, p ​< ​0.001. Incidence of the secondary endpoint was higher in non-revascularized vessels with FFR CT ≤ 0.80 (29/250 [12%]) compared to revascularized vessels with FFR CT ≤ 0.80 (5/286 [1.7%]), p ​= ​0.001, and to vessels with FFR CT > 0.80 (10/1223 [0.8%]), p ​< ​0.001., Conclusion: Incomplete revascularization of patients with lesion-specific FFR CT ≤ 0.80 is associated to unfavorable cardiovascular outcomes compared to those with complete revascularization or FFR CT > 0.80., Competing Interests: Declaration of competing interest CR is a full-time employee of HeartFlow, and receives salary and stock options from HeartFlow. ELG has no conflicts related to this manuscript but has received speaker honoraria or consultancy fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Lundbeck Pharma, Novo Nordisk and Organon. He is investigator in clinical studies sponsored by AstraZeneca, Idorsia or Bayer and has received unrestricted research grants from Boehringer Ingelheim. JL is a consultant and holds stock options in Circle CVI and HeartFlow. KN acknowledges support from the NIH and reports unrestricted institutional research support from Siemens Healthineers, Bayer, HeartFlow Inc and Novartis. MP has received research grants from Janssen, Bayer, Heartflow and NIH and is part of the following advisory boards: Janssen, Bayer, Heartflow, Phillips. SM is a full-time employee of HeartFlow, and shareholder of HeartFlow. TF is associated with the HeartFlow speakers bureau. All other authors had no disclosures to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The association between coronary computed tomography angiography (CTA) derived fractional flow reserve (FFR CT ) and risk of recurrent angina in patients with new onset stable angina pectoris (SAP) and stenosis by CTA is uncertain., Methods: Multicenter 3-year follow-up study of patients presenting with symptoms suggestive of new onset SAP who underwent first-line CTA evaluation and subsequent standard-of-care treatment. All patients had at least one ≥30 ​% coronary stenosis. A per-patient lowest FFR CT -value ≤0.80 represented an abnormal test result. Patients with FFR CT ≤0.80 who underwent revascularization were categorized according to completeness of revascularization: 1) Completely revascularized (CR-FFR CT ), all vessels with FFR CT ≤0.80 revascularized; or 2) incompletely revascularized (IR-FFR CT ) ≥1 vessels with FFR CT ≤0.80 non-revascularized. Recurrent angina was evaluated using the Seattle Angina Questionnaire., Results: Amongst 769 patients (619 [80 ​%] stenosis ≥50 ​%, 510 [66 ​%] FFR CT ≤0.80), 174 (23 ​%) reported recurrent angina at follow-up. An FFR CT ≤0.80 vs ​> ​0.80 associated to increased risk of recurrent angina, relative risk (RR): 1.82; 95 ​% CI: 1.31-2.52, p ​< ​0.001. Risk of recurrent angina in CR-FFR CT (n ​= ​135) was similar to patients with FFR CT >0.80, 13 ​% vs 15 ​%, RR: 0.93; 95 ​% CI: 0.62-1.40, p ​= ​0.72, while IR-FFR CT (n ​= ​90) and non-revascularized patients with FFR CT ≤0.80 (n ​= ​285) had increased risk, 37 ​% vs 15 ​% RR: 2.50; 95 ​% CI: 1.68-3.73, p ​< ​0.001 and 30 ​% vs 15 ​%, RR: 2.03; 95 ​% CI: 1.44-2.87, p ​< ​0.001, respectively. Use of antianginal medication was similar across study groups., Conclusion: In patients with SAP and coronary stenosis by CTA undergoing standard-of-care guided treatment, FFR CT provides information regarding risk of recurrent angina., Competing Interests: Declaration of competing interest CR is a full-time employee of HeartFlow, and receives salary and stock options from HeartFlow. ELG has no conflicts related to this manuscript but has received speaker honoraria or consultancy fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, MSD, Lundbeck Pharma and Organon. He is investigator in clinical studies sponsored by AstraZeneca or Bayer and has received unrestricted research grants from Boehringer Ingelheim. JL is a consultant and holds stock options in Circle CVI and HeartFlow. KN acknowledges support from the NIH and reports unrestricted institutional research support from Siemens Healthineers, Bayer, HeartFlow Inc and Novartis. MP has received research grants from Janssen, Bayer, Heartflow and NIH and is part of the following advisory boards: Janssen, Bayer, Heartflow, Phillips. SM is a full-time employee of HeartFlow, and shareholder of HeartFlow. TF is associated with the HeartFlow speakers bureau. All other authors had no disclosures to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Coronary computed tomography angiography (CCTA) has higher diagnostic accuracy than coronary artery calcium (CAC) score for detecting obstructive coronary artery disease (CAD) in patients with stable chest pain, while the added diagnostic value of combining CCTA with CAC is unknown. We investigated whether combining coronary CCTA with CAC score can improve the diagnosis of obstructive CAD compared with CCTA alone., Methods: A total of 2315 patients (858 women, 37%) aged 61.1 ± 10.2 from 29 original studies were included to build two CAD prediction models based on either CCTA alone or CCTA combined with the CAC score. CAD was defined as at least 50% coronary diameter stenosis on invasive coronary angiography. Models were built by using generalized linear mixed-effects models with a random intercept set for the original study. The two CAD prediction models were compared by the likelihood ratio test, while their diagnostic performance was compared using the area under the receiver-operating-characteristic curve (AUC). Net benefit (benefit of true positive versus harm of false positive) was assessed by decision curve analysis., Results: CAD prevalence was 43.5% (1007/2315). Combining CCTA with CAC improved CAD diagnosis compared with CCTA alone (AUC: 87% [95% CI: 86 to 89%] vs. 80% [95% CI: 78 to 82%]; p < 0.001), likelihood ratio test 236.3, df: 1, p < 0.001, showing a higher net benefit across almost all threshold probabilities., Conclusion: Adding the CAC score to CCTA findings in patients with stable chest pain improves the diagnostic performance in detecting CAD and the net benefit compared with CCTA alone., Clinical Relevance Statement: CAC scoring CT performed before coronary CTA and included in the diagnostic model can improve obstructive CAD diagnosis, especially when CCTA is non-diagnostic., Key Points: • The combination of coronary artery calcium with coronary computed tomography angiography showed significantly higher AUC (87%, 95% confidence interval [CI]: 86 to 89%) for diagnosis of coronary artery disease compared to coronary computed tomography angiography alone (80%, 95% CI: 78 to 82%, p < 0.001). • Diagnostic improvement was mostly seen in patients with non-diagnostic C. • The improvement in diagnostic performance and the net benefit was consistent across age groups, chest pain types, and genders., (© 2023. The Author(s).)

Background The prognostic value of coronary CT angiography (CTA)-derived fractional flow reserve (FFR) beyond 1-year outcomes and in patients with high levels of coronary artery calcium (CAC) is uncertain. Purpose To assess the prognostic value of coronary CTA-derived FFR test results on 3-year clinical outcomes in patients with coronary stenosis and among a subgroup of patients with high levels of CAC. Materials and Methods This study represents a 3-year follow-up of patients with new-onset stable angina pectoris who were consecutively enrolled in the Assessing Diagnostic Value of Noninvasive CT-FFR in Coronary Care, known as ADVANCE (ClinicalTrials.gov: NCT02499679) registry, between December 2015 and October 2017 at three Danish sites. A high CAC was defined as an Agatston score of at least 400. A lesion-specific coronary CTA-derived FFR value of 2 cm with distal-to-stenosis value at or below 0.80 represented an abnormal test result. The primary end point was a composite of all-cause death and nonfatal spontaneous myocardial infarction. Event rates were estimated using the one-sample binomial model, and relative risk was compared between participants stratified by results of coronary CTA-derived FFR. Results This study included 900 participants: 523 participants with normal results (mean age, 64 years ± 9.6 [SD]; 318 male participants) and 377 with abnormal results from coronary CTA-derived FFR (mean age, 65 years ± 9.6; 264 male participants). The primary end point occurred in 11 of 523 (2.1%) and 25 of 377 (6.6%) participants with normal and abnormal coronary CTA-derived FFR results, respectively (relative risk, 3.1; 95% CI: 1.6, 6.3; P < .001). In participants with high CAC, the primary end point occurred in four of 182 (2.2%) and 19 of 212 (9.0%) participants with normal and abnormal coronary CTA-derived FFR results, respectively (relative risk, 4.1; 95% CI: 1.4, 11.8; P = .001). Conclusion In individuals with stable angina, a normal coronary CTA-derived FFR test result identified participants with a low 3-year risk of all-cause death or nonfatal spontaneous myocardial infarction, both in the overall cohort and in participants with high CAC scores. Clinical trial registration no. NCT02499679 Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Sinitsyn in this issue.

Introduction: Coronary artery calcification (CAC) and especially progression in CAC is a strong predictor of acute myocardial infarction and cardiovascular mortality. Supplementation with vitamin K2 and D3 has been suggested to have a protective role in the progression of CAC. In this study, we will examine the effect of vitamins K2 and D3 in men and women with severe CAC. We hypothesise that supplementation with vitamins K2 and D3 will slow down the calcification process., Method and Analysis: In this multicentre and double-blinded placebo-controlled study, 400 men and women with CAC score≥400 are randomised (1:1) to treatment with vitamin K2 (720 µg/day) and vitamin D3 (25 µg/day) or placebo treatment (no active treatment) for 2 years. Among exclusion criteria are treatment with vitamin K antagonist, coagulation disorders and prior coronary artery disease. To evaluate progression in coronary plaque, a cardiac CT-scan is performed at baseline and repeated after 12 and 24 months of follow-up. Primary outcome is progression in CAC score from baseline to follow-up at 2 years. Among secondary outcomes are coronary plaque composition and cardiac events. Intention-to-treat principle is used for all analyses., Ethics and Dissemination: There are so far no reported adverse effects associated with the use of vitamin K2. The protocol was approved by the Regional Scientific Ethical Committee for Southern Denmark and the Data Protection Agency. It will be conducted in accordance with the Declaration of Helsinki. Positive as well as negative findings will be reported., Trial Registration Number: NCT05500443., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Chronic kidney disease (CKD) is a global challenge. CKD prevalence estimation is central to management strategies and prevention. It is necessary to predict end stage kidney disease (ESKD) and, subsequently, the burden for healthcare systems. In this study we characterize CKD stage 3-5 prevalence and incidence in a cohort covering the majority of the Region of Southern Denmark and investigate individuals' demographic, socioeconomic, and comorbidity status., Methods: We used data from the Kidney Disease Cohort (KidDiCo) combining laboratory data from Southern Denmark with Danish national databases. Chronic kidney disease was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines., Results: The prevalence varied between 4.83 and 4.98% and incidence rate of CKD was 0.49%/year. The median age was 76.4 years. The proportion of individuals with CKD stage 3-5 in the entire population increased consistently with age. The percentage of women in the CKD 3-5 group was higher than in the background population. Diabetes mellitus, hypertension and cardiovascular disease were more prominent in patients with CKD. CKD stage 5 and ESKD were more frequent as incident CKD stages in the 18-49 year olds when compared to older individuals. CKD patients tended to have a lower socioeconomic status., Conclusion: Chronic kidney disease stage 3-5 is common, especially in the elderly. Patients with CKD stage 3-5 are predominantly female. The KidDiCo data suggests an association between lower socioeconomic status and prevalence of CKD., (© 2023. The Author(s).)

Chronic kidney disease (CKD) is a known risk factor for cardiovascular disease, including acute myocardial infarction. However, whether this risk is only associated with severe kidney disease or is also related to mildly impaired kidney function is still under debate. The incidence rate and risk factors of incident acute myocardial infarction (AMI) in patients with CKD are sparse. Potential differences in risk factor profiles between CKD patients with incident AMI and CKD patients with a prior AMI have not been sufficiently investigated. Furthermore, important factors such as albuminuria and socio-economic factors are often not included. The primary aim of this study was to establish the incidence rate of AMI after CKD debut. Secondly, to evaluate the importance of different CKD stages and the risk of having an AMI. Finally, to identify individuals at risk for AMI after CKD debut adjusted for prevalent AMI. Based on data from the kidney disease cohort of Southern Denmark (KidDiCo), including 66,486 CKD patients, we established incidence rates and characteristics of incident AMI among patients within a 5-year follow-up period after CKD debut. A Cox regression was performed to compute the cause-specific hazard ratios for the different risk factors. The incidence rate for CKD stage G3−5 patients suffering acute myocardial infarction is 2.5 cases/1000 people/year. In patients without a previous myocardial infarction, the risk of suffering a myocardial infarction after CKD debut was only significant in CKD stage G4 (HR = 1.402; (95% CI: 1.08−1.81); p-value = 0.010) and stage G5 (HR = 1.491; (95% CI: 1.01−2.19); p-value = 0.042). This was not the case in patients who had suffered an acute myocardial infarction prior to their CKD debut. In this group, a previous myocardial infarction was the most critical risk factor for an additional myocardial infarction after CKD debut (HR = 2.615; (95% CI: 2.241−3.05); p-value < 0.001). Irrespective of a previous myocardial infarction, age, male sex, hypertension, and a low educational level were significant risk factors associated with an acute myocardial infarction after CKD debut. The incidence rate of AMI in patients with CKD stage G3−5 was 2.5 cases/1000 people/year. Risk factors associated with incident AMI in CKD stage G3−5 patients were CKD stage, age, and hypertension. Female sex and higher educational levels were associated with a lower risk for AMI. Prior AMI was the most significant risk factor in patients with and without previous AMI before fulfilling CKD stage G3−5 criteria. Only age, sex, and a medium-long educational level were significant risk factors in this group.

Objectives: There is conflicting evidence about the comparative diagnostic accuracy of the Agatston score versus computed tomography angiography (CTA) in patients with suspected obstructive coronary artery disease (CAD)., Purpose: To determine whether CTA is superior to the Agatston score in the diagnosis of CAD., Methods: In total 2452 patients with stable chest pain and a clinical indication for invasive coronary angiography (ICA) for suspected CAD were included by the Collaborative Meta-analysis of Cardiac CT (COME-CCT) Consortium. An Agatston score of > 400 was considered positive, and obstructive CAD defined as at least 50% coronary diameter stenosis on ICA was used as the reference standard., Results: Obstructive CAD was diagnosed in 44.9% of patients (1100/2452). The median Agatston score was 74. Diagnostic accuracy of CTA for the detection of obstructive CAD (81.1%, 95% confidence interval [CI]: 77.5 to 84.1%) was significantly higher than that of the Agatston score (68.8%, 95% CI: 64.2 to 73.1%, p < 0.001). Among patients with an Agatston score of zero, 17% (101/600) had obstructive CAD. Diagnostic accuracy of CTA was not significantly different in patients with low to intermediate (1 to < 100, 100-400) versus moderate to high Agatston scores (401-1000, > 1000)., Conclusions: Results in our international cohort show CTA to have significantly higher diagnostic accuracy than the Agatston score in patients with stable chest pain, suspected CAD, and a clinical indication for ICA. Diagnostic performance of CTA is not affected by a higher Agatston score while an Agatston score of zero does not reliably exclude obstructive CAD., Key Points: • CTA showed significantly higher diagnostic accuracy (81.1%, 95% confidence interval [CI]: 77.5 to 84.1%) for diagnosis of coronary artery disease when compared to the Agatston score (68.8%, 95% CI: 64.2 to 73.1%, p < 0.001). • Diagnostic performance of CTA was not affected by increased amount of calcium and was not significantly different in patients with low to intermediate (1 to <100, 100-400) versus moderate to high Agatston scores (401-1000, > 1000). • Seventeen percent of patients with an Agatston score of zero showed obstructive coronary artery disease by invasive angiography showing absence of coronary artery calcium cannot reliably exclude coronary artery disease., (© 2022. The Author(s).)

Background: Data on the referral rate of chronic kidney disease (CKD) patients to specialists are sparse. Investigating referral rates and characterizing patients with kidney disease not followed by a nephrologist are relevant for future measures in order to optimize public health and guideline implementation., Methods: Data were extracted from the Kidney Disease Cohort of Southern Denmark (KidDiCo). Referral rates for all incident CKD patients below 60 mL/min/1.73 m² and referral rates according to the KDIGO guidelines based on glomerular filtration rates below 30 mL/min/1.73 m² were calculated. Information on contact with one of the nephrologist outpatient clinics in the Region of Southern Denmark was collected from the Danish National Patient Registry. The individual follow-up time for nephrology contact was 12 months. Additional data were accessed via the respective national databases. CKD patients on dialysis and kidney transplanted patients were excluded., Results: A total of 3% of patients with an eGFR <60 mL/min/1.73 m²-16% of patients with an eGFR <30 mL/min/1.73 m² and 35% of patients with an eGFR <15 mL/min/1.73 m² were in contact with a nephrologist in the outpatient settings. Younger age, male sex, diabetes, hypertension, higher education and proximity to a nephrology outpatient clinic increased the chance of nephrology follow-up., Conclusion: Only a small fraction of CKD patients are followed by a nephrologist. More studies should be performed in order to find out which patients will profit the most from renal referral and how to optimize the collaboration between nephrologists and general practitioners., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Background: The influence of extensive coronary calcifications on the diagnostic and prognostic value of coronary computed tomography angiography-derived fractional flow reserve (FFR CT ) has been scantily investigated., Objectives: The purpose of this study was to investigate the diagnostic and short-term role of FFR CT in chest pain patients with Agatston score (AS) >399., Methods: This was a prospective multicenter study of 260 stable patients with suspected coronary artery disease (CAD) and AS >399. FFR CT was measured blinded by an independent core laboratory. All patients underwent invasive coronary angiography (ICA) and FFR if indicated. The agreement of FFR CT  ≤0.80 with hemodynamically significant CAD on ICA/FFR (≥50% left main or ≥70% epicardial artery stenosis and/or FFR ≤0.80) was assessed. Patients undergoing FFR had colocation FFR CT measured, and the lowest per-patient FFR CT was registered in all patients. The association among per-patient FFR CT , coronary revascularization, and major clinical events (all-cause mortality, myocardial infarction, or unstable angina hospitalization) at 90-day follow-up was evaluated., Results: Median age and AS were 68.5 years (IQR: 63-74 years) and 895 (IQR: 587-1,513), respectively. FFR CT was ≤0.80 in 204 patients (78%). Colocation FFR CT (n = 112) showed diagnostic accuracy, sensitivity, and specificity to identify hemodynamically significant CAD of 71%, 87%, and 54%. The area under the receiver-operating characteristics curve (AUC) was 0.75. When using the lowest FFR CT (n = 260), per-patient accuracy, sensitivity, and specificity were 57%, 95%, and 32%, respectively. The AUC was 0.84. A total of 85 patients underwent revascularization, and FFR CT was ≤0.80 in 96% of these. During follow-up, major clinical events occurred in 3 patients (1.2%), all with FFR CT  ≤0.80., Conclusions: Most patients with AS >399 had FFR CT  ≤0.80. Using ICA/FFR as the reference revealed a moderate diagnostic accuracy of colocation FFR CT . Compared with the lowest per-patient FFR CT , colocation FFR CT measurement improved diagnostic accuracy and specificity. The 90-day follow-up was favorable with few coronary revascularizations and no major clinical events occurring in patients with FFR CT >0.80. (Use of FFR-CT in Stable Intermediate Chest Pain Patients With Severe Coronary Calcium Score [FACC]; NCT03548753)., Competing Interests: Funding Support and Author Disclosures This investigator-initiated study was fully funded by grants from The Region of Southern Denmark (Departments of Cardiology at the Odense University Hospital and Esbjerg Hospital). FFR(CT) analyses were performed per fee by Heart Flow Inc. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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 <0.001)., 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.

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., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Identifying acute myocardial infarction in patients with renal disease is notoriously difficult, due to atypical presentation and chronically elevated troponin. The aim of this study was to identify a specific troponin T/troponin I cut-off value for diagnosis of acute myocardial infarction in patients with renal impairment via meta-analysis. Two investigators screened 2590 publications from MEDLINE, Embase, PubMed, Web of Science, and the Cochrane library. Only studies that investigated alternative cut-offs according to renal impairment were included. Fifteen articles fulfilled the inclusion criteria. Six studies were combined for meta-analysis. The manufacturer's upper reference level for troponin T is 14 ng/L. Based on the meta-analyses, cut-off values for troponin in patients with renal impairment with myocardial infarction was 42 ng/L for troponin I and 48 ng/L for troponin T. For patients on dialysis the troponin T cut-off is even higher at 239 ng/L. A troponin I cut-off value for dialysis patients could not be established due to lack of data. The 15 studies analyzed showed considerable diversity in study design, study population, and the definition of myocardial infarction. Further studies are needed to define a reliable troponin cut-off value for patients with kidney disease, especially in dialysis patients, and to allow necessary subanalysis.

Aims: To evaluate and compare survival after out-of-hospital (OHCA), where an automated external defibrillator (AED) was used, in densely, moderately and thinly populated areas. Also, to evaluate the association between AED retrieval distance and survival after OHCA., Methods: From 2014 to 2018, AEDs used during OHCA in the region of Southern Denmark were systematically collected. OHCAs were included if the OHCA address was known. OHCAs at nursing homes were excluded. To evaluate population density, a map with 1000 × 1000 meter grid cells was used with each cell color-graded according to the number of inhabitants. Densely, moderately and thinly populated areas were defined as ≥200 inhabitants, 20-199 inhabitants and 0-19 inhabitants per km 2 , respectively. Primary outcome was 30-day survival., Results: A total of 423 cases of OHCA were included, of which 207 (49%) occurred in densely populated areas, while 78 (18%) and 138 (33%) occurred in moderately and thinly populated areas, respectively. AED retrieval distances were: densely populated 105 m (IQR 5-450), moderately populated 220 m (IQR 5-450) and thinly populated 350 m (IQR 5-1500) (P < 0.001). Thirty-day survival was 40%, 31% and 34%, respectively (P = 0.3). In a multivariable regression analysis, mortality increased with 10% per 100 m an AED was placed further away from the site of OHCA., Conclusion: Survival after OHCA, where an AED was used, did not seem to differ in thinly, moderately and densely populated areas. The length of the AED retrieval distance, however, was correlated with reduced survival after adjusting for other potentially explanatory variables., Competing Interests: Declaration of Competing Interest Doctor Møller has received grants and personal fees from Abiomed, and personal fees from Orion Pharma and Novartis. All other authors declared no conflict of interests., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: 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 <50% coronary stenoses were identified. Information on post-CTA use of statin therapy and cardiovascular events were obtained from national registries., 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., Competing Interests: Funding Support and Author Disclosures This work was supported by a research grant to Dr Øvrehus by the Faculty of Health Sciences, University of Southern Denmark. Dr Grove has received speaker honoraria or consultancy fees from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Pfizer, Merck Sharp & Dohme, MundiPharma, Portola Pharmaceuticals, and Roche; and an unrestricted research grant from Boehringer Ingelheim. Dr Nørgaard has received unrestricted institutional research grants from Siemens and Heart Flow. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021. Published by Elsevier Inc.)

Aims: To evaluate 1) the relative use of automated external defibrillators (AEDs) at different types of AED locations 2) the percentage of AEDs crossing location types during OHCA before use 3) the AED coverage distance at different types of AED locations, and 4) the 30-day-survival in different subgroups., Methods: From 2014-2018, AEDs used by bystanders during out-of-hospital cardiac arrest (OHCA) in the Region of Southern Denmark were collected. Data regarding registered AEDs was retrieved from the national AED-network. The OHCA site and AED placement was categorized into; 1) Residential; 2) Public; 3) Nursing home, 4) Company/workplace; 5) Institution; 6) Health clinic and 7) Sports facility/recreational. To evaluate 30-day-survival, groups 4-7 were pooled into one Mixed group., Results: In total 509 OHCAs were included. There was high relative usage of AEDs from public places, nursing homes, health clinics and sports facilities, and low relative usage from companies/workplaces, residential areas and institutions. Of AEDs used during residential OHCAs 39% were collected from public places. AEDs placed in residential areas and public places had a coverage of 575 m (IQR 130-1300) and 270 m (IQR5-550), respectively. Thirty-day- survival in public, residential and mixed groups were 49%, 14% and 67%, respectively., Conclusion: The relative use of AEDs from public places, nursing homes, sports facilities and health clinics was high, and AEDs used during OHCA in residential areas were most frequently collected from public places. AEDs placed in both residential areas and public places may have a wider coverage area than proposed in current literature., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background and Aims: Vitamin K antagonists (VKA) remain the most frequently prescribed oral anticoagulants worldwide despite the introduction of non-vitamin K antagonist oral anticoagulants (NOAC). VKA interfere with the regeneration of Vitamin K1 and K2, essential to the activation of coagulation factors and activation of matrix-Gla protein, a strong inhibitor of arterial calcifications. This study aimed to clarify whether VKA treatment was associated with the extent of coronary artery calcification (CAC) in a population with no prior cardiovascular disease (CVD)., Methods: We collected data on cardiovascular risk factors and CAC scores from cardiac CT scans performed as part of clinical examinations (n = 9,672) or research studies (n = 14,166) in the period 2007-2017. Data on use of anticoagulation were obtained from the Danish National Health Service Prescription Database. The association between duration of anticoagulation and categorized CAC score (0, 1-99, 100-399, ≥400) was investigated by ordered logistic regression adjusting for covariates., Results: The final study population consisted of 17,254 participants with no prior CVD, of whom 1,748 and 1,144 had been treated with VKA or NOAC, respectively. A longer duration of VKA treatment was associated with higher CAC categories. For each year of VKA treatment, the odds of being in a higher CAC category increased (odds ratio (OR) = 1.032, 95%CI 1.009-1.057). In contrast, NOAC treatment duration was not associated with CAC category (OR = 1.002, 95%CI 0.935-1.074). There was no significant interaction between VKA treatment duration and age on CAC category., Conclusions: Adjusted for cardiovascular risk factors, VKA treatment-contrary to NOAC-was associated to higher CAC category., Competing Interests: The authors have declared that no competing interests exist.

Objective: To prospectively validate the CT-Valve score, a new risk score designed to identify patients with valvular heart disease at a low risk of coronary artery disease (CAD) who could benefit from multislice CT (MSCT) first instead of coronary angiography (CAG)., Methods: This was a prospective cohort study of patients referred for valve surgery in the Capital Region of Denmark and Odense University Hospital from the 1 February 2015 to the 1 February 2017. MSCT was implemented for patients with a CT-Valve score ≤7 at the referring physician's discretion. Patients with a history of CAD or chronic kidney disease were excluded. The primary outcome was the proportion of patients needing reevaluation with CAG after MSCT and risk of CAD among the patients determined to be low to intermediate risk., Results: In total, 1149 patients were included. The median score was 9 (IQR 3) and 339 (30%) had a score ≤7. MSCT was used for 117 patients. Of these 29 (25%) were reevaluated and 9 (7.7%) had CAD. Of the 222 patients with a score ≤7 that did not receive an MSCT, 14 (6%) had significant CAD. The estimated total cost of evaluation among patients with a score ≤7 before implementation was €132 093 compared with €79 073 after, a 40% reduction. Similarly, estimated total radiation before and after was 608 mSv and 362 mSv, a 41% reduction. Follow-up at a median of 32 months (18-48) showed no ischaemic events for patients receiving only MSCT., Conclusion: The CT-Valve score is a valid method for determining risk of CAD among patients with valvular heart disease. Using a score ≤7 as a cut-off for the use of MSCT is safe and cost-effective., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: To evaluate response rates for volunteer first responders (VFRs) activated by use of a smartphone GPS-tracking system and to compare response times of VFRs with those of emergency medical services (EMS). Furthermore, to evaluate 30-day-survival after out-of-hospital cardiac arrest (OHCA) on a rural island., Methods: Since 2012 a GPS-tracking system has been used on a rural island to activate VFRs during all emergency calls requesting an EMS. When activated, three VFRs were recruited and given distinct roles, including collection of the nearest automatic external defibrillator (AED). We retrospectively investigated EMS response data from April 2012 to December 2017. These were matched with VFR response times from the GPS-tracking system. The 30-day survival in OHCA patients was also assessed., Results: In 2266 of 2662 emergency calls (85%) at least one VFR arrived to the site before EMS. Median response times for VFRs (n = 2662) was 4:46 min:sec (IQR 3:16-6:52) compared with 10:13 min:sec (6:14-13:41) for EMS (p < 0.0001). A total of 17 OHCAs took place in public locations and 65 in residential areas. Thirty-day survival in these were 24% and 15%, respectively., Conclusion: Use of a smartphone GPS-tracking system to dispatch VFRs ensures that in more than four of five cases, a VFR arrives to the site before EMS. Response times for VFRs were also found to be lower than EMS response times. Finally, the 30-day survival of OHCA patients in a rural area, based on these results, surpass our expectations., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: Coronary artery disease (CAD) is frequent in patients with newly diagnosed heart failure (HF). Multislice CT (MSCT) is a non-invasive alternative to coronary angiography (CAG) suggested for patients with a low-to-intermediate risk of CAD. No established definition of such patients exists. Our purpose was to develop a simple score to identify as large a group as possible with a suitable pretest risk of CAD., Methods: Retrospective study of patients in Denmark undergoing CAG due to newly diagnosed HF from 2010 to 2014. All Danish patients were registered in two databases according to geographical location. We used data from one registry and multiple logistic regression with backwards elimination to find predictors of CAD and used the derived OR to develop a clinical risk score called the CT-HF score, which was subsequently validated in the other database., Results: The main cohort consisted of 2171 patients and the validation cohort consisted of 2795 patients with 24% and 27% of patients having significant CAD, respectively. Among significant predictor, the strongest was extracardiac arteriopathy (OR 2.84). Other significant factors were male sex, smoking, hyperlipidaemia, diabetes mellitus, angina and age. A proposed cut-off of 9 points identified 61% of patients with a 15% risk of having CAD, resulting in an estimated savings of 15% of the cost and 21% of the radiation., Conclusions: A simple score based on clinical risk factors could identify HF patients with a low risk of CAD; these patients may have benefitted from MSCT as a gatekeeper for CAG., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (© 2019 S. Karger AG, Basel.)

Combined myocardial flow reserve (MFR) by PET and CT coronary angiography (CTA) is a promising tool for assessment of coronary artery disease. Prior analyses of MFR/CTA has been performed as side-by-side interpretation, not as volume rendered, full hybrid analysis, with fused MFR/CTA. We aimed to: (i) establish a method for full hybrid analysis of MFR/CTA, (ii) validate the inter- and intra-observer reproducibility of MFR values, and (iii) determine the diagnostic value of side-by-side versus full hybrid MFR/CTA with 15-O-water PET. Forty-four outpatients scheduled for invasive coronary angiography (ICA) were enrolled prospectively. All underwent rest/stress 15-O-water PET/CTA with ICA as reference. Within two observers of different experience, the Pearson r at global and territorial level exceeded 0.953 for rest, stress, and MFR values, as determined by Carimas software. Within and between observers, the mean differences between rest, stress, and MFR values were close to zero and the confidence intervals for 95% limits of agreement were narrow. The diagnostic performance of full hybrid PET/CTA did not outperform the side-by-side approach, but performed better than MFR without CTA at vessel level: specificity 93% (95% confidence limits: 89-97%) versus 76% (64-88%), p = 0.0004; positive predictive value 71% (55-86%) versus 51% (37-65%), p = 0.0001; accuracy 90% (84-95%) versus 77% (69-84%), p = 0.0009. MFR showed high reproducibility within and between observers of different experience. The full hybrid model was not superior to side-by-side interpretation of MFR/CTA, but proved better than MFR alone at vessel level with regard to specificity, positive predictive value, and accuracy.

The original version of this article, published on 19 March 2018, unfortunately contained a mistake. The following correction has therefore been made in the original: The names of the authors Philipp A. Kaufmann, Ronny Ralf Buechel and Bernhard A. Herzog were presented incorrectly.

Objectives: To analyse the implementation, applicability and accuracy of the pretest probability calculation provided by NICE clinical guideline 95 for decision making about imaging in patients with chest pain of recent onset., Methods: The definitions for pretest probability calculation in the original Duke clinical score and the NICE guideline were compared. We also calculated the agreement and disagreement in pretest probability and the resulting imaging and management groups based on individual patient data from the Collaborative Meta-Analysis of Cardiac CT (CoMe-CCT)., Results: 4,673 individual patient data from the CoMe-CCT Consortium were analysed. Major differences in definitions in the Duke clinical score and NICE guideline were found for the predictors age and number of risk factors. Pretest probability calculation using guideline criteria was only possible for 30.8 % (1,439/4,673) of patients despite availability of all required data due to ambiguity in guideline definitions for risk factors and age groups. Agreement regarding patient management groups was found in only 70 % (366/523) of patients in whom pretest probability calculation was possible according to both models., Conclusions: Our results suggest that pretest probability calculation for clinical decision making about cardiac imaging as implemented in the NICE clinical guideline for patients has relevant limitations., Key Points: • Duke clinical score is not implemented correctly in NICE guideline 95. • Pretest probability assessment in NICE guideline 95 is impossible for most patients. • Improved clinical decision making requires accurate pretest probability calculation. • These refinements are essential for appropriate use of cardiac CT.

Introduction: Aortic stenosis is a common heart valve disease, and due to the growing elderly population, the prevalence is increasing. The disease is progressive with increasing calcification of the valve cusps. A few attempts with medical preventive treatment have failed; thus, presently, the only effective treatment of aortic stenosis is surgery. This study will examine the effect of menaquinone-7 (MK-7) supplementation on progression of aortic valve calcification (AVC). We hypothesise that MK-7 supplementation will slow down the calcification process., Methods and Analysis: In this multicenter and double-blinded, placebo-controlled study, 400 men aged 65-74 years with substantial AVC are randomised (1:1) to treatment with MK-7 (720 µg/day) supplemented by the recommended daily dose of vitamin D (25 µg/day) or placebo treatment (no active treatment) for 2 years. Exclusion criteria are treatment with vitamin K antagonist or coagulation disorders. To evaluate AVC score, a non-contrast CT scan is performed at baseline and repeated after 12 and 24 months of follow-up. Primary outcome is difference in AVC score from baseline to follow-up at 2 years. Intention-to-treat principle is used for all analyses., Ethics and Dissemination: There are no reported adverse effects associated with the use of MK-7. The protocol is approved by the Regional Scientific Ethical Committee for Southern Denmark (S-20170059) and the Data Protection Agency (17/19010). It is conducted in accordance with the Declaration of Helsinki. Positive as well as negative findings will be reported., Trial Registration Number: NCT03243890., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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 < 0.0001), while cardiovascular medical treatment was alike. Over a median follow-up time of 6.5 years the cardiovascular event and mortality rates were equal (6.7% vs. 6.4%, p = 0.80 and 0.4% vs. 0.5%, p = 0.76, respectively). Adjusted hazard ratio was 0.90 (95% confidence interval (CI) 0.63-1.37). Among participants, the extent of coronary artery calcium was significantly associated with increased risk of cardiovascular events (hazard ratio 1.92, 95% CI 1.03-3.54, hazard ratio 3.66, 95% CI 1.82-7.32, hazard ratio 6.51, 95% CI 3.17-13.36 for coronary artery calcium scores 1-99, 100-399, ≥400 AU, respectively). 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.

BACKGROUND This case study demonstrated that although highly symptomatic, agenesis of the left circumflex artery was a benign finding. Anomalies of the coronary arteries were found to be the cause of sudden death in a young individual. Left circumflex anomalies were not associated with major cardiac events. CASE REPORT A 20-year-old male was admitted due to syncope preceded by chest pain. His electrocardiogram (ECG) showed global ST segment elevation as well as biphasic T waves in anterior precordial leads. Troponin T values were normal. Echocardiography was normal. Computerized axial tomography (CAT) scan showed agenesis of the circumflex artery with a super-dominant right coronary artery. Myocardial scintigraphy showed no perfusion defects. Exercise test did not present any arrhythmias. Tilt table test displayed stable blood pressure and pulse response. A reveal recorder registered no malignant arrhythmias. A coronary angiography confirmed the finding of the CAT scan and showed no collateral vessel development. CONCLUSIONS This case demonstrated that agenesis left circumflex artery although presenting with severe symptoms, such as chest pain, is a benign finding. Chest pain was not correlated to perfusion defects in this case. Although the patient experienced loss of consciousness, there was no objective support for cardiac origin as no malignant arrhythmias were found.