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Coronary CT angiography (CTA) derived fractional flow reserve (FFR CT ) is recommended for physiological assessment in intermediate coronary stenosis for guiding referral to invasive coronary angiography (ICA). In this study, we report real-world data on the feasibility of implementing a CTA/FFR CT test algorithm as a gatekeeper to ICA at referral hospitals. Retrospective all-comer study of patients with new onset stable symptoms and suspected coronary stenosis (30-89%) by CTA. Evaluation of CTA datasets, interpretation of FFR CT analysis, and decisions on downstream testing were performed by skilled CT-cardiologists. CTA was performed in 3974 patients, of whom 381 (10%) were referred directly to ICA, whereas 463 (12%) to non-invasive functional testing: FFR CT 375 (81%) and perfusion imaging 88 (19%). FFR CT analysis was rejected in 8 (2%) due to inadequate CTA image quality. Number of patients deferred from ICA after FFR CT was 267 (71%), while 100 (27%) were referred to ICA. Obstructive coronary artery disease (CAD) was confirmed in 62 (62%) patients and revascularization performed in 53 (53%). Revascularization rates, n (%), were higher in patients undergoing FFR CT -guided versus CTA-guided referral to ICA: 30-69% stenosis, 28 (44%) versus 8 (21%); 70-89% stenosis, 39 (69%) versus 25 (46%), respectively, both p < 0.05. Implementation of FFR CT at referral hospitals was feasible, reduced the number of invasive procedures, and increased the revascularization rate., (© 2024. The Author(s).)

Aim: The SCORE2 algorithm is recommended to estimate risk of cardiovascular disease (CVD). Coronary artery calcification (CAC) score is expensive but improves the risk prediction. This study aims to determine and compare the additive value of CAC-score and 19 biomarkers in risk prediction., Methods: Traditional cardiovascular (CV) risk factors, CAC-score, and a wide range of biomarkers (including lipids, calcium-phosphate metabolism, troponin, inflammation, kidney function and ankle brachial index (ABI)) were collected from 1211 randomly selected middle-aged men and women in this multicenter prospective cohort in 2009-2010. 10-year follow-up data on CV-events were obtained via the Danish Health Registries. CV-event was defined as stroke, myocardial infarction, hospitalization for heart failure, coronary artery revascularization or death from CVD. The association between SCORE2, CAC-score, biomarkers, and CV-events was assessed using cox proportional hazard rates (HR) and compared using AUC-calculation of ROC-curves. Finally, net reclassification improvement (NRI) was calculated., Results: 92 participants had CV-events. Adjusted for risk factors, CAC-score was significantly associated with events (adjusted HR 1.9 (95%CI:1.1; 3.3), 3.6 (95%CI:1.9; 6.8), and 5. (95%CI:2.6; 10.3) for CAC-score 1-99, CAC-score 100-399 and CAC-score ≥400, respectively. HR for the highest quartile of CRP was 2.3 (95%CI:1.2; 4.5), while none of the remaining biomarkers improved HR. Adjusted for SCORE2, the CAC-score improved AUC (AUC CAC : 0.72, AUC SCORE2 : 0.67, p< 0.01). A combination of selected biomarkers (total cholesterol, low-density lipoprotein, phosphate, troponin, CRP, and creatinine) borderline improved AUC (AUC Biomarkers + SCORE2 : 0.71, AUC SCORE2 : 0.67, p= 0.06). NRI for CAC score was 63 % ( p< 0.0001)., Conclusion: CAC-score improved prediction of CV-events, however the selected biomarkers did not., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V.)

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: Some autoimmune diseases carry elevated risk for atherosclerotic cardiovascular disease (ASCVD), yet the underlying mechanism and the influence of traditional risk factors remain unclear., Objectives: This study sought to determine whether autoimmune diseases independently correlate with coronary atherosclerosis and ASCVD risk and whether traditional cardiovascular risk factors modulate the risk., Methods: The study included 85,512 patients from the Western Denmark Heart Registry undergoing coronary computed tomography angiography. A diagnosis of 1 of 18 autoimmune diseases was assessed. Adjusted OR (aOR) for any plaque, any coronary artery calcification (CAC), CAC of >90th percentile, and obstructive coronary artery disease as well as adjusted HR (aHR) for ASCVD were calculated., Results: During 5.3 years (Q1-Q3: 2.8-8.2 years) of follow-up, 3,832 ASCVD events occurred. A total of 4,064 patients had a diagnosis of autoimmune disease, which was associated with both presence of any plaque (aOR: 1.29; 95% CI: 1.20-1.40), any CAC (aOR: 1.28; 95% CI: 1.19-1.37), and severe CAC of >90th percentile (aOR: 1.53; 95% CI: 1.39-1.68), but not with having obstructive coronary artery disease (aOR: 1.04; 95% CI: 0.91-1.17). Patients with autoimmune diseases had a 46% higher risk (aHR: 1.46; 95% CI: 1.29-1.65) for ASCVD. Traditional cardiovascular risk factors were strongly associated with future ASCVD events, and a favorable cardiovascular risk factor profile in autoimmune patients was associated with ∼54% lower risk compared to patients with presence of risk factors (aHR: 0.46; 95% CI: 0.27-0.81)., Conclusions: Autoimmune diseases were independently associated with higher burden of coronary atherosclerosis and higher risk for future ASCVD events, with risk accentuated by traditional cardiovascular risk factors. These findings suggest that autoimmune diseases increase risk through accelerated atherogenesis and that cardiovascular risk factor control is key for improving prognosis in patients with autoimmune diseases., Competing Interests: Funding Support and Author Disclosures This study was funded by Aarhus University Hospital. The funding source had no influence on study design, conduct or reporting. Dr Blaha has received grants from the National Institutes of Health, U.S. Food and Drug Administration, American Heart Association, and Aetna Foundation; has received grants and personal fees from Amgen; and has received personal fees from Sanofi, Regeneron, Novartis, Bayer, and Novo Nordisk outside the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: Coronary CT angiography (CTA) derived fractional flow reserve (FFR CT ) shows high diagnostic performance when compared to invasively measured FFR. Presence and extent of low attenuation plaque density have been shown to be associated with abnormal physiology by measured FFR. Moreover, it is well established that statin therapy reduces the rate of plaque progression and results in morphology alterations underlying atherosclerosis. However, the interplay between lipid lowering treatment, plaque regression, and the coronary physiology has not previously been investigated., Aim: To test whether lipid lowering therapy is associated with significant improvement in FFR CT , and whether there is a dose-response relationship between lipid lowering intensity, plaque regression, and coronary flow recovery., Methods: Investigator driven, prospective, multicenter, randomized study of patients with stable angina, coronary stenosis ≥50% determined by clinically indicated first-line CTA, and FFR CT  ≤ 0.80 in whom coronary revascularization was deferred. Patients are randomized to standard (atorvastatin 40 mg daily) or intensive (rosuvastatin 40 mg + ezetimibe 10 mg daily) lipid lowering therapy for 18 months. Coronary CTA scans with blinded coronary plaque and FFR CT analyses will be repeated after 9 and 18 months. The primary endpoint is the 18-month difference in FFR CT using (1) the FFR CT value 2 cm distal to stenosis and (2) the lowest distal value in the vessel of interest. A total of 104 patients will be included in the study., Conclusion: The results of this study will provide novel insights into the interplay between lipid lowering, and the pathophysiology in coronary artery disease., (© 2022 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

Background: Diabetes mellitus is a major risk factor for coronary artery disease (CAD) and may provoke structural and functional changes in coronary vasculature. The coronary volume to left ventricular mass (V/M) ratio is a new anatomical parameter capable of revealing a potential physiological imbalance between coronary vasculature and myocardial mass. The aim of this study was to examine the V/M derived from coronary computed tomography angiography (CCTA) in patients with diabetes., Methods: Patients with clinically suspected CAD enrolled in the ADVANCE (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care) registry and known diabetic status were included. Coronary artery volume and left ventricular myocardial mass were analyzed from CCTA and the V/M ratio was calculated and compared between patients with and without diabetes., Results: Of the 3053 patients (age 66 ​± ​10 years; 66% male) with known diabetic status, diabetes was present in 21.9%. Coronary volume was lower in patients with diabetes compared to those without diabetes (2850 ​± ​940 ​mm 3 vs. 3040 ​± ​970 ​mm 3 , p ​< ​0.0001), whereas the myocardial mass was comparable between the 2 groups (122 ​± ​33 ​g vs. 122 ​± ​32 ​g, p ​= ​0.70). The V/M ratio was significantly lower in patients with diabetes (23.9 ​± ​6.8 ​mm 3 /g vs. 25.7 ​± ​7.5 ​mm 3 /g, p ​< ​0.0001). Among subjects with obstructive CAD (n ​= ​2191, 24.0% diabetics) and non-obstructive CAD (16.7% diabetics), the V/M ratio was significantly lower in patients with diabetes compared to those without (23.4 ​± ​6.7 ​mm 3 /g vs. 25.0 ​± ​7.3 ​mm 3 /g, p ​< ​0.0001 and 25.6 ​± ​6.9 ​mm 3 /g vs. 27.3 ​± ​7.6 ​mm 3 /g, respectively, p ​= ​0.006)., Conclusion: The V/M ratio was significantly lower in patients with diabetes compared to non-diabetics, even after correcting for obstructive coronary stenosis. The clinical value of the reduced V/M ratio in diabetic patients needs further investigation., Competing Interests: Declaration of competing interest The department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands has received unrestricted research grants from Medtronic, Biotronik, Boston Scientific, and Edwards Lifesciences. Dr. Patel has received research grants from HeartFlow, Bayer, Janssen, and the National Heart, Lung, and Blood Institute; and has served on the advisory board for HeartFlow, Bayer, and Janssen. Dr. Nørgaard has received unrestricted institutional research grants from Siemens and HeartFlow. Dr. Fairbairn has served on the Speakers Bureau for HeartFlow. Dr. Nieman has received institutional research support from Siemens Healthineers, HeartFlow, GE Healthcare, and Bayer Healthcare. Dr. Berman has received unrestricted research support from HeartFlow. Dr. Hurwitz Koweek has received research support and speaking fees from HeartFlow and Siemens. Dr. Pontone has received institutional research grant and/or honorarium as consultant/speaker from GE Healthcare, Boehringer, Bracco, Medtronic, Bayer, and HeartFlow. Dr. Sonck has received research grant support from the Cardiopath PhD program. Dr. Rabbat has served as a consultant for HeartFlow. Dr. De Bruyne has received consulting fees from Abbott, Opsens, and Boston Scientific; and is a shareholder for Siemens, GE Healthcare, Bayer, Philips, HeartFlow, Edwards Lifesciences, and Sanofi. Dr. Rogers is employee of and owns equity in HeartFlow. Dr. Leipsic has received research grants from GE Healthcare and Edwards Lifesciences; and has served as a consultant for and holds stock options in Circle Cardiovascular Imaging and HeartFlow Inc. Dr. Bax has received speaker fees from Abbot Vascular. Dr. Knuuti has received consultancy fees from GE Healthcare and AstraZeneca and speaker fees from GE Healthcare, Bayer, Lundbeck, Boehringer-Ingelheim and Merck, outside of the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The role of change in fractional flow reserve derived from CT (FFR CT ) across coronary stenoses (ΔFFR CT ) in guiding downstream testing in patients with stable coronary artery disease (CAD) is unknown., Objectives: To investigate the incremental value of ΔFFR CT in predicting early revascularization and improving efficiency of catheter laboratory utilization., Materials: Patients with CAD on coronary CT angiography (CCTA) were enrolled in an international multicenter registry. Stenosis severity was assessed as per CAD-Reporting and Data System (CAD-RADS), and lesion-specific FFR CT was measured 2 ​cm distal to stenosis. ΔFFR CT was manually measured as the difference of FFR CT across visible stenosis., Results: Of 4730 patients (66 ​± ​10 years; 34% female), 42.7% underwent ICA and 24.7% underwent early revascularization. ΔFFR CT remained an independent predictor for early revascularization (odds ratio per 0.05 increase [95% confidence interval], 1.31 [1.26-1.35]; p ​< ​0.001) after adjusting for risk factors, stenosis features, and lesion-specific FFR CT . Among the 3 models (model 1: risk factors ​+ ​stenosis type and location ​+ ​CAD-RADS; model 2: model 1 ​+ ​FFR CT ; model 3: model 2 ​+ ​ΔFFR CT ), model 3 improved discrimination compared to model 2 (area under the curve, 0.87 [0.86-0.88] vs 0.85 [0.84-0.86]; p ​< ​0.001), with the greatest incremental value for FFR CT 0.71-0.80. ΔFFR CT of 0.13 was the optimal cut-off as determined by the Youden index. In patients with CAD-RADS ≥3 and lesion-specific FFR CT ≤0.8, a diagnostic strategy incorporating ΔFFR CT >0.13, would potentially reduce ICA by 32.2% (1638-1110, p ​< ​0.001) and improve the revascularization to ICA ratio from 65.2% to 73.1%., Conclusions: ΔFFR CT improves the discrimination of patients who underwent early revascularization compared to a standard diagnostic strategy of CCTA with FFR CT , particularly for those with FFR CT 0.71-0.80. ΔFFR CT has the potential to aid decision-making for ICA referral and improve efficiency of catheter laboratory utilization., Competing Interests: Declaration of competing interest This study was supported by HeartFlow, Inc., Redwood City, California, via individual Clinical Study Agreements with each enrolling institution and with the Duke Clinical Research Institute (DCRI) for Core Laboratory activities and Clinical Event Committee adjudication of adverse events. Dr. Leipsic receives institutional grants to provide core lab services to Edwards Life Sciences, Medtronic and is a consultant to Circle CVI and HeartFlow. Dr. Fairbairn is on the Speakers Bureau for HeartFlow. Dr. Nørgaard has received unrestricted institutional research grants from Siemens and HeartFlow. Dr. Berman has received unrestricted research support from HeartFlow. Dr. Chinnaiyan has received institutional grants from HeartFlow. Dr. Hurwitz-Koweek is on the Speakers Bureau for HeartFlow; and has unrestricted grant funding from Siemens and HeartFlow. Dr. Pontone is a consultant for GE Healthcare; and has research grants from GE Healthcare and HeartFlow. Dr. Rabbat has received institutional grants from HeartFlow. Dr. Mullen is an employee of HeartFlow. Dr. Rogers is an employee of and has equity in HeartFlow. Dr. Bax has received unrestricted research grants from Edwards Lifescience, Medtronic, Boston Scientific, Biotronik, and GE Healthcare; and is on the Speakers Bureau with Abbott. Dr. Douglas receives an institutional research grant from HeartFlow. Dr. Patel has received grants from HeartFlow, Jansen, Bayer, AstraZeneca, and NHLBI; and has served as a consultant for Jansen, Bayer, AstraZeneca, Genzyme, and Merck. Dr. Nieman reports institutional research support from Siemens Healthineers, Bayer, HeartFlow Inc. and is a consultant to Siemens Medical Solutions USA. Dr. Ihdayhid is supported by the National Health and Medical Research Council of Australia and National Heart Foundation Scholarships; and has received honoraria from Canon Medical and Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to examine prevalence, predictors, and impact of coronary artery calcium (CAC) across different risk factor burdens on the prevalence of obstructive coronary artery disease (CAD) and future coronary heart disease (CHD) risk in young patients., Background: The interplay of risk factors and CAC for predicting CHD in young patients aged ≤45 years is not clear., Methods: The study included 3,691 symptomatic patients (18-45 years of age) from the WDHR (Western Denmark Heart Registry) undergoing coronary computed tomographic angiography. CHD events were myocardial infarction and late revascularization., Results: During a median of 4.1 years of follow-up, 57 first-time CHD events occurred. In total, 3,180 patients (86.1%) had CAC = 0 and 511 patients (13.9%) had CAC >0. Presence of CAC increased with number of risk factors (odds ratio: 4.5 [95% CI: 2.7-7.3] in patients with >3 vs 0 risk factors). The prevalence of obstructive CAD at baseline and the rate of future CHD events increased in a stepwise manner with both higher CAC and number of risk factors. The CHD event rate was lowest at 0.5 (95% CI: 0.1-3.6) per 1,000 person-years in patients with 0 risk factors and CAC = 0. Among patients with >3 risk factors, the event rate was 3.1 (95% CI: 1.0-9.7) in patients with CAC = 0 compared with 36.3 (95% CI: 17.3-76.1) in patients with CAC >10., Conclusions: In young patients, there is a strong interplay between CAC and risk factors for predicting the presence of obstructive CAD and for future CHD risk. In the presence of risk factors, even a low CAC score is a high-risk marker. These results demonstrate the importance of assessing risk factors and CAC simultaneously when assessing risk in young patients., Competing Interests: Funding Support and Author Disclosures This study was funded by Aarhus University Hospital. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: This study sought to investigate outcomes following a normal CT-derived fractional flow reserve (FFRCT) result in patients with moderate stenosis and coronary artery calcification, and to describe the relationship between the extent of calcification, stenosis, and FFRCT., Methods and Results: Data from 975 consecutive patients suspected of chronic coronary syndrome with stenosis (30-70%) determined by computed CT angiography and FFRCT to guide downstream management decisions were reviewed. Median (range) follow-up time was 2.2 (0.5-4.2) years. Coronary artery calcium (CAC) scores were ≥400 in 25%, stenosis ≥50% in 83%, and FFRCT >0.80 in 51% of the patients. There was a lower incidence of the composite endpoint (death, myocardial infarction, hospitalization for unstable angina, and unplanned coronary revascularization) at 4.2 years in patients with any CAC and FFRCT > 0.80 vs. FFRCT ≤ 0.80 (3.9% and 8.7%, P = 0.04), however, in patients with CAC scores ≥400 the risk difference between groups did not reach statistical significance, 4.2% vs. 9.7% (P = 0.24). A negative relationship between CAC scores and FFRCT irrespective of stenosis severity was demonstrated., Conclusion: FFRCT shows promise in identifying patients with stenosis and calcification who can be managed without further downstream testing. Moreover, an inverse relationship between CAC levels and FFRCT was demonstrated. Studies are needed to further assess the clinical utility of FFRCT in patients with extensive coronary calcification., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background: CT coronary angiography (CTA) with Fractional Flow Reserve as determined by CT (FFR CT ) is a safe alternative to invasive coronary angiography. A negative FFR CT has been shown to have low cardiac event rates compared to those with a positive FFR CT . However, the clinical utility of FFR CT according to age is not known., Methods: Patients' in the ADVANCE (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care) registry, were stratified into those ≥65 or <65 years of age. The impact of FFR CT on clinical decision-making, as assessed by patient age, was determined by evaluating patient management using CTA results alone, followed by site investigators submitting a report on the treatment plan based upon the newly provided FFR CT data. Outcomes at 1-year post CTA were assessed, including major adverse cardiovascular events (myocardial infarction, all-cause mortality or unplanned hospitalization for ACS leading to revascularisation) and total revascularisation. Positive FFR CT was deemed to be ​≤ ​0.8., Results: FFR CT was calculated in 1849 (40.6%) subjects aged <65 and 2704 (59.4%) ​≥ ​65 years of age. Subjects ≥65 years were more likely to have anatomic obstructive disease on CTA (≥50% stenosis), compared to those aged <65 (69.7% and 73.2% respectively, p ​= ​0.008). There was a similar graded increase in recommended and actual revascularisation with either CABG or PCI, with declining FFR CT strata for subjects above and below the age of 65. MACE and revascularisation rates were not significantly different for those ​≥ ​or <65, regardless of FFR CT positivity or stenosis severity <50% or ≥50%. With a negative FFR CT result, and anatomical stenosis ≥50%, those ​≥ ​and <65 years of age, had similar rates of MACE (0.2% for both, p ​= ​0.1) and revascularisation (8.7% and 10.4% respectively p ​= ​0.4). Logistic regression analysis, with age as a continuous variable, and adjustment for Diamond Forrester Risk, baseline FFR CT and treatment (CABG, PCI, medical therapy), indicated a statistically significant, but small increase in the odds of a MACE event with increasing age (OR 1.04, 95% CI 1.006-1.08, p ​= ​0.02). Amongst patients with a FFR CT > 0.80, there was no effect of age on the odds of revascularisation., Conclusion: The findings of this study point to a low risk of MACE events or need for revascularisation in those aged ​≥ ​or <65 with a FFR CT >0.80, despite the higher incidence of anatomic obstructive CAD in those ≥65 years. The findings show the clinical usefulness and outcomes of FFR CT are largely constant regardless of age., (Copyright © 2020 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Objectives: The authors sought to assess the distribution of 5-year risk of cardiovascular disease (CVD) events (myocardial infarction, revascularizations, ischemic stroke) and death among symptomatic patients with varying degrees of coronary artery disease (CAD) ascertained from computed tomography angiography (CTA)., Background: CTA is used increasingly as the first-line test for evaluating patients with symptoms suggestive of CAD. This creates the daily clinical challenge of best using the information available from CTA to guide appropriate downstream allocation of preventive treatments., Methods: Among 21,275 patients from the Western Denmark Heart Registry, the authors developed a model predicting 5-year risk for CVD and death based on traditional risk factors and CAD severity. Only events occurring >90 days after CTA were included., Results: During a median follow-up of 4.2 years, 1,295 CVD events and deaths occurred. The median 5-year risk for events was 4% (interquartile range: 3% to 8%), and ranged from <5% to >50% in individual patients. The degree of CAD severity was the strongest risk factor; however, traditional risk factors also contributed significantly to risk. Thus, risk distributions in patients with varying degree of CAD overlapped considerably, and patients with extensive nonobstructive CAD could have higher estimated risk than patients with obstructive CAD (stenosis >50%). Among patients with obstructive CAD, 12% had 5-year risk <10% whereas 24% had risk >20%. A similar large overlap in risk was found when revascularizations were excluded from the endpoint., Conclusions: The 5-year risk for CVD events and death varies substantially in symptomatic patients undergoing CTA, even in the presence of obstructive CAD. These results provide support for individual risk assessment to improve potential benefit when allocating preventive therapies following CTA., Competing Interests: Funding Support and Author Disclosures This study was funded by Aarhus University Hospital. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Patients with obstructive coronary artery disease (CAD) are at high risk for cardiovascular disease (CVD) events. However, it remains unclear whether the high risk is due to high atherosclerotic disease burden or if presence of stenosis has independent predictive value., Objectives: The purpose of this study was to evaluate if obstructive CAD provides predictive value beyond its association with total calcified atherosclerotic plaque burden as assessed by coronary artery calcium (CAC)., Methods: Among 23,759 symptomatic patients from the Western Denmark Heart Registry who underwent diagnostic computed tomography angiography (CTA), we assessed the risk of major CVD (myocardial infarction, stroke, and all-cause death) stratified by CAC burden and number of vessels with obstructive disease., Results: During a median follow-up of 4.3 years, 1,054 patients experienced a first major CVD event. The event rate increased stepwise with both higher CAC scores and number of vessels with obstructive disease (by CAC scores: 6.2 per 1,000 person-years (PY) for CAC = 0 to 42.3 per 1,000 PY for CAC >1,000; by number of vessels with obstructive disease: 6.1 per 1,000 PY for no CAD to 34.7 per 1,000 PY for 3-vessel disease). When stratified by 5 groups of CAC scores (0, 1 to 99, 100 to 399, 400 to 1,000, and >1,000), the presence of obstructive CAD was not associated with higher risk than presence of nonobstructive CAD., Conclusions: Plaque burden, not stenosis per se, is the main predictor of risk for CVD events and death. Thus, patients with a comparable calcified atherosclerosis burden generally carry a similar risk for CVD events regardless of whether they have nonobstructive or obstructive CAD., Competing Interests: Author Disclosures This study was funded by Aarhus University Hospital. Dr. Blaha has received grants from the National Institutes of Health, U.S. Food and Drug Administration, American Heart Association, and Aetna Foundation; has received grants and personal fees from Amgen; and has received personal fees from Sanofi, Regeneron, Novartis, Bayer, and NovoNordisk outside of the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: To investigate the impact of applying coronary computed tomography angiography (CCTA), as the recommended first-line diagnostic test in patients with suspected chronic coronary syndrome (CCS) on the use of invasive coronary angiography (ICA) and revascularization practice., Methods and Results: We included all patients undergoing a first-time CCTA (n = 53555) and first-time ICA (n = 41451) from 2008 to 2017 due to suspected CCS in Western Denmark (3.3 million inhabitants). The number of CCTA procedures increased from 352 (2008) to 7739 (2017) (2098%), ICA examinations declined from 4538 to 3766 (17%). The average proportion of no- or non-obstructive coronary artery disease by CCTA was 77.5%. Referral to ICA after CCTA occurred in 16.9% of patients in 2008-10 vs. 13.9% in 2014-17 (P < 0.0001). Revascularization in patients referred to ICA after CCTA increased from 33.8% in 2008-10 vs. 44.4% in 2014-17 (P < 0.0001). The revascularization proportion in patients undergoing ICA with no preceding CCTA was 32.3% in 2008-10 vs. 33.3% in (2014-17) (P = 0.1063). Stratified by age, the overall revascularization proportion increased in the younger age groups and was unchanged or decreased in older age groups: <50 years: 60% increase, 50-59 years: 33% increase, 60-69 years: 0%, and >70 years: 9.5% decrease., Conclusion: The introduction of CCTA as a first-line diagnostic test in patients with suspected CCS does not associate with increased use of invasive angiography and seems to have facilitated a more appropriate revascularization practice., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Objectives: This study is to determine the management and clinical outcomes of patients investigated with coronary computed tomography angiography (CCTA)-derived fractional flow reserve (FFR CT ) according to sex., Background: Women are underdiagnosed with conventional ischemia testing, have lower rates of obstructive coronary artery disease (CAD) at invasive coronary angiography (ICA), yet higher mortality compared to men. Whether FFR CT improves sex-based patient management decisions compared to CCTA alone is unknown., Methods: Subjects with symptoms and CAD on CCTA were enrolled (2015 to 2017). Demographics, symptom status, CCTA anatomy, coronary volume to myocardial mass ratio (V/M), lowest FFR CT values, and management plans were captured. Endpoints included reclassification rate between CCTA and FFR CT management plans, incidence of ICA demonstrating obstructive CAD (≥50% stenosis) and revascularization rates., Results: A total of 4,737 patients (n = 1,603 females, 33.8%) underwent CCTA and FFR CT . Women were older (age 68 ± 10 years vs. 65 ± 10 years; p < 0.0001) with more atypical symptoms (41.5% vs. 33.9%; p < 0.0001). Women had less obstructive CAD (65.4% vs. 74.7%; p < 0.0001) at CCTA, higher FFR CT (0.76 ± 0.10 vs. 0.73 ± 0.10; p < 0.0001), and lower likelihood of positive FFR CT ≤ 0.80 for the same degree stenosis (p < 0.0001). A positive FFR CT ≤0.80 resulted in equal referral to ICA (n = 510 [54.5%] vs. n = 1,249 [56.5%]; p = 0.31), but more nonobstructive CAD (n = 208 [32.1%] vs. n = 354 [24.5%]; p = 0.0003) and less revascularization (n = 294 [31.4%] vs. n = 800 [36.2%]; p < 0.0001) in women, unless the FFR CT was ≤0.75 where revascularization rates were similar (n = 253 [41.9%] vs. n = 715 [46.4%]; p = 0.06). Women have a higher V/M ratio (26.17 ± 7.58 mm 3 /g vs. 24.76 ± 7.22 mm 3 /g; p < 0.0001) that is associated with higher FFR CT independent of degree stenosis (p < 0.001). Predictors of revascularization included stenosis severity, FFR CT, symptoms, and V/M ratio (p < 0.001) but not female sex (p = 0.284)., Conclusions: FFR CT differs between the sexes, as women have a higher FFR CT for the same degree of stenosis. In FFR CT -positive CAD, women have less obstructive CAD at ICA and less revascularization, which is associated with higher V/M ratio. The findings suggest that CAD and FFR CT variations by sex need specific interpretation as these differences may affect therapeutic decision making and clinical outcomes. (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care [ADVANCE]; NCT02499679)., Competing Interests: Author Disclosures This study was supported by HeartFlow, Inc., Redwood City, California, via individual Clinical Study Agreements with each enrolling institution and with the Duke Clinical Research Institute (DCRI) for Core Laboratory activities and Clinical Event Committee adjudication of adverse events. Dr. Fairbairn is on the Speakers Bureau for Heartflow. Dr. Hurwitz-Koweek is on the Speakers Bureau for Heartflow; and has unrestricted grant funding from Siemens and Heartflow. Dr. Nørgaard has received unrestricted institutional research grants from Siemens and HeartFlow. Dr. Nieman has received unrestricted institutional research grants from Siemens, Bayer, GE, and HeartFlow. Dr. Bax has received unrestricted research grants from Edwards Lifescience, Medtronic, Boston Scientific, Biotronik, and GE Healthcare; and is on the Speakers Bureau with Abbott. Dr. Pontone is a consultant for GE Healthcare; and has research grants from GE Healthcare and Heartflow. Dr. Raff has received institutional grants from HeartFlow. Dr. Chinnaiyan has received institutional grants from HeartFlow. Dr. Rabbat has received institutional grants from HeartFlow. Dr. Binukrishnan is on the Speakers Bureau for Heartflow. Dr. Rogers is an employee of and has equity in Heartflow. Dr. Berman has received unrestricted research support from Heartflow. Dr. Patel has received grants from HeartFlow, Jansen, Bayer, AstraZeneca, and NHLBI; and has served as a consultant for Jansen, Bayer, AstraZeneca, Genzyme, and Merck. Dr. Douglas has received institutional grants from HeartFlow. Dr. Leipsic is a consultant for and has stock options in Circle CVI and Heartflow. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: This study aimed to assess if information on CAD severity from coronary computed tomography angiography (CTA) can identify patients that benefit most from treating low-density lipoprotein-cholesterol (LDL-C) to American Heart Association/American College of Cardiology (ACC/AHA) and European Society of Cardiology (ESC) guidelines targets., Background: Current treatment guidelines for secondary prevention of atherosclerotic cardiovascular disease (ASCVD) disregard severity of coronary artery disease (CAD) for treatment choices. It is unclear whether severity of CAD should be considered in treatment recommendations., Methods: Among 20,241 symptomatic patients undergoing diagnostic CTA from the Western Denmark Heart Registry, we assessed the number needed to treat (NNT) in 6 years to prevent 1 ASCVD event as well as the proportion of all events that could be prevented by treating LDL-C to targets. We assumed a 22% relative reduction of ASCVD events per 1 mmol/l reduction in LDL-C., Results: In multivariable analysis with no CAD as the reference, the subdistribution hazard ratio for ASCVD events was 4.0 (95% confidence interval [CI]: 3.3 to 4.9) for 1-vessel disease, 4.6 (3.5 to 6.0) for 2-vessel disease, and 5.6 (4.0 to 8.0) for 3-vessel disease. Consequently, the NNT to prevent 1 ASCVD event in 6 years by treating LDL-C to targets varied greatly from 233 (ESC) and 110 (ACC/AHA) for patients with no CAD to 8-9 for patients with 3-vessel disease (both ACC/AHA and ESC). The estimated percentage of ASCVD events that could be prevented by achieving guideline targets was 30% to 36% for patients with obstructive disease. However, <20% of patients achieved targets., Conclusions: An individualized approach based on CAD severity can identify symptomatic patients that are likely to derive most and least benefit from treating LDL-C to ACC/AHA and ESC treatment targets., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study was designed to compare head-to-head fractional flow reserve (FFR) derived from coronary computed tomography angiography (CTA) (FFR CT ) and cardiac magnetic resonance (CMR) stress perfusion imaging for prediction of standard-of-care-guided coronary revascularization in patients with stable chest pain and obstructive coronary artery disease by coronary CTA., Background: FFR CT is a novel modality for noninvasive functional testing. The clinical utility of FFR CT compared to CMR stress perfusion imaging in symptomatic patients with coronary artery disease is unknown., Methods: Prospective study of patients (n = 110) with stable angina pectoris and 1 or more coronary stenosis ≥50% by coronary CTA. All patients underwent invasive coronary angiography. Revascularization was FFR-guided in stenoses ranging from 30% to 90%. FFR CT  ≤0.80 in 1 or more coronary artery or a reversible perfusion defect (≥2 segments) by CMR categorized patients with ischemia. FFR CT and CMR were analyzed by core laboratories blinded for patient management., Results: A total of 38 patients (35%) underwent revascularization. Per-patient diagnostic performance for identifying standard-of-care-guided revascularization, (95% confidence interval) yielded a sensitivity of 97% (86% to 100%) for FFR CT versus 47% (31% to 64%) for CMR, p < 0.001; corresponding specificity was 42% (30% to 54%) versus 88% (78% to 94%), p < 0.001; negative predictive value of 97% (91% to 100%) versus 76% (67% to 85%), p < 0.05; positive predictive value of 47% (36% to 58%) versus 67% (49% to 84%), p < 0.05; and accuracy of 61% (51% to 70%) versus 74% (64% to 82%), p > 0.05, respectively., Conclusions: In patients with stable chest pain referred to invasive coronary angiography based on coronary CTA, FFR CT and CMR yielded similar overall diagnostic accuracy. Sensitivity for prediction of revascularization was highest for FFR CT, whereas specificity was highest for CMR., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Noninvasive fractional flow reserve derived from coronary CT angiography (FFR CT ) is increasingly used in patients with coronary artery disease as a gatekeeper to the catheterization laboratory. While there is emerging evidence of the clinical benefit of FFR CT in patients with moderate coronary disease as determined with coronary CT angiography, there has been less focus on interpretation, reporting, and integration of FFR CT results into routine clinical practice. Because FFR CT analysis provides a plethora of information regarding pressure and flow across the entire coronary tree, standardized criteria on interpretation and reporting of the FFR CT analysis result are of crucial importance both in context of the clinical adoption and in future research. This report represents expert opinion and recommendation on a standardized FFR CT interpretation and reporting approach. Published under a CC BY 4.0 license., Competing Interests: Disclosures of Conflicts of Interest: B.L.N. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: has received unrestricted institutional research grants from Siemens and HeartFlow; travel expenses covered at TCT 2017 by HeartFlow (no personal payment). Other relationships: disclosed no relevant relationships. T.A.F. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: has been an invited speaker sponsored by HeartFlow. Other relationships: disclosed no relevant relationships. R.D.S. disclosed no relevant relationships. M.G.R. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: author is consultant for HeartFlow. Other relationships: disclosed no relevant relationships. B.K. Activities related to the present article: has been an invited speaker at symposiums sponsored by Canon Medical, Medtronic, and St Jude, and has received research funding from Canon Medical. Activities not related to the present article: disclosed no relevant relationships. Other relationships: disclosed no relevant relationships. J.M.J. disclosed no relevant relationships. K.N. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: unrestricted institutional research support from HeartFlow, Siemens, GE, and Bayer; coverage of travel expenses to the present study results at the TCT in 2018 by HeartFlow; Steering committee ADVANCE registry for HeartFlow (unpaid). Other relationships: disclosed no relevant relationships. K.M.C. Activities related to the present article: institution receives grant from HeartFlow. Activities not related to the present article: Medical Advisory Board for HeartFlow (no personal compensation); institution receives grants from HeartFlow. Other relationships: disclosed no relevant relationships. N.P.S. disclosed no relevant relationships. H.M. disclosed no relevant relationships. J.L. Activities related to the present article: disclosed no relevant relationships. Activities not related to the present article: has received speaker honoraria from GE Healthcare, served as a consultant for Edwards Lifesciences, and served as a consultant and has stock options in Circle CVI and HeartFlow; has core laboratory contracts with Edwards Lifesciences, Medtronic, Abbott, Noevasc; research support from Edwards. Other relationships: disclosed no relevant relationships. G.R. disclosed no relevant relationships., (2019 by the Radiological Society of North America, Inc.)

Aim: To determine differences in coronary plaque composition and inflammatory biomarkers between men and women with newly diagnosed Type 2 diabetes without known cardiovascular disease., Methods: A total of 88 people with newly diagnosed (<1 year) Type 2 diabetes underwent contrast-enhanced coronary computed tomography angiography. Advanced coronary plaque analysis was performed using semi-automated software. Plasma concentrations of inflammatory biomarkers were determined., Results: There were no significant differences between men (n=60) and women (n=28) regarding age or cardiovascular risk factors (all P>0.05). The median (quartiles) serum levels of fibrinogen [10.9 (9.8-12.6) μmol/l vs 9.7 (8.8-10.9) μmol/l], fibrin d-dimer [0.3 (0.2-0.4) mg/l vs 0.27 (0.2-0.4) mg/l] and C-reactive protein [3.1 (1.1-5.2) mg/l vs (0.8-2.6) 1.6 mg/l] were significantly higher in women (all P<0.05). Overall, men more often had multi-vessel involvement [28 men (47%) vs 4 women (14%)], and higher total plaque burden [median (quartiles) 11.6 (2.3-36.0)% vs 2.0 (0.4-5.4)%; both P<0.05]. The median (quartiles) total plaque volume [269.9 (62.6-641.9) mm 3 vs 61.1 (7.6-239.9) mm 3 ] and absolute calcified plaque volume [33.5 (8.3-148.3) mm 3 vs 4.7 (0.9-17.3) mm 3 ] were higher in men (both P<0.05). Women had a lower relative proportion of the calcified plaque component [median (quartiles) 7.8 (4.7-15.4)% vs 23.7 (8.4-31.1)%] and a higher relative proportion (median [quartiles]) of the non-low-density non-calfied plaque component [77.6 (66.0-86.0)% vs 63.6 (54.0-72.9)%; both P<0.05]., Conclusions: In people with newly diagnosed Type 2 diabetes, women had lower absolute coronary plaque volumes but a more unfavourable plaque composition and enhanced systemic inflammation compared with men., (© 2018 Diabetes UK.)

Aims: Non-invasive assessment of stable chest pain patients is a critical determinant of resource utilization and clinical outcomes. Increasingly coronary computed tomography angiography (CCTA) with selective CCTA-derived fractional flow reserve (FFRCT) is being used. The ADVANCE Registry, is a large prospective examination of using a CCTA and FFRCT diagnostic pathway in real-world settings, with the aim of determining the impact of this pathway on decision-making, downstream invasive coronary angiography (ICA), revascularization, and major adverse cardiovascular events (MACE)., Methods and Results: A total of 5083 patients with symptoms concerning for coronary artery disease (CAD) and atherosclerosis on CCTA were enrolled at 38 international sites from 15 July 2015 to 20 October 2017. Demographics, symptom status, CCTA and FFRCT findings, treatment plans, and 90 days outcomes were recorded. The primary endpoint of reclassification between core lab CCTA alone and CCTA plus FFRCT-based management plans occurred in 66.9% [confidence interval (CI): 64.8-67.6] of patients. Non-obstructive coronary disease was significantly lower in ICA patients with FFRCT ≤0.80 (14.4%) compared to patients with FFRCT >0.80 (43.8%, odds ratio 0.19, CI: 0.15-0.25, P < 0.001). In total, 72.3% of subjects undergoing ICA with FFRCT ≤0.80 were revascularized. No death/myocardial infarction (MI) occurred within 90 days in patients with FFRCT >0.80 (n = 1529), whereas 19 (0.6%) MACE [hazard ratio (HR) 19.75, CI: 1.19-326, P = 0.0008] and 14 (0.3%) death/MI (HR 14.68, CI 0.88-246, P = 0.039) occurred in subjects with an FFRCT ≤0.80., Conclusions: In a large international multicentre population, FFRCT modified treatment recommendation in two-thirds of subjects as compared to CCTA alone, was associated with less negative ICA, predicted revascularization, and identified subjects at low risk of adverse events through 90 days.

Essentials Knowledge of genetic regulators of plasma factor VII activating protease (FSAP) levels is limited. We performed a genome-wide analysis of variants influencing FSAP activity in Scandinavian cohorts. We replicated an association for Marburg-1 and identified an association for a HABP2 stop variant. We identified a novel locus near ADCY2 as a potential additional regulator of FSAP activity., Summary: Background Factor VII-activating protease (FSAP) has roles in both coagulation and fibrinolysis. Recent data indicate its involvement in several other processes, such as vascular remodeling and inflammation. Plasma FSAP activity is highly variable among healthy individuals and, apart from the low-frequency missense variant Marburg-I (rs7080536) in the FSAP-encoding gene HABP2, determinants of this variation are unclear. Objectives To identify novel genetic variants within and outside of the HABP2 locus that influence circulating FSAP activity. Patients/Methods We performed an exploratory genome-wide association study (GWAS) on plasma FSAP activity amongst 3230 Swedish subjects. Directly genotyped rare variants were also analyzed with gene-based tests. Using GWAS, we confirmed the strong association between the Marburg-I variant and FSAP activity. HABP2 was also significant in the gene-based analysis, and remained significant after exclusion of Marburg-I carriers. This was attributable to a rare HABP2 stop variant (rs41292628). Carriers of this stop variant showed a similar reduction in FSAP activity as Marburg-I carriers, and this finding was replicated. A secondary genome-wide significant locus was identified at a 5p15 locus (rs35510613), and this finding requires future replication. This common variant is located upstream of ADCY2, which encodes a protein catalyzing the formation of cAMP. Results and Conclusions This study verified the Marburg-I variant to be a strong regulator of FSAP activity, and identified an HABP2 stop variant with a similar impact on FSAP activity. A novel locus near ADCY2 was identified as a potential additional regulator of FSAP activity., (© 2018 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.)

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

Background: To date, the clinical utility of coronary computed tomography angiography (CTA)-derived fractional flow reserve (FFRCT) has been limited to trials and single center experiences. We herein report the incidence of abnormal FFRCT (≤0.80) and the relationship of lesion-specific ischemia to subject demographics, symptoms, and degree of stenosis in the multicenter, prospective ADVANCE registry., Methods: One thousand patients with suspected angina having documented coronary artery disease on coronary CTA and clinically referred for FFR CT were prospectively enrolled in the registry. Patient demographics, symptom status, coronary CTA and FFR CT findings were recorded. Univariate and multivariate analyses were performed to investigate the predictors related to abnormal FFR CT ., Results: FFR CT data were analyzed in 952 patients (95.2%). Overall, 51.1% patients had a positive FFR CT value (≤0.80). Patients with ≥3 risk factors had a significantly higher rate of abnormal FFR CT than those with <3 risk factors (60.2% vs. 43.9%, p = 0.0001). On multivariate analysis, baseline diabetes (odds ratio [OR] 1.52, 95% confidence interval [CI] 1.04-2.21, p = 0.030) and hypertension (OR 1.56, 95%CI 1.14-2.14, p = 0.005) were both predictive of abnormal FFR CT . In addition, >70% stenosis was significantly associated with low FFR CT (OR 31.16, 95%CI 12.25-79.22, p < 0.0001) vs. <30% stenosis. Notably, stenosis 30-49% vs. <30% had an increased likelihood of ischemia (OR 3.74, 95%CI 1.52-9.17, p < 0.0001)., Conclusions: In this real-world registry, CT angiographic stenosis severity in addition to baseline cardiovascular risk factors conferred an increased likelihood of an abnormal FFR CT . Importantly, however, mild CT angiographic stenoses were noted to have an increased hazard for ischemia and the converse holding true for more severe stenoses as well., (Copyright © 2018 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

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.

Purpose of Review: To summarize the scientific basis of CT derived fractional flow reserve (FFR CT ) and present an updated review on the evidence from clinical trials and real-world observational data RECENT FINDINGS: In prospective multicenter studies of patients with stable coronary artery disease (CAD), FFR CT showed high diagnostic performance. More recently, FFR CT has advanced to the realm of clinical utility and real-world clinical practice with emerging data showing that FFR CT when compared to standard care is efficient in safely reducing downstream utilization of invasive coronary angiography (ICA), and costs, as well as improving the diagnostic yield of ICA. Moreover, FFR CT may broaden applicability of frontline coronary CTA testing to patients with high pre-test risk of CAD. Introducing FFR CT into clinical practice has the potential to significantly improve the management of patients with stable CAD. The optimal FFR CT testing interpretation strategy, as well as the relative cost-efficiency of FFR CT against standard noninvasive functional testing, need further investigation.

Objectives: This study sought to determine the incidence and progression of coronary artery calcification (CAC) in asymptomatic middle-aged subjects and to evaluate the value of a broad panel of biomarkers in the prediction of CAC growth., Background: CAC continues to be a major risk factor, but the value of biochemical markers in predicting CAC incidence and progression remains unresolved., Methods: At baseline, 1,227 men and women underwent traditional risk assessment and a computed tomography (CT) scan to determine the CAC score. Biomarkers of calcium-phosphate metabolism (calcium, phosphate, vitamin D 3 , parathyroid hormone, osteoprotegerin), lipid metabolism (triglyceride, high- and low-density lipoprotein, total cholesterol), inflammation (C-reactive protein, soluble urokinase-type plasminogen activator receptor), kidney function (creatinine, cystatin C, urate), and myocardial necrosis (cardiac troponin I) were analyzed. A second CT scan was scheduled after 5 years. General linear models were performed to examine the association between biomarkers and ΔCAC score, and additionally, sensitivity analyses were performed in terms of binary and ordinal logistic regressions., Results: A total of 1,006 participants underwent a CT scan after 5 years. Among the 562 participants with a baseline CAC score of 0, 189 (34%) had incident CAC, whereas 214 (48%) of the 444 participants with baseline CAC score >0 had significant progression (>15% annual increase in CAC score). In the multivariate models (n = 1,006), age, sex, hypertension, diabetes, dyslipidemia, and smoking were associated with ΔCAC, whereas the strongest predictor was baseline CAC score. Low-density lipoprotein and total cholesterol levels were independently associated with CAC incidence (n = 562; incidence rate ratio [IRR]: 1.47; 95% confidence interval [CI]: 1.05 to 2.05; and IRR: 1.34; 95% CI: 1.01 to 1.77, respectively), whereas phosphate level was associated with CAC progression (n = 444; IRR: 3.60; 95% CI: 1.42 to 9.11)., Conclusions: In this prospective study, a large part of participants had incident CAC or progression of prevalent CAC at 5 years of follow-up. Low-density lipoprotein and total cholesterol were associated with CAC incidence and phosphate with CAC progression, whereas 12 other biomarkers had little value., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For Permissions, please email: journals.permissions@oup.com.)

Background: Coronary CT angiography (CTA) is a reliable tool for the detection of coronary artery disease (CAD) that conveys significant prognostic information. It does not provide data on the hemodynamic significance of a given lesion, particularly in intermediate-grade stenosis. Fractional flow reserve by CT (FFR CT ) can accurately predict the hemodynamic significance of coronary lesions. The primary objective of this registry is to determine whether the integration of FFR CT as an adjunct to coronary CTA will lead to a significant change in the management of CAD in patients with stable angina., Methods: The ADVANCE Registry is a multi-center, prospective registry designed to evaluate utility, clinical outcomes and resource utilization following FFR CT -guided treatment in clinically stable, symptomatic patients diagnosed with CAD by coronary CTA. Approximately 5000 patients will be enrolled from up to 50 sites in Europe, USA, Canada and Asia. Requirement for enrollment is the presence of atherosclerosis on coronary CTA. For each enrolled patient, a clinical management review committee will use data from coronary CTA and FFR CT to determine the management plan using the following criteria: (a) optimal medical therapy, (b) percutaneous coronary intervention, (c) coronary artery bypass graft surgery, or (d) more information required. The primary endpoint of the registry is the reclassification rate between the management plan based on coronary CTA alone versus CTA plus FFR CT . The secondary endpoints of the registry include the evaluation of the rate of invasive coronary angiography (ICA), revascularization, major adverse coronary events, resource utilization, cumulative radiation dose exposure and the rate of ICA without obstructive CAD at 3-year follow-up., Conclusions: The ADVANCE registry is designed to assess the real-world impact of FFR CT on the clinical management of stable CAD when used along with coronary CTA., (Copyright © 2016 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Background: High-sensitive troponin I (hs-TnI) is an individual predictor of future cardiovascular disease (CVD). However, the relationship between hs-TnI and coronary artery calcification (CAC) as determined by computed tomography (CT) has not previously been investigated in a general population., Methods: 1173 randomized, middle-aged subjects without known CVD underwent a non-contrast cardiac-CT scan for CAC determination. Hs-TnI was detected using ARCHITECT STAT High Sensitive Troponin-I immunoassay. Total 10-year cardiovascular mortality risk was estimated using HeartScore. The relationship between hs-TnI and CAC was assessed using logistic regression analyses and receiver operating characteristic curves (ROC)., Results: Concentrations of hs-TnI above the limit of detection were measured in 89.3% of all subjects. Presence of CAC (Agatston score >0) was detected in 29% in the lowest hs-TnI quartile compared with 55% in the highest, with a stepwise increase over the quartiles. In fully adjusted regression models with dichotomous CAC outcomes, hs-TnI was able to predict presence of CAC (OR: 1.25, 95% CI: 1.03-1.51, p = 0.025) and an Agatston score >100 (OR: 1.36, 95% CI: 1.08-1.71, p = 0.009). Subjects in the fourth hs-TnI quartile had an increased risk for presence of CAC (OR: 1.56, 95% CI: 1.06-2.26, p = 0.024) and for an Agatston score >100 (OR: 1.82, 95% CI: 1.04-3.18, p = 0.035), when compared with the first quartile. Addition of hs-TnI to HeartScore improved the ROCAUC from 0.671 to 0.695 (p < 0.0001)., Conclusion: Hs-TnI was associated with CAC in a Danish middle-aged population without previously known CVD. This is a step towards understanding hs-TnI as a risk marker for CVD., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Fractional flow reserve (FFR) measured during invasive coronary angiography is an independent prognosticator in patients with coronary artery disease and the gold standard for decision making in coronary revascularization. The integration of computational fluid dynamics and quantitative anatomic and physiologic modeling now enables simulation of patient-specific hemodynamic parameters including blood velocity, pressure, pressure gradients, and FFR from standard acquired coronary computed tomography (CT) datasets. In this review article, we describe the potential impact on clinical practice and the science behind noninvasive coronary computed tomography (CT) angiography derived fractional flow reserve (FFR CT ) as well as future applications of this technology in treatment planning and quantifying forces on atherosclerotic plaques.

Background: Coronary artery calcification (CAC) can be detected by cardiac computed tomography (CT), is associated to cardiovascular risk, and common in asymptomatic individuals and patients referred for cardiac CT., Design: CAC was evaluated in asymptomatic individuals and symptomatic patients referred for cardiac CT, to assess whether differences in CAC may be explained by symptoms or traditional cardiovascular risk factors., Methods: The presence and extent of CAC, gender, family history of coronary artery disease, hypertension, hyperlipidaemia, diabetes and tobacco were compared in 1220 asymptomatic individuals aged 49-61 years and 2257 age-matched symptomatic patients referred for cardiac CT with suspected coronary artery disease., Results: Symptomatic individuals had a higher frequency of a family history of coronary artery disease (46% vs. 23%, p < 0.001), hypertension (38% vs. 21%, p < 0.001), hyperlipidaemia (42% vs. 12%, p < 0.001), a trend for more diabetes (6% vs. 5%, p = 0.05), but no significant difference was observed for the presence of CAC (Agatston > 0; 45% vs. 45%, p = 0.94) or severe calcifications (Agatston > 400; 6% vs. 5%, p = 0.36). In multivariate analyses age (odds ratio (OR) 1.09-1.18), male gender (OR 3.5-6.43), hypertension (OR 1.42-1.79), hyperlipidaemia (OR 1.86-2.09) and tobacco use (OR 1.83-2.01) were predictors for the presence and extent of CAC, whereas symptoms were not predictive for the presence of (Agatston > 0, OR 0.70 (0.59-0.83)), mild (Agatston ≥ 10; OR 0.85 (0.71-1.02)), moderate (Agatston ≥ 100; OR 0.99 (0.79-1.24)) or severe calcifications (Agatston ≥ 400; OR 0.93 (0.65-1.33))., Conclusion: No difference in the presence or severity of coronary calcifications was observed between asymptomatic and symptomatic middle-aged individuals. After adjusting for cardiovascular risk factors, symptoms were not predictive for the presence or extent of CAC., (© The European Society of Cardiology 2015.)

Objectives: Direct health provider to patient presentation of coronary computed tomography angiography findings may increase adherence to preventive therapy and risk modification. The purpose of this study was to assess the influence of visualization of coronary artery calcification and lifestyle recommendations on cholesterol concentrations and other risk variables in symptomatic patients with nonobstructive coronary artery disease and hyperlipidemia., Methods: We performed a prospective 2-center randomized controlled trial. Patients were randomized 1:1 to intervention or standard follow-up in general practice. The primary end point was change in plasma total cholesterol concentration at 6 months follow-up., Results: We included 189 patients (mean [± standard deviation] age 61 [12] years, 57% were male). Median (range) Agatston score was 166 (70-2054). The reduction in plasma total cholesterol concentrations tended to be higher in the intervention group than in the control group, 51.04 mg/dL versus 45.63 mg/dL (P = .181). In a subgroup including patients continuing statin therapy during follow-up (n = 147), the reduction in plasma total cholesterol concentrations was more pronounced in the intervention group than in the control group, 66.13 mg/dL versus 55.68 mg/dL (P = .027). In the intervention group, there was a higher degree of statin adherence and a higher proportion of patients who stopped smoking and commenced healthier dietary behavior than in the control group., Conclusions: Visualization of coronary artery calcification and brief recommendations about risk modification after coronary computed tomography angiography in symptomatic patients with nonobstructive coronary artery disease and hyperlipidemia may have a favorable influence on plasma total cholesterol concentration, adherence to statin therapy, and risk behavior. Further investigations are needed., (Copyright © 2015 Elsevier Inc. All rights reserved.)

We conducted a 1:2 matched case-control study in order to evaluate whether the prevalence of coronary artery calcium (CAC) and electrocardiographic left ventricular hypertrophy (LVH) or strain was higher in patients with uncontrolled hypertension than in subjects from the general population, and evaluate the association between CAC and LVH in patients with uncontrolled hypertension. Cases were patients with uncontrolled hypertension, whereas the controls were random individuals from the general population without cardiovascular disease. CAC score was assessed using a non-contrast computed tomographic scan. LVH was evaluated using the Sokolow-Lyon voltage combination and Cornell voltage-duration product, respectively. Associations between CAC, LVH and traditional cardiovascular risk factors were tested by means of ordinal, conditional and classic binary logistic regression models. We found that uncontrolled hypertension was independently associated with both an ordinal CAC score category (odds ratio (OR) 3.9 (95% CI, 1.6-9.1), P = 0.002), the presence of CAC score>99 (OR 4.5 (95% CI, 1.4-14.7), P = 0.01) and electrocardiographic LVH (OR 10.1 (95% CI, 3.4-30.2), P < 0.001) on both univariate and multivariable analyses. There was, however, no correlation between CAC and LVH. The lack of an association between CAC and LVH suggests that they are markers of different complications of hypertension and may have independent predictive values. Patients with both CAC and LVH may be at higher risk than those in whom only one of these markers is present.

Objectives: The European HeartScore has traditionally differentiated between low and high-risk countries. Until 2012 Germany and Denmark were considered to be high-risk countries but have now been defined as low-risk countries. In this survey we aim to address the consequences of this downgrading., Methods: A screening of 3932 randomly selected (mean age 56 years, 46% male) individuals from Germany and Denmark free of cardiovascular disease was performed. Traditional risk factors were determined, and the HeartScore was measured using both the low-risk and the high-risk country models. A non-contrast Cardiac-CT scan was performed to detect coronary artery calcification (CAC)., Results: Agreement of HeartScore risk groups with CAC groups was poor, but higher when applying the algorithm for the low-risk compared to the high-risk country model (agreement rate: 77% versus 63%, and weighted Kappa: 0.22 versus 0.15). However, the number of subjects with severe coronary calcification (CAC score ≥400) increased in the low and intermediate HeartScore risk group from 78 to 147 participants (from 2.7 % to 4.2 %, p = 0.001), when estimating the risk based on the algorithm for low-risk countries., Conclusion: As a consequence of the reclassification of Germany and Denmark as low-risk countries more people with severe atherosclerosis will be classified as having a low or intermediate risk of fatal cardiovascular disease., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: As a subregistry to the Western Denmark Heart Registry (WDHR), the Western Denmark Cardiac Computed Tomography Registry (WDHR-CCTR) is a clinical database established in 2008 to monitor and improve the quality of cardiac computed tomography (CT) in Western Denmark., Objective: We examined the content, data quality, and research potential of the WDHR-CCTR., Methods: We retrieved 2008-2012 data to examine the 1) content; 2) completeness of procedure registration using the Danish National Patient Registry as reference; 3) completeness of variable registration comparing observed vs expected numbers; and 4) positive predictive values as well as negative predictive values of 19 main patient and procedure variables., Results: By December 31, 2012, almost 22,000 cardiac CTs with up to 40 variables for each procedure have been registered. Of these, 87% were coronary CT angiography performed in patients with symptoms indicative of coronary artery disease. Compared with the Danish National Patient Registry, the overall procedure completeness was 72%. However, an additional medical record review of 282 patients registered in the Danish National Patient Registry, but not in the WDHR-CCTR, showed that coronary CT angiographies accounted for only 23% of all nonregistered cardiac CTs, indicating >90% completeness of coronary CT angiographies in the WDHR-CCTR. The completeness of individual variables varied substantially (range: 0%-100%), but was >85% for more than 70% of all variables. Using medical record review of 250 randomly selected patients as reference standard, the positive predictive value for the 19 variables ranged from 89% to 100% (overall 97%), whereas the negative predictive value ranged from 97% to 100% (overall 99%). Stratification by center status showed consistently high positive and negative predictive values for both university (96%/99%) and nonuniversity centers (97%/99%)., Conclusion: WDHR-CCTR provides ongoing prospective registration of all cardiac CTs performed in Western Denmark since 2008. Overall, the registry data have a high degree of completeness and validity, making it a valuable tool for clinical epidemiological research.

Objective: The main objective of this study was to investigate the association between two markers of low-grade inflammation; soluble urokinase plasminogen activator receptor (suPAR) and high-sensitive C-reactive protein (hs-CRP); and coronary artery calcification (CAC) score detected by cardiac computed tomography (CT) scan., Design: A cross sectional study of 1126 randomly sampled middle-aged men and women., Methods: CAC score was measured by a non-contrast cardiac CT scan and total 10-year cardiovascular mortality risk was estimated using the Systematic Coronary Risk Evaluation (SCORE). Plasma samples were analysed for suPAR and hs-CRP. The association of suPAR and hs-CRP to CAC was evaluated by logistic regression analyses adjusting for categorised SCORE. The additive effect of suPAR to SCORE was evaluated by comparing area under curve (AUC) and net reclassification improvement (NRI)., Results: The odds of being in a higher CAC category, i.e. having more severe CAC, increased 16% (odds ratio (OR) 1.16, p = 0.02) when plasma suPAR concentration increased 1 ng/ml, and this was more pronounced in women (OR 1.30, p = 0.01) than in men (OR 1.15, p = 0.05). In comparison, hs-CRP was not associated with CAC category (OR 1.00, p = 0.90). When adding suPAR to categorised SCORE, AUC increased from 0.66 to 0.70 (p = 0.04) in women and from 0.65 to 0.68 (p = 0.03) in men. NRI was significant in men (NRI 19.3%, 95% CI 6.1-32.6, p = 0.004) as well as in women (NRI 20.8%, 95%CI 1.0-40.7, p = 0.04), without significant gender difference., Conclusions: suPAR, but not hs-CRP, appeared to be associated with CAC score independently of SCORE. The association was strongest in women., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Recently, copeptin was found associated with cardiovascular disease (CVD) and all-cause mortality in type 2 diabetes mellitus (T2DM) patients treated in primary care. This study aimed to evaluate whether plasma copeptin correlated to CVD in asymptomatic T2DM patients intensively investigated for sub-clinical CVD. A total of 302 T2DM patients referred to the Diabetes Clinic at Odense University Hospital, Denmark, entered the study. None of the patients had known or suspected CVD. As a control group, 30 healthy adults were recruited from the DanRisk study - a random sample of middle-aged Danes. A variety of clinical investigations were performed, including blood pressure measurements, carotid intima media thickness evaluation and myocardial perfusion scintigraphy. Blood sample analyses included copeptin measurements. Median plasma copeptin concentrations were similar in the T2DM group and the control group. However, men had significantly higher copeptin concentrations than women in the T2DM group (p < 0.001), and also, T2DM men had significantly higher copeptin concentrations than men without T2DM (p = 0.038). Copeptin correlated significantly with a number of variables, but the strongest correlation was with creatinine (R = 0.432, p < 0.001), and in multiple regression analysis, only this correlation remained significant. When association with clinical scores were investigated, plasma copeptin remained significantly associated with peripheral arterial disease (PAD) (p = 0.01). We found correlations between creatinine, copeptin levels and PAD in T2DM patients, and if confirmed, plasma copeptin combined with plasma creatinine could be a candidate for PAD screening in T2DM patients., (© The Author(s) 2014.)

Purpose: The biomarker Osteoprotegerin (OPG) is associated with coronary artery disease (CAD). The main purpose of this study was to evaluate the diagnostic value of OPG in healthy subjects and in patients with suspected angina pectoris (AP)., Methods: A total of 1805 persons were enrolled: 1152 healthy subjects and 493 patients with suspected AP. For comparison 160 patients with acute myocardial infarction (MI) were included. To uncover subclinical coronary atherosclerosis, a non-contrast cardiac-CT scan was performed in healthy subjects; while in patients with suspected AP a contrast coronary angiography was used to detect significant stenosis. OPG concentrations were analyzed and compared between groups. ROC-analyses were performed to estimate OPG cut-off values., Results: OPG concentrations increased according to disease severity with the highest levels found in patients with acute MI. No significant difference (p = 0.97) in OPG concentrations was observed between subgroups of healthy subjects according to severity of coronary calcifications. A significant difference (p < 0.0001) in OPG concentrations was found between subgroups of patients with suspected stable AP according to severity of CAD. ROC-analysis showed an AUC of 0.62 (95% CI: 0.57-0.67). The optimal cut-off value of OPG (<2.29 ng/mL) had a sensitivity of 56.2% (95% CI: 49.2-63.0%) and a specificity of 62.9% (95% CI: 57.3-68.2%)., Conclusion: OPG cannot be used to differentiate between healthy subjects with low versus high levels of coronary calcifications. In patients with suspected AP a single OPG measurement is of limited use in the diagnosis of CAD., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Aims: Understanding the determinants of social and coping inequalities in subclinical cardiovascular disease is an important prerequisite in developing and implementing preventive strategies. The aim of this study was to investigate the association between social factors and coping status, respectively, and subclinical coronary artery disease (CAD) in middle-aged Danes., Methods: This is a DanRisk screening substudy, thus including healthy Danish males and females aged 50 or 60 years. Social measures included grade of education, employment and co-habiting status. The coping status was estimated by the general self-efficacy (GES) scale. Coronary artery calcification (CAC) was assessed by computed tomography using the Agatston score (AS). Conventional clinical risk factors included sex, family history of CAD, BMI > 25, smoking, hypercholesterolaemia and hypertension., Results: In 568 individuals the prevalence of subjects with CAC was 267 (45%). Independent predictors of CAC in males were age (OR = 1.10, 95% CI = 1.04-1.16, p < 0.001), smoking (OR = 1.75, 95% CI = 1.03-2.99, p = 0.038), and low co-habiting status (OR = 3.66, 95% CI = 1.19-11.25, p = 0.023). Independent predictors in females were age (OR = 1.67, 95% CI = 1.02-1.12, p = 0.006), and smoking (OR = 1.71, 95% CI = 1.06-2.78, p = 0.029). Higher AS was associated to lower employment level in females (p = 0.001) but not in males (p = 0.833)., Conclusions: Social factors are associated to the prevalence and severity of CAC in asymptomatic middle-aged individuals with gender differences. The relative value of gender specific social versus conventional clinical risk factors in the risk assessment of subclinical CAC in middle-aged individuals needs further investigation in future prospective studies.

Background: Depression is associated with coronary artery disease, and atherosclerosis seems to play a central role in this relation. In several studies, multislice computed tomography (CT) has been applied for detection and quantification of coronary artery calcification (CAC) in relation to depression. To our knowledge, only one previous study has investigated the relation between CAC and depression in an unselected population., Methods: A total of 617 persons were randomly selected from the background population. The participants underwent CT of the heart and were screened for depression by use of the Major Depression Inventory questionnaire. Quantification of CAC was performed using the Agatston method. The Mann-Whitney U test, Spearman's correlational analysis, and logistic regression were used to assess the association between depression and CAC., Results: The median Agatston score was not significantly different in subjects with depression than in those without depression (p = 0.783), and depression scores did not correlate significantly with Agatston scores (r = 0.023; 95% CI: -0.056-0.102; p = 0.573). This was also the case when correlational analyses were stratified by sex or age. Furthermore, after the exclusion of an outlier, no significant association between CAC and depression was found in either the unadjusted or adjusted logistic regression model, OR = 1.00 (95% CI: 0.88-1.14; p = 0.994) and OR = 1.04 (95% CI: 0.92-1.18; p = 0.529), respectively., Conclusions: Depression was not associated with CAC in an unselected middle-aged population, although a trend-level association was found in men (p = 0.086)., (Copyright © 2013 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Von Willebrand factor (VWF) is pivotal in arterial thrombosis, and osteoprotegerin (OPG) is besides being a bone protein also related to cardiovascular diseases. OPG can bind VWF, but the significance of this interaction is not known., Objectives: The aim was to develop an assay for measurement of von Willebrand factor-osteoprotegerin complex (VWF:OPG) in human plasma. Furthermore, the significance of VWF:OPG complex as a marker of cardiovascular disease (CVD) was evaluated., Patients/methods: A sandwich ELISA for quantification of VWF:OPG was developed using a polyclonal rabbit anti-human VWF capturing antibody and a monoclonal anti-human OPG detecting antibody. Samples were quantified relative to a standard curve obtained from dilutions of a plasma pool from healthy individuals. The assay was evaluated in two groups of patients with CVD and two groups of asymptomatic individuals with and without documented coronary calcification (total n=118)., Results and Conclusions: The assay detected VWF:OPG complexes in human plasma, while no significant signal was observed when testing solutions containing VWF or recombinant OPG alone. Importantly, the ELISA assay was able to detect in vitro formed complexes between human VWF and recombinant OPG in a dose-dependent manner. There was a large inter-individual variation in plasma VWF:OPG levels, but we found no significant differences in the level of VWF:OPG complexes between the four groups. Thus, we conclude that increasing OPG plasma levels in atherosclerotic CVD are not derived from increased levels of complexed form of VWF and OPG, but are more likely due to increased amounts of OPG secreted into the circulation., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Purpose: To improve risk stratification for development of ischaemic heart disease, several markers have been proposed. Both the presence of coronary artery calcification (CAC) and ECG pattern of left ventricular hypertrophy/strain have been shown to provide independent prognostic information. In this study, we investigated the association between established risk factors, ECG measurements and the presence of coronary artery calcification., Method: A random sample of healthy men and women aged 50 or 60 years were invited to the screening study. Established risk factors were measured. A noncontrast computed tomographic (CT) scan was performed to assess the CAC score. ECG analysis included left ventricular hypertrophy (LVH) using the Sokolow-Lyon criteria and the Cornell voltage × QRS duration product, and strain pattern based on ST segment depression and T-wave abnormalities. The association between the presence of CAC, clinical variables and ECG findings was evaluated by means of multivariate logistic regression., Results: Of 1825 invited individuals, 1226 accepted the screening. The prevalence of hypertension was 50%. Hypertensive patients frequently had LVH and/or strain when compared with nonhypertensive individuals (21 vs. 14%, P < 0.0001) as well as CAC (52 vs. 38%, P < 0.0001). In multiple logistic regressions analyses, there was no association between the ECG abnormalities and the presence of CAC., Conclusion: There appears to be no relationship between CAC and ECG-suspected LVH and/or strain. We propose that these markers identify different individuals at risk and together may have additive prognostic value.

Screening of the general population for subclinical atherosclerosis is controversial. We assessed the prevalence of subclinical atherosclerosis in healthy middle-aged individuals by 4 non-invasive modalities. In 277 randomly selected males (n = 121) and females (n = 156), aged 50 or 60 years, without known cardiovascular disease or diabetes, intima-media thickness/presence of carotid plaques by ultrasound; coronary artery calcification (CAC) by non-contrast enhanced cardiac CT; occurrence of peripheral artery disease (PAD) by ankle brachial index (ABI), and vascular leakage by urine albumin creatinine ratio (ACR), were evaluated. Traditional risk factors were obtained and HeartScore was calculated. A total of 56 % had morphological signs of atherosclerosis in one of the vascular territories; 41 % had CAC and 31 % a carotid plaque. Among individuals with atherosclerosis, 28 % had lesions in both vascular territories. Subclinical atherosclerosis was significantly more frequent in older males. Signs of PAD and microalbuminuria were very uncommon and detected in only 1 % of the entire population. No association was found between morphological signs of subclinical atherosclerosis and ABI or ACR. More than half of randomly selected apparently healthy middle aged individuals had subclinical atherosclerosis located in the coronary or carotid arteries.

Objectives: The aim was to examine and compare the impact of HeartScore and coronary artery calcification (CAC) score on subsequent changes in the use of medication., Methods: A total of 1156 healthy men and women, aged 50 or 60, had a baseline medical examination and a coronary artery CT-scan as a part of a screening programme. Using the European HeartScore, the total 10-year cardiovascular mortality risk was estimated (≥5% risk was considered as high). Risk factors and CAC scores were reported to both the patients and their general practitioner. Six months after the screening, follow-up questionnaires addressing current medication were mailed to the participants., Results: A completed questionnaire was returned by 1075 (93%) subjects. At follow up, the overall use of prophylactic medication was significantly increased. Of those with CAC (n = 462) or high HeartScore (n = 233), 21 and 19%, respectively, received lipid-lowering treatment, while 25 and 32%, respectively, received antihypertensive treatment. In multivariate logistic regression analyses, the presence of CAC was associated with an increased use of lipid-lowering treatment (OR 2.2; 95% CI 1.2-4.0), while the presence of a high HeartScore was associated with an increased use of lipid-lowering (OR 2.9; 95% CI 1.6-5.5) and antihypertensive medication (OR 3.4; 95% CI 1.9-6.0)., Conclusion: Knowledge of present cardiovascular risk factors like high HeartScore and/or CAC leads to beneficial changes in medication. However, at follow up only a minority of high-risk subjects did received prophylactic treatment. CAC score was not superior to HeartScore regarding these motivational outcomes.

Background: Coronary artery calcification (CAC) is an independent and incremental risk marker. This marker has previously not been compared to the HeartScore risk model., Design: A random sample of 1825 citizens (men and women, 50 or 60 years of age) was invited for screening., Methods: Using the HeartScore model, the 10-year risk of fatal cardiovascular events based on gender, age, smoking, systolic blood pressure, and total cholesterol was estimated. A low risk was defined as <5%. The CAC score was calculated from a non-contrast enhanced cardiac-CT scan and given in Agatston U., Results: A total of 1257 (69%) of the invited subjects were interested in the screening. Due to previous cardiovascular disease or diabetes mellitus, 101 were excluded. Of the remaining 1156, 47% were men and 53% women; one half were 50 years old and the other half 60 years old. A low HeartScore was found in 901 of which 334 (37%) had CAC. A high HeartScore was recorded in 251 of which 80 (32%) did not have any CAC. High HeartScores and CAC were significantly more common in males than females., Conclusions: CAC is common in healthy middle-aged Danes with a low HeartScore, and, on the contrary, high-risk subjects very frequently do not have CAC. The therapeutic and prognostic implications of these observations remain to be clarified.

Objective: To evaluate the association between the risk factor for living in the city centre as a surrogate for air pollution and the presence of coronary artery calcification (CAC) in a population of asymptomatic Danish subjects., Design and Subjects: A random sample of 1825 men and women of either 50 or 60 years of age were invited to take part in a screening project designed to assess risk factors for cardiovascular disease (CVD). Noncontrast cardiac computed tomography was performed on all subjects, and their Agatston scores were calculated to evaluate the presence of subclinical coronary atherosclerosis. The relationship between CAC and several demographic and clinical parameters was evaluated using multivariate logistic regression., Results: A total of 1225 individuals participated in the study, of whom 250 (20%) were living in the centres of major Danish cities. Gender and age showed the greatest association with the presence of CAC: the odds ratio (OR) for men compared with women was 3.2 [95% confidence interval (CI) 2.5-4.2; P < 0.0001], and the OR for subjects aged 60 versus those aged 50 years was 2.2 (95% CI 1.7-2.8; P < 0.0001). Other variables independently associated with the presence of CAC were diabetes and smoking with ORs of 2.0 (95% CI 1.1-3.5; P = 0.03) and 1.9 (95% CI 1.4-2.5, P < 0.0001), respectively. The adjusted OR for subjects living in city centres compared to those living outside was 1.8 (95% CI 1.3-2.4; P = 0.0003)., Conclusion: Both conventional risk factors for CVD and living in a city centre are independently associated with the presence of CAC in asymptomatic middle-aged subjects., (© 2011 The Association for the Publication of the Journal of Internal Medicine.)

Background: Interruption in chest compressions during cardiopulmonary resuscitation can be characterized as no flow ratio (NFR) and the importance of minimizing these pauses in chest compression has been highlighted recently. Further, documentation of resuscitation performance has been reported to be insufficient and there is a lack of identification of important issues where future efforts might be beneficial. By implementing in situ simulation we created a model to evaluate resuscitation performance. The aims of the study were to evaluate the feasibility of the applied method, and to examine differences in the resuscitation performance between the first responders and the cardiac arrest team., Methods: A prospective observational study of 16 unannounced simulated cardiopulmonary arrest scenarios was conducted. The participants of the study involved all health care personel on duty who responded to a cardiac arrest. We measured NFR and time to detection of initial rhythm on defibrillator and performed a comparison between the first responders and the cardiac arrest team., Results: Data from 13 out of 16 simulations was used to evaluate the ability of generating resuscitation performance data in simulated cardiac arrest. The defibrillator arrived after median 214 seconds (180-254) and detected initial rhythm after median 311 seconds (283-349). A significant difference in no flow ratio (NFR) was observed between the first responders, median NFR 38% (32-46), and the resuscitation teams, median NFR 25% (19-29), p < 0.001. The difference was significant even after adjusting for pulse and rhythm check and shock delivery., Conclusion: The main finding of this study was a significant difference between the first responders and the cardiac arrest team with the latter performing more adequate cardiopulmonary resuscitation with regards to NFR. Future research should focus on the educational potential for in-situ simulation in terms of improving skills of hospital staff and patient outcome.