Five-Year Outcomes of the Danish Cardiovascular Screening (DANCAVAS) Trial.

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.).

User-defined outcomes of the Danish cardiovascular screening (DANCAVAS) trial: A post hoc analyses of a population-based, randomised controlled trial.

BACKGROUND: The Danish cardiovascular screening (DANCAVAS) trial, a nationwide trial designed to investigate the impact of cardiovascular screening in men, did not decrease all-cause mortality, an outcome decided by the investigators. However, the target group may have varied preferences. In this study, we aimed to evaluate whether men aged 65 to 74 years requested a CT-based cardiovascular screening examination and to assess its impact on outcomes determined by their preferences. METHODS AND FINDINGS: This is a post hoc study of the randomised DANCAVAS trial. All men 65 to 74 years of age residing in specific areas of Denmark were randomised (1:2) to invitation-to-screening (16,736 men, of which 10,471 underwent screening) or usual-care (29,790 men). The examination included among others a non-contrast CT scan (to assess the coronary artery calcium score and aortic aneurysms). Positive findings prompted preventive treatment with atorvastatin, aspirin, and surveillance/surgical evaluation. The usual-care group remained unaware of the trial and the assignments. The user-defined outcome was based on patient preferences and determined through a survey sent in January 2023 to a random sample of 9,095 men from the target group, with a 68.0% response rate (6,182 respondents). Safety outcomes included severe bleeding and mortality within 30 days after cardiovascular surgery. Analyses were performed on an intention-to-screen basis. Prevention of stroke and myocardial infarction was the primary motivation for participating in the screening examination. After a median follow-up of 6.4 years, 1,800 of 16,736 men (10.8%) in the invited-to-screening group and 3,420 of 29,790 (11.5%) in the usual-care group experienced an event (hazard ratio (HR), 0.93 (95% confidence interval (CI), 0.88 to 0.98; p = 0.010); number needed to invite at 6 years, 148 (95% CI, 80 to 986)). A total of 324 men (1.9%) in the invited-to-screening group and 491 (1.7%) in the usual-care group had an intracranial bleeding (HR, 1.17; 95% CI, 1.02 to 1.35; p = 0.029). Additionally, 994 (5.9%) in the invited-to-screening group and 1,722 (5.8%) in the usual-care group experienced severe gastrointestinal bleeding (HR, 1.02; 95% CI, 0.95 to 1.11; p = 0.583). No differences were found in mortality after cardiovascular surgery. The primary limitation of the study is that exclusive enrolment of men aged 65 to 74 renders the findings non-generalisable to women or men of other age groups. CONCLUSION: In this comprehensive population-based cardiovascular screening and intervention program, we observed a reduction in the user-defined outcome, stroke and myocardial infarction, but entail a small increased risk of intracranial bleeding. TRIAL REGISTRATION: ISRCTN Registry number, ISRCTN12157806 https://www.isrctn.com/ISRCTN12157806.

ProtecT-2-D trial protocol: cardiovascular protection in patients with type 2 diabetes and established heart and/or vascular disease at a cardio-metabolic clinic-a randomized controlled trial.

BACKGROUND: Cardiovascular disease remains the primary cause of morbidity and mortality despite advancements in the treatment of patients with type 2 diabetes. Effective diabetes management extends beyond blood glucose control and includes cardiovascular prevention and treatment. However, the conventional healthcare model often emphasizes single-disease-specific management, leading to fragmented care. We aim to establish an affordable Cardio-Metabolic Clinic (CMC) that can provide comprehensive assessment and specialized care with a focus on cardiovascular protection. METHODS: The ProtecT-2-D study is a prospective, randomized control trial at the Cardiovascular Research Unit, Odense University Hospital Svendborg, Denmark. In this study, 1500 participants with type 2 diabetes and cardiovascular disease will be randomly assigned in a 2:1 ratio to receive either the intervention: treatment in the CMC, or the control: standard of care. The Cardio-Metabolic Clinic applies a decision-making algorithm coded with the latest guidelines to evaluate lifestyle factors and manage medical treatment. Health examinations are conducted at baseline and after three years, and clinical events will be assessed through registry and journal audits after five and ten years. The primary outcome is the time to the first occurrence of a composite of cardiovascular deaths, non-fatal acute myocardial infarctions, non-fatal stroke, or hospitalization due to heart failure at a time frame of five years. DISCUSSION: The Cardio-Metabolic Clinic represents a pioneering approach to diabetes management that aims to improve patient outcomes by reducing the cardiovascular disease burden. This study could transform diabetes care and offer a multidisciplinary, cost-effective, and specialized treatment. We need to establish the efficacy and feasibility of a CMC to integrate comparable clinics into broader healthcare systems, and potentially enhance cardiovascular health in patients with type 2 diabetes. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT06203860.

Statistical Analysis Plan for the AIRCARD Study: Individual Long-Term Air and Noise Pollution Exposure and Cardiovascular Disease Incidence and Mortality - A Prospective Cohort Study Utilizing DANCAVAS and VIVA Screening Trials.

INTRODUCTION: The AIRCARD study is designed to investigate the relationship between long-term exposure to air and noise pollution and cardiovascular disease incidence and mortality. We aim to conduct a robust prospective cohort analysis assessing the cumulative and differential impacts of air and noise pollution exposure on cardiovascular disease and mortality. This study will adjust for relevant confounders, including traditional cardiovascular risk factors, socioeconomic indicators, and lipid-lowering agents. METHODS: This prospective cohort study will include 27,022 male participants aged 65-74, recruited from the two large Danish DANCAVAS and VIVA trials, both population-based randomized, multicentered, clinically controlled studies. We will assess long-term exposure to air pollutants using the state-of-the-art DEHM/UBM/AirGIS modeling system and noise pollution through the Nord2000 and SoundPLAN models, covering data from 1979 to 2019. This statistical analysis plan is strictly formulated to predefine the analytical approach for all outcomes and key study variables before data access. The primary analysis will utilize Cox proportional hazards models, adjusted for confounders identified in our cohort (age, body mass index, hypertension, diabetes, smoking status, family history of heart disease, socioeconomic factors, and lipid-lowering agents). This statistical analysis plan further includes Spearman rank correlation to explore inter-pollutant associations. CONCLUSION: The AIRCARD study addresses global concerns about the impact of air and noise pollution on cardiovascular disease. This research is important for understanding how the pollutants contribute to cardiovascular disease. We aim to provide insights into this area, emphasizing the need for public health measures to mitigate pollution exposure. Our goal is to provide policymakers and healthcare professionals with information on the role of environmental factors in cardiovascular health that could influence global strategies to reduce the cardiovascular disease burden associated with pollution. The design of this SAP ensures transparency and verifiability, considering the complexities of evaluating environmental health impacts over an extended period.

Vitamin K2 and D in Patients With Aortic Valve Calcification: A Randomized Double-Blinded Clinical Trial.

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 cm2 (95% CI, -0.09 to 0.12 cm2; 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.

Liraglutide treatment is associated with progression of coronary artery fibrous plaque: a prospective 1-year follow-up study in asymptomatic patients with type 2 diabetes.

OBJECTIVE: The objective of this study was to assess the association between clinically indicated liraglutide treatment and coronary artery plaque progression during 1-year follow-up in asymptomatic diabetes. METHODS: Patients were divided into a group receiving liraglutide (Lira+) and a group not receiving liraglutide (Lira-). Coronary computed tomography angiography (CCTA) was performed to assess total atheroma volume (TAV) and subtypes of plaque volumes (dense calcium, fibrous, fibrous-fatty, and necrotic core plaque) and the plaque progression during one year follow-up. RESULTS: Fifty-five patients (27%) receiving liraglutide and 149 (73%) how did not were included. Changes in TAV during 1-year of follow-up were similar in the two groups (38 ± 180 (Lira+) vs. -1 ± 160 mm3 (Lira-), P = 0.13). A greater increase in fibrous plaque volume was seen in the Lira + vs. the Lira- group (34 ± 129 vs. -2 ± 101 mm3, P = 0.04). Changes over 1-year in the other plaque subtypes were similar in the two groups. Treatment duration of liraglutide was not associated with changes in TAV. CONCLUSION: In patients with T2D without known prior coronary artery disease, liraglutide treatment was associated with a significant increase in coronary artery fibrous plaque volume during 1-year follow-up.

The association between diabetes and abdominal aortic aneurysms in men: results of two Danish screening studies, a systematic review, and a meta-analysis of population-based screening studies.

BACKGROUND: A paradoxical protective effect of diabetes on the development and progression of abdominal aortic aneurysms (AAA) has been known for years. This study aimed to investigate whether the protective role of diabetes on AAAs has evolved over the years. METHODS: A cross-sectional study, a systematic review and meta-analysis. This study was based on two large, population-based, randomised screening trials of men aged 65-74; VIVA (2008-2011) and DANCAVAS (2014-2018), including measurement of the abdominal aorta by ultrasound or CT, respectively. Analyses were performed using multiple logistic regressions to estimate the odds ratios (ORs) for AAAs in men with diabetes compared to those not having diabetes. Moreover, a systematic review and meta-analysis of population-based screening studies of AAAs to visualise a potential change of the association between diabetes and AAAs. Studies reporting only on women or Asian populations were excluded. RESULTS: In VIVA, the prevalence of AAA was 3.3%, crude OR for AAA in men with diabetes 1.04 (95% confidence interval, CI, 0.80-1.34), and adjusted OR 0.64 (CI 0.48-0.84). In DANCAVAS, the prevalence of AAA was 4.2%, crude OR 1.44 (CI 1.11-1.87), and adjusted OR 0.78 (CI 0.59-1.04). Twenty-three studies were identified for the meta-analysis (N = 224 766). The overall crude OR was 0.90 (CI 0.77-1.05) before 2000 and 1.16 (CI 1.03-1.30) after 1999. The overall adjusted OR was 0.63 (CI 0.59-0.69) before 2000 and 0.69 (CI 0.57-0.84) after 1999. CONCLUSION: Both the crude and adjusted OR showed a statistically non-significant trend towards an increased risk of AAA by the presence of diabetes. If this represents an actual trend, it could be due to a change in the diabetes population. TRIAL REGISTRATION: DANCAVAS: Current Controlled Trials: ISRCTN12157806. VIVA: ClinicalTrials.gov NCT00662480.

Cost effectiveness of population screening vs. no screening for cardiovascular disease: the Danish Cardiovascular Screening trial (DANCAVAS).

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.

Dual-energy CT plaque characteristics of post mortem thin-cap fibroatheroma in comparison to infarct-related culprit lesions.

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.

High-risk coronary artery plaque in asymptomatic patients with type 2 diabetes: clinical risk factors and coronary artery calcium score.

BACKGROUND: High-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). METHODS: Asymptomatic 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. RESULTS: In 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 < 0.01), tobacco exposure in pack years (OR 1.02, 95% CI 1.00-1.03; p = 0.03), and glycated hemoglobin (HbA1c) (OR 1.04, 95% CI 1.02-1.07; p < 0.01) were independent predictors of HRP. No relationship was found to other risk factors. HRP was not associated with increased CACS, and 13 (23%) patients with zero CACS had at least one HRP. CONCLUSION: A 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 registration This trial was retrospectively registered at clinical trials.gov January 11, 2017 trial identifier NCT03016910.

Relation between Accumulated Air Pollution Exposure and Sub-Clinical Cardiovascular Disease in 33,723 Danish 60-74-Year-Old Males from the Background Population (AIR-CARD): A Method Article.

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.

Functional and Anatomical Testing in Intermediate Risk Chest Pain Patients with a High Coronary Calcium Score: Rationale and Design of the FACC Study.

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.

Image quality in coronary computed tomography angiography: influence of adaptive statistical iterative reconstruction at various radiation dose levels.

Background Computed tomography (CT) technology is rapidly evolving and software solution developed to optimize image quality and/or lower radiation dose. Purpose To investigate the influence of adaptive statistical iterative reconstruction (ASIR) at different radiation doses in coronary CT angiography (CCTA) in detailed image quality. Material and Methods A total of 160 CCTA were reconstructed as follows: 55 scans with filtered back projection (FBP) (650 mA), 51 scans (455 mA) with 30% ASIR (ASIR30), and 54 scans (295 mA) with 60% ASIR (ASIR60). For each reconstruction, subjective image quality was assessed by five independent certified cardiologists using a visual grading analysis (VGA) with five predefined image quality criteria consisting of a 5-point scale. Objective measures were contrast, noise, and contrast-to-noise ratio (CNR). Results The CTDIvol resulted in 10.3 mGy, 7.4 mGy, and 4.6 mGy for FBP, ASIR30, and ASIR60, respectively. Homogeneity of the left ventricular lumen was the sole aspect in which reconstruction algorithms differed with a decreasing effect for ASIR60 compared to FBP (estimated odds ratio [OR] = 0.49 [95% confidence interval (CI) = 0.32-0.76; P = 0.001]). Decreased sharpness and spatial- and low-contrast resolutions were observed when using ASIR instead of FBP, but differences were not statistically significant. Concerning objective measurements, noise increased significantly for ASIR30 (OR = 1.08; 95% CI = 1.02-1.14; P = 0.006) and ASIR60 (OR = 1.06; 95% CI = 1.01-1.12; P = 0.034) compared to FBP. Conclusion ASIR significantly decreased the subjectively assessed homogeneity of the left ventricular lumen and increased the objectively measured noise compared to FBP. Considering these results, ASIR at a reduced radiation dose should be implemented with caution.

Prognostic assessment of stable coronary artery disease as determined by coronary computed tomography angiography: a Danish multicentre cohort study.

Aims: To examine the 3.5 year prognosis of stable coronary artery disease (CAD) as assessed by coronary computed tomography angiography (CCTA) in real-world clinical practice, overall and within subgroups of patients according to age, sex, and comorbidity. Methods and results: This cohort study included 16,949 patients (median age 57 years; 57% women) with new-onset symptoms suggestive of CAD, who underwent CCTA between January 2008 and December 2012. The endpoint was a composite of late coronary revascularization procedure >90 days after CCTA, myocardial infarction, and all-cause death. The Kaplan-Meier estimator was used to compute 91 day to 3.5 year risk according to the CAD severity. Comparisons between patients with and without CAD were based on Cox-regression adjusted for age, sex, comorbidity, cardiovascular risk factors, concomitant cardiac medications, and post-CCTA treatment within 90 days. The composite endpoint occurred in 486 patients. Risk of the composite endpoint was 1.5% for patients without CAD, 6.8% for obstructive CAD, and 15% for three-vessel/left main disease. Compared with patients without CAD, higher relative risk of the composite endpoint was observed for non-obstructive CAD [hazard ratio (HR): 1.28; 95% confidence interval (CI): 1.01-1.63], obstructive one-vessel CAD (HR: 1.83; 95% CI: 1.37-2.44), two-vessel CAD (HR: 2.97; 95% CI: 2.09-4.22), and three-vessel/left main CAD (HR: 4.41; 95% CI :2.90-6.69). The results were consistent in strata of age, sex, and comorbidity. Conclusion: Coronary artery disease determined by CCTA in real-world practice predicts the 3.5 year composite risk of late revascularization, myocardial infarction, and all-cause death across different groups of age, sex, or comorbidity burden.

Association Between Diverticular Disease and Abdominal Aortic Aneurysms: Pooled Analysis of Two Population Based Screening Cohorts.

BACKGROUND: The aetiology of abdominal aortic aneurysms (AAA) is multifactorial, and many risk factors are shared with diverticular disease. It is unknown whether an independent association exists between these conditions. METHODS: Individuals enrolled in two Danish population based randomised AAA screening trials and assigned to cross sectional screening and evaluation of cardiovascular risk factors were identified. Diagnoses of diverticular disease were interrogated from a national patient registry covering the period from 1977 to the screening date. Adjusted odds ratios (aOR) and hazard ratios (aHR) with 95% CI were calculated as risk measures. RESULTS: 24,632 individuals (median age, 69 years) were included. At screening, 687 patients had pre-existing diverticular disease. Patients with diverticular disease were more likely to have AAA at screening compared with those without diverticular disease (5.2% vs. 3.3%) (OR 1.61, 95% CI 1.14-2.27). This association persisted after adjusting for potential confounders (aOR 1.49, 95% CI 1.04-2.12) and on sensitivity analyses. The association was most pronounced for those with a diagnosis of diverticular disease for at least 10 years (aOR 2.56, 95% CI 1.49-4.38). Following screening, 6.2% of patients with diverticular disease and AAA experienced aneurysm rupture, compared with 2.2% of patients with AAA without diverticular disease (aHR 4.1, 95% CI 1.6-10.8). CONCLUSION: An association was found between diverticular disease and AAA in a large population based cohort. Biological causality remains to be established, and a potential impact of diverticular disease on the natural history of AAA needs to be explored further.

Effects of Intensive Statin Therapy on Left Ventricular Function in Patients with Myocardial Infarction and Abnormal Glucose Tolerance.

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.

Lack of association between cystatin C and different coronary atherosclerotic manifestations.

Cystatin C (CysC) is known to be related to cardiovascular disease (CVD), including the presence and severity of coronary artery disease (CAD) and future clinical events. In this study, the association between CysC levels and (1) coronary artery calcification (CAC) in asymptomatic individuals from the general population as well as (2) different subgroups of patients with suspected or definite acute myocardial infarction (MI) was investigated. CysC levels were measured in serum from asymptomatic individuals as part of a screening study for CAC using non-contrast cardiac CT scan (N = 1039) as well as in subgroups of hospitalized patients with a suspected MI (N = 769). CysC was not associated with CAC in asymptomatic individuals after adjusting for relevant risk factors. No difference in CysC levels was observed between patients with type 1 MI (1.07 mg/L) and patients with normal troponin (with or without prior CAD: 1.14 and 1.01 mg/L, respectively). However, patients with type 2 MI and patient subgroups with elevated troponin but without MI had significantly higher CysC levels (1.24, 1.23 and 1.31 mg/L), even after adjusting for other risk factors. CysC was not associated with CAC in middle-aged asymptomatic individuals from the general population. Furthermore, CysC levels were found to be significantly lower in patients with type 1 MI compared to patients with type 2 MI and patients with elevated troponins but without MI. Thus, in two independent and clinically different populations, no association between CysC and coronary atherosclerotic manifestations could be demonstrated.

Artificial Intelligence-Enabled Quantitative Coronary Plaque and Hemodynamic Analysis for Predicting Acute Coronary Syndrome.

BACKGROUND: A lesion-level risk prediction for acute coronary syndrome (ACS) needs better characterization. OBJECTIVES: This study sought to investigate the additive value of artificial intelligence-enabled quantitative coronary plaque and hemodynamic analysis (AI-QCPHA). METHODS: Among ACS patients who underwent coronary computed tomography angiography (CTA) from 1 month to 3 years before the ACS event, culprit and nonculprit lesions on coronary CTA were adjudicated based on invasive coronary angiography. The primary endpoint was the predictability of the risk models for ACS culprit lesions. The reference model included the Coronary Artery Disease Reporting and Data System, a standardized classification for stenosis severity, and high-risk plaque, defined as lesions with ≥2 adverse plaque characteristics. The new prediction model was the reference model plus AI-QCPHA features, selected by hierarchical clustering and information gain in the derivation cohort. The model performance was assessed in the validation cohort. RESULTS: Among 351 patients (age: 65.9 ± 11.7 years) with 2,088 nonculprit and 363 culprit lesions, the median interval from coronary CTA to ACS event was 375 days (Q1-Q3: 95-645 days), and 223 patients (63.5%) presented with myocardial infarction. In the derivation cohort (n = 243), the best AI-QCPHA features were fractional flow reserve across the lesion, plaque burden, total plaque volume, low-attenuation plaque volume, and averaged percent total myocardial blood flow. The addition of AI-QCPHA features showed higher predictability than the reference model in the validation cohort (n = 108) (AUC: 0.84 vs 0.78; P < 0.001). The additive value of AI-QCPHA features was consistent across different timepoints from coronary CTA. CONCLUSIONS: AI-enabled plaque and hemodynamic quantification enhanced the predictability for ACS culprit lesions over the conventional coronary CTA analysis. (Exploring the Mechanism of Plaque Rupture in Acute Coronary Syndrome Using Coronary Computed Tomography Angiography and Computational Fluid Dynamics II [EMERALD-II]; NCT03591328).

COMBINING HI-RESOLUTION SCAN MODE WITH DEEP LEARNING RECONSTRUCTION ALGORITHMS IN CARDIAC CT.

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.

Can prediabetes diagnosed using HemoglobinA1c or oral glucose tolerance test predict presence and severity of coronary artery disease in symptomatic patients?

We investigated whether prediabetes diagnosed by hemoglobinA1c (HbA1c) or oral glucose tolerance test (OGTT) could predict presence and severity of coronary artery disease (CAD) in symptomatic patients. The presence of plaque, stenosis, plaque characteristics, and coronary artery calcium (CAC) were evaluated by coronary CT angiography in 702 patients with suspicion of CAD. Patients were classified by glycemic status using the American Diabetes Association criteria for HbA1c and OGTT, and compared to their respective normal ranges. Prediabetes was observed in 24% by HbA1c and 72% by OGTT. Both prediabetes classifications were associated with increased presence of plaque, stenosis, calcified plaques, CAC >400, and a lower frequency of zero CAC compared to their respective normal range (all, p < 0.05). After adjusting for potential confounders, patients with HbA1c-prediabetes had an odds ratio of 2.1 (95% CI: 1.3-3.5) for CAC >400 and 1.5 (95% CI: 1.0-2.4) for plaque presence, while none of the associations for OGTT-prediabetes were significant. The receiver operating characteristic-curve for HbA1c-prediabetes showed an area under the curve of 0.81 for CAC >400 and 0.77 for plaque presence. Prediabetes defined by HbA1c predicts presence and severity of CAD. Although OGTT identified more patients with prediabetes, their risk of CAD were not explained by prediabetes using these diagnostic-criteria.