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Aims: To date, no studies have investigated the association between lipid species and coronary plaque changes over time, quantitatively assessed by serial imaging. We aimed to prospectively determine the association between lipid species quantified by a plasma lipidomic analysis and coronary plaque changes according to composition assessed by a quantitative serial analysis of coronary computed tomography angiography (CTA)., Methods and Results: Patients with suspected coronary artery disease (CAD) undergoing baseline coronary CTA were prospectively enrolled by seven EU centres in the SMARTool study and submitted to clinical, molecular, and coronary CTA re-evaluation at follow-up (an inter-scan period of 6.39 ± 1.17 years). Out of 202 patients who were analysed in the SMARTool main clinical study, a lipidomic analysis was performed in 154 patients before the baseline coronary CTA, and this group was included in the present study. A quantitative CTA analysis was performed by using a separate core laboratory blinded from clinical data. In the univariable analysis, it was found that no lipid species were significantly associated with annual total and calcified plaque changes. After adjusting for clinical variables at baseline and statin use, it was found that three lipid species were significantly associated with non-calcified plaque progression. In detail, cholesteryl ester(20:3), sphingomyelin (SM)(40:3), and SM(41:1) were found to be positively related to non-calcified plaque progression (Bonferroni-adjusted P-values = 0.005, 0.016, and 0.004, respectively)., Conclusion: The current study showed an independent relationship between specific lipid species determined by a plasma lipidomic analysis and non-calcified coronary plaque progression assessed by a serial, quantitative coronary CTA analysis., Competing Interests: Conflict of interest: A.S. received fees for consultancy or lectures from Abbot, Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, and Pfizer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: We assessed whether combinations of cardiometabolic risk factors independently predict coronary plaque progression (PP) and major adverse cardiovascular events in patients with stable coronary artery disease., Methods: Patients with known or suspected stable coronary artery disease (60.9±9.3 years, 55.4% male) undergoing serial coronary computed tomography angiographies (≥2 years apart), with clinical characterization and follow-up (N=1200), were analyzed from the PARADIGM study (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging). Plaque volumes measured in coronary segments (≥2 mm in diameter) were summed to provide whole heart plaque volume (mm 3 ) and percent atheroma volume (plaque volume/vessel volume×100; %) per patient at baseline and follow-up. Rapid PP was defined as a percent atheroma volume increase of ≥1.0%/y. Major adverse cardiovascular events included nonfatal myocardial infarction, death, and unplanned coronary revascularization., Results: In an interscan period of 3.2 years (interquartile range, 1.9), rapid PP occurred in 341 patients (28%). At multivariable analysis, the combination of cardiometabolic risk factors defined as metabolic syndrome predicted rapid PP (odds ratio, 1.51 [95% CI, 1.12-2.03]; P =0.007) together with older age, smoking habits, and baseline percent atheroma volume. Among single cardiometabolic variables, high fasting plasma glucose (diabetes or fasting plasma glucose >100 mg/dL) and low HDL-C (high-density lipoprotein cholesterol; <40 mg/dL in males and <50 mg/dL in females) were independently associated with rapid PP, in particular when combined (odds ratio, 2.37 [95% CI, 1.56-3.61]; P <0.001). In a follow-up of 8.23 years (interquartile range, 5.92-9.53), major adverse cardiovascular events occurred in 201 patients (17%). At multivariable Cox analysis, the combination of high fasting plasma glucose with high systemic blood pressure (treated hypertension or systemic blood pressure >130/85 mm Hg) was an independent predictor of events (hazard ratio, 1.79 [95% CI, 1.10-2.90]; P =0.018) together with family history, baseline percent atheroma volume, and rapid PP., Conclusions: In patients with stable coronary artery disease, the combination of hyperglycemia with low HDL-C is associated with rapid PP independently of other risk factors, baseline plaque burden, and treatment. The combination of hyperglycemia with high systemic blood pressure independently predicts the worse outcome beyond PP., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02803411., Competing Interests: Dr Chang receives funding from the Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Korea funded by the Ministry of Science and ICT (grant No. 2012027176). Dr Min receives funding from GE Healthcare and serves on the scientific advisory board of Arineta and GE Healthcare. Dr Min also has an equity interest in and is an employee of Cleerly Inc. The other authors report no conflicts.

Background: The endothelial nitric oxide synthase (eNOS) gene deficiency is known to cause impaired coronary vasodilating capability in animal models. In the general clinical population, the eNOS gene polymorphisms, able to affect eNOS activity, were associated with cardiometabolic risk features and prevalence of coronary artery disease (CAD)., Aim: To investigate the association of eNOS Glu298Asp gene polymorphism, cardiometabolic profile, obstructive CAD and inducible myocardial ischemia in patients with suspected stable CAD., Methods: A total of 506 patients (314 males; mean age 62 ± 9 years) referred for suspected CAD was enrolled. Among these, 325 patients underwent stress ECG or cardiac imaging to assess the presence of inducible myocardial ischemia and 436 patients underwent non-invasive computerized tomography or invasive coronary angiography to assess the presence of obstructive CAD. Clinical characteristics and blood samples were collected for each patient., Results: In the whole population, 49.6% of patients were homozygous for the Glu298 genotype (Glu/Glu), 40.9% heterozygotes (Glu/Asp) and 9.5% homozygous for the 298Asp genotype (Asp/Asp). Obstructive CAD was documented in 178/436 (40.8%) patients undergoing coronary angiography while myocardial ischemia in 160/325 (49.2%) patients undergoing stress testing. Patients with eNOS Asp genotype (Glu/Asp + Asp/Asp) had no significant differences in clinical risk factors and in circulating markers. Independent predictors of obstructive CAD were age, gender, obesity, and low HDL-C. Independent predictors of myocardial ischemia were gender, obesity, low HDL-C and Asp genotype. In the subpopulation in which both stress tests and coronary angiography were performed, the Asp genotype remained associated with increased myocardial ischemia risk after adjustment for obstructive CAD., Conclusion: In this population, low-HDL cholesterol was the only cardiometabolic risk determinant of obstructive CAD. The eNOS Glu298Asp gene polymorphism was significantly associated with inducible myocardial ischemia independently of other risk factors and presence of obstructive CAD., (© 2024. The Author(s).)

Background and Aims: MMP-9 is a predictor of atherosclerotic plaque instability and adverse cardiovascular events, but longitudinal data on the association between MMP9 and coronary disease progression are lacking. This study is aimed at investigating whether MMP9 is associated with atherosclerotic plaque progression and the related molecular basis in stable patients with chronic coronary syndrome (CCS)., Methods: MMP9 serum levels were measured in 157 CCS patients (58 ± 8 years of age; 66% male) undergoing coronary computed tomography angiography at baseline and after a follow up period of 6.5 ± 1.1 years to assess progression of Total, Fibrous, Fibro-fatty, Necrotic Core, and Dense Calcium plaque volumes (PV). Gene expression analysis was evaluated in whole blood using a transcriptomic approach by RNA-seq., Results: At multivariate analysis, serum MMP9 was associated with annual change of Total and Necrotic Core PV (Coefficient 3.205, SE 1.321, P = 0.017; 1.449, SE 0.690, P = 0.038, respectively), while MMP9 gene expression with Necrotic Core PV (Coefficient 70.559, SE 32.629, P = 0.034), independently from traditional cardiovascular risk factors, medications, and presence of obstructive CAD. After transcriptomic analysis, MMP9 expression was linked to expression of genes involved in the innate immunity., Conclusions: Among CCS patients, MMP9 is an independent predictive marker of progression of adverse coronary plaques, possibly reflecting the activity of inflammatory pathways conditioning adverse plaque phenotypes. Thus, blood MMP9 might be used for the identification of patients with residual risk even with optimal management of classical cardiovascular risk factors who may derive the greatest benefit from targeted anti-inflammatory drugs., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MS is an employee of Alacris Theranostics GmbH., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background and Aims: Elevated triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) define a specific lipid profile associated with residual coronary artery disease (CAD) risk independently of total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels. Aim of the present study was to assess whether TG/HDL-C ratio, coronary atherosclerosis and their change over time are characterized by a specific lipidomic profiling in stable patients with chronic coronary syndrome (CCS)., Methods: TG/HDL-C ratio was calculated in 193 patients (57.8 ± 7.6 years, 115 males) with CCS characterized by clinical, bio-humoral profiles and cardiac imaging. Patient-specific plasma targeted lipidomics was defined through a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) strategy. Patients underwent coronary computed tomography angiography (CTA) and an individual CTA risk score, combining extent, severity, composition, and location of plaques, was calculated. All patients entered a follow-up (6.39 ± 1.17 years), including clinical, lipidomics and coronary CTA assessments., Results: Patients were divided in groups according to baseline TG/HDL-C quartiles: IQ (<1.391), IIQ (1.392-2.000), IIIQ (2.001-3.286), and IVQ (≥3.287). A specific pattern of altered lipids, characterized by reduced plasma levels of cholesterol esters, phosphatidylcholines and sphingomyelins, was associated with higher TG/HDL-C both at baseline and follow-up (IVQ vs IQ). The CTA risk score increased over time and this lipid signature was also associated with higher CTA score at follow-up., Conclusions: In stable CCS, a specific lipidomic signature identifies those patients with higher TG/HDL- C ratio and higher CTA score over time, suggesting possible molecular pathways of residual CAD risk not tackled by current optimal medical treatments., (Copyright © 2021 Elsevier B.V. All rights reserved.)

We assessed whether high triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) levels, expressed by an increased TG/HDL-C ratio, predict coronary atherosclerotic disease (CAD) outcomes in patients with stable angina. We studied 355 patients (60 ± 9 years, 211 males) with stable angina who underwent coronary computed tomography angiography (CTA), were managed clinically and followed for 4.5 ± 0.9 years. The primary composite outcome was all-cause mortality and non-fatal myocardial infarction. At baseline, the proportion of males, patients with metabolic syndrome, diabetes and obstructive CAD increased across TG/HDL-C ratio quartiles, together with markers of insulin resistance, hepatic and adipose tissue dysfunction and myocardial damage, with no difference in total cholesterol or LDL-C. At follow-up, the global CTA risk score (HR 1.06, 95% confidence interval (CI) 1.03-1.09, P = 0.001) and the IV quartile of the TG/HDL-C ratio (HR 2.85, 95% CI 1.30-6.26, P < 0.01) were the only independent predictors of the primary outcome. The TG/HDL-C ratio and the CTA risk score progressed over time despite increased use of lipid-lowering drugs and reduction in LDL-C. In patients with stable angina, high TG and low HDL-C levels are associated with CAD related outcomes independently of LDL-C and treatments.Trial registration. EVINCI study: ClinicalTrials.gov NCT00979199, registered September 17, 2009; SMARTool study: ClinicalTrials.gov NCT04448691, registered June 26, 2020., (© 2021. The Author(s).)

Objective: Externally validated pretest probability models for risk stratification of subjects with chest pain and suspected stable coronary artery disease (CAD), determined through invasive coronary angiography or coronary CT angiography, are analysed to characterise the best validation procedures in terms of discriminatory ability, predictive variables and method completeness., Design: Systematic review and meta-analysis., Data Sources: Global Health (Ovid), Healthstar (Ovid) and MEDLINE (Ovid) searched on 22 April 2020., Eligibility Criteria: We included studies validating pretest models for the first-line assessment of patients with chest pain and suspected stable CAD. Reasons for exclusion: acute coronary syndrome, unstable chest pain, a history of myocardial infarction or previous revascularisation; models referring to diagnostic procedures different from the usual practices of the first-line assessment; univariable models; lack of quantitative discrimination capability., Methods: Eligibility screening and review were performed independently by all the authors. Disagreements were resolved by consensus among all the authors. The quality assessment of studies conforms to the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). A random effects meta-analysis of area under the receiver operating characteristic curve (AUC) values for each validated model was performed., Results: 27 studies were included for a total of 15 models. Besides age, sex and symptom typicality, other risk factors are smoking, hypertension, diabetes mellitus and dyslipidaemia. Only one model considers genetic profile. AUC values range from 0.51 to 0.81. Significant heterogeneity (p<0.003) was found in all but two cases (p>0.12). Values of I 2 >90% for most analyses and not significant meta-regression results undermined relevant interpretations. A detailed discussion of individual results was then carried out., Conclusions: We recommend a clearer statement of endpoints, their consistent measurement both in the derivation and validation phases, more comprehensive validation analyses and the enhancement of threshold validations to assess the effects of pretest models on clinical management., Prospero Registration Number: CRD42019139388., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Long-term data on sex-differences in coronary plaque changes over time is lacking in a low-to-intermediate risk population of stable coronary artery disease (CAD). The aim of this study was to evaluate the role of sex on long-term plaque progression and evolution of plaque composition. Furthermore, the influence of menopause on plaque progression and composition was also evaluated. Patients that underwent a coronary computed tomography angiography (CTA) were prospectively included to undergo a follow-up coronary CTA. Total and compositional plaque volumes were normalized using the vessel volume to calculate a percentage atheroma volume (PAV). To investigate the influence of menopause on plaque progression, patients were divided into two groups, under and over 55 years of age. In total, 211 patients were included in this analysis, 146 (69%) men. The mean interscan period between baseline and follow-up coronary CTA was 6.2 ± 1.4 years. Women were older, had higher HDL levels and presented more often with atypical chest pain. Men had 434 plaque sites and women 156. On a per-lesion analysis, women had less fibro-fatty PAV compared to men (β -1.3 ± 0.4%; p < 0.001), with no other significant differences. When stratifying patients by 55 years age threshold, fibro-fatty PAV remained higher in men in both age groups (p < 0.05) whilst women younger than 55 years demonstrated more regression of fibrous (β -0.8 ± 0.3% per year; p = 0.002) and non-calcified PAV (β -0.7 ± 0.3% per year; p = 0.027). In a low-to-intermediate risk population of stable CAD patients, no significant sex differences in total PAV increase over time were observed. Fibro-fatty PAV was lower in women at any age and women under 55 years demonstrated significantly greater reduction in fibrous and non-calcified PAV over time compared to age-matched men. (ClinicalTrials.gov number, NCT04448691.)., (© 2021. The Author(s).)

Aims: To investigate the prognostic relevance of coronary anatomy, coronary function, and early revascularization in patients with stable coronary artery disease (CAD)., Methods and Results: From March 2009 to June 2012, 430 patients with suspected CAD (61 ± 9 years, 62% men) underwent coronary anatomical imaging by computed tomography coronary angiography (CTCA) and coronary functional imaging followed by invasive coronary angiography (ICA) if at least one non-invasive test was abnormal. Obstructive CAD was documented by ICA in 119 patients and 90 were revascularized within 90 days of enrolment. Core laboratory analysis showed that 134 patients had obstructive CAD by CTCA (>50% stenosis in major coronary vessels) and 79 significant ischaemia by functional imaging [>10% left ventricular (LV) myocardium]. Over mean follow-up of 4.4 years, major adverse events (AEs) (all-cause death, non-fatal myocardial infarction, or hospital admission for unstable angina or heart failure) or AEs plus late revascularization (LR) occurred in 40 (9.3%) and 58 (13.5%) patients, respectively. Obstructive CAD at CTCA was the only independent imaging predictor of AEs [hazard ratio (HR) 3.2, 95% confidence interval (CI) 1.10-9.30; P = 0.033] and AEs plus LR (HR 4.3, 95% CI 1.56-11.81; P = 0.005). Patients with CAD in whom early revascularization was performed in the presence of ischaemia and deferred in its absence had fewer AEs, similar to patients without CAD (HR 2.0, 95% CI 0.71-5.51; P = 0.195)., Conclusion: Obstructive CAD imaged by CTCA is an independent predictor of clinical outcome. Early management of CAD targeted to the combined anatomical and functional disease phenotype improves clinical outcome., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background Progression of coronary artery disease using serial coronary computed tomography angiography (CTA) is of clinical interest. Our primary aim was to prospectively assess the impact of clinical characteristics and statin use on quantitatively assessed coronary plaque progression in a low-risk study population during long-term follow-up. Methods Patients who previously underwent coronary CTA for suspected coronary artery disease were prospectively included to undergo follow-up coronary CTA. The primary end point was coronary artery disease progression, defined as the absolute annual increase in total, calcified, and noncalcified plaque volume by quantitative CTA analysis. Results In total, 202 patients underwent serial coronary CTA with a mean interscan period of 6.2±1.4 years. On a per-plaque basis, increasing age (β=0.070; P =0.058) and hypertension (β=1.380; P =0.075) were nonsignificantly associated with annual total plaque progression. Male sex (β=1.676; P =0.009), diabetes mellitus (β=1.725; P =0.012), and statin use (β=1.498; P =0.046) showed an independent association with annual progression of calcified plaque. While hypertension (β=2.259; P =0.015) was an independent determinant of noncalcified plaque progression, statin use (β=-2.178; P =0.050) was borderline significantly associated with a reduced progression of noncalcified plaque. Conclusions Statin use was associated with an increased progression of calcified coronary plaque and a reduced progression of noncalcified coronary plaque, potentially reflecting calcification of the noncalcified plaque component. Whereas hypertension was the only modifiable risk factor predictive of noncalcified plaque progression, diabetes mellitus mainly led to an increase in calcified plaque. These findings could yield the need for intensified preventive treatment of patients with diabetes mellitus and hypertension to slow and stabilize coronary artery disease progression and improve clinical outcome.

Aim: This study aimed at evaluating the cost-effectiveness of different non-invasive imaging-guided strategies for the diagnosis of obstructive coronary artery disease (CAD) in a European population of patients from the Evaluation of Integrated Cardiac Imaging in Ischemic Heart Disease (EVINCI) study., Methods and Results: Cost-effectiveness analysis was performed in 350 patients (209 males, mean age 59 ± 9 years) with symptoms of suspected stable CAD undergoing computed tomography coronary angiography (CTCA) and at least one cardiac imaging stress-test prior to invasive coronary angiography (ICA) and in whom imaging exams were analysed at dedicated core laboratories. Stand-alone stress-tests or combined non-invasive strategies, when the first exam was uncertain, were compared. The diagnostic end-point was obstructive CAD defined as > 50% stenosis at quantitative ICA in the left main or at least one major coronary vessel. Effectiveness was defined as the percentage of correct diagnosis (cd) and costs were calculated using country-specific reimbursements. Incremental cost-effectiveness ratios (ICERs) were obtained using per-patient data and considering "no-imaging" as reference. The overall prevalence of obstructive CAD was 28%. Strategies combining CTCA followed by stress ECHO, SPECT, PET, or stress CMR followed by CTCA, were all cost-effective. ICERs values indicated cost saving from - 969€/cd for CMR-CTCA to - 1490€/cd for CTCA-PET, - 3092€/cd for CTCA-SPECT and - 3776€/cd for CTCA-ECHO. Similarly when considering early revascularization as effectiveness measure., Conclusion: In patients with suspected stable CAD and low prevalence of disease, combined non-invasive strategies with CTCA and stress-imaging are cost-effective as gatekeepers to ICA and to select candidates for early revascularization.

Objective: Aim of this study was to evaluate the relationship of plasma PCSK9 with metabolic and inflammatory profile and coronary atherosclerotic burden in patients with suspected CAD enrolled in the EVINCI study., Methods: PCSK9 was measured in 539 patients (60.3 ± 8.6 years, 256 males) with symptoms of CAD characterized by risk factors, bio-humoral profiles, and treatment. N = 412 patients underwent coronary computed tomography angiography (CTA) to assess the presence and characteristics of coronary atherosclerosis. A CTA score, combining extent, severity, composition, and location of plaques was computed., Results: Patients were divided according to PCSK9 quartiles: I (< 136 ng/mL), II-III (136-266 ng/mL), and IV quartile (> 266 ng/mL). Compared with patients in quartile IV, patients in quartile I had a higher prevalence of the metabolic syndrome and higher values of body mass index. LDL- and HDL-cholesterol were significantly lower in patients in the quartile I than in those in quartile IV. Coronary CTA documented normal vessels in 30% and obstructive CAD in 35% of cases without differences among PCSK9 quartiles. Compared with patients with the highest levels, patients with the lowest PCSK9 levels had a higher CTA score mainly due to higher number of mixed non-obstructive coronary plaques. At multivariable analysis including clinical, medications, and lipid variables, PCSK9 was an independent predictor of the CTA score (coefficient - 0.129, SE 0.03, P < 0.0001), together with age, male gender, statins, interleukin-6, and leptin., Conclusion: In patients with stable CAD, low PCSK9 plasma levels are associated with a particular metabolic phenotype (low HDL cholesterol, the metabolic syndrome, obesity, insulin resistance and diabetes) and diffuse non-obstructive coronary atherosclerosis. Trial registration ClinicalTrials.gov NCT00979199. Registered September 17, 2009.

Aims: Hybrid imaging provides a non-invasive assessment of coronary anatomy and myocardial perfusion. We sought to evaluate the added clinical value of hybrid imaging in a multi-centre multi-vendor setting., Methods and Results: Fourteen centres enrolled 252 patients with stable angina and intermediate (20-90%) pre-test likelihood of coronary artery disease (CAD) who underwent myocardial perfusion scintigraphy (MPS), CT coronary angiography (CTCA), and quantitative coronary angiography (QCA) with fractional flow reserve (FFR). Hybrid MPS/CTCA images were obtained by 3D image fusion. Blinded core-lab analyses were performed for CTCA, MPS, QCA and hybrid datasets. Hemodynamically significant CAD was ruled-in non-invasively in the presence of a matched finding (myocardial perfusion defect co-localized with stenosed coronary artery) and ruled-out with normal findings (both CTCA and MPS normal). Overall prevalence of significant CAD on QCA (>70% stenosis or 30-70% with FFR≤0.80) was 37%. Of 1004 pathological myocardial segments on MPS, 246 (25%) were reclassified from their standard coronary distribution to another territory by hybrid imaging. In this respect, in 45/252 (18%) patients, hybrid imaging reassigned an entire perfusion defect to another coronary territory, changing the final diagnosis in 42% of the cases. Hybrid imaging allowed non-invasive CAD rule-out in 41%, and rule-in in 24% of patients, with a negative and positive predictive value of 88% and 87%, respectively., Conclusion: In patients at intermediate risk of CAD, hybrid imaging allows non-invasive co-localization of myocardial perfusion defects and subtending coronary arteries, impacting clinical decision-making in almost one every five subjects., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Objective: Circulating levels of high-sensitivity cardiac troponin T (hs-cTnT) and N terminal pro brain natriuretic peptide (NT-proBNP) are predictors of prognosis in patients with coronary artery disease (CAD). We aimed at evaluating the effect of coronary atherosclerosis and myocardial ischemia on cardiac release of hs-cTnT and NT-proBNP in patients with suspected CAD., Approach and Results: Hs-cTnT and NT-proBNP were measured in 378 patients (60.1±0.5 years, 229 males) with stable angina and unknown CAD enrolled in the Evaluation of Integrated Cardiac Imaging (EVINCI) study. All patients underwent stress imaging to detect myocardial ischemia and coronary computed tomographic angiography to assess the presence and characteristics of CAD. An individual computed tomographic angiography score was calculated combining extent, severity, composition, and location of plaques. In the whole population, the median (25-75 percentiles) value of plasma hs-cTnT was 6.17 (4.2-9.1) ng/L and of NT-proBNP was 61.66 (31.2-132.6) ng/L. In a multivariate model, computed tomographic angiography score was an independent predictor of the plasma hs-cTnT (coefficient 0.06, SE 0.02; P=0.0089), whereas ischemia was a predictor of NT-proBNP (coefficient 0.38, SE 0.12; P=0.0015). Hs-cTnT concentrations were significantly increased in patients with CAD with or without myocardial ischemia (P<0.005), whereas only patients with CAD and ischemia showed significantly higher levels of NT-proBNP (P<0.001)., Conclusions: In patients with stable angina, the presence and extent of coronary atherosclerosis is related with circulating levels of hs-cTnT, also in the absence of ischemia, suggesting an ischemia-independent mechanism of hs-cTnT release. Obstructive CAD causing myocardial ischemia is associated with increased levels of NT-proBNP., (© 2016 American Heart Association, Inc.)

We aimed to evaluate how chest pain categorization, currently used to assess the pretest probability of coronary artery disease (CAD), predicts the actual presence of CAD in a population of patients with stable symptoms. We studied 475 consecutive patients enrolled in the Evaluation of Integrated Cardiac Imaging for the Detection and Characterization of Ischemic Heart Disease study based on possible symptoms of CAD. Chest pain or discomfort was categorized as typical angina, atypical angina, or as nonanginal according to the guidelines. Exertional dyspnea and fatigue suspected to be angina equivalents were classified as atypical angina. Patients with a probability of CAD <20 or >90% based on age, gender, and symptoms were excluded. The end points of this substudy were significant CAD (defined by invasive coronary angiography as >50% reduction in lumen diameter in the left main stem or >70% stenosis in a major coronary vessel or 30% to 70% stenosis with fractional flow reserve ≤0.8), inducible myocardial ischemia at noninvasive stress imaging, and their association. Patients' symptoms had limited ability to predict the presence of significant CAD, global chi-square being 5.0. The inclusion of age increased global chi-square to 18.7 and gender increased it further to 51.1. Using inducible myocardial ischemia or the association of CAD with inducible ischemia as end points, the ability to predict these end points was again better for patient demographics than for patient symptoms. Thus, the ability of current models based on symptoms, age, and gender to predict the presence of CAD is mainly based on patient demographics as opposed to symptoms., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: Coronary computed tomography angiography (CTA) describes several features of coronary plaques, i.e. location, severity, and composition. Integrated CTA scores are able to identify individual patterns of higher risk. We sought to test whether circulating biomarkers related with metabolism and inflammation could predict high risk coronary anatomy at CTA in patients with stable chest pain., Methods: We evaluated a panel of 17 biomarkers in 429 patients (60.3 ± 0.4 years, 268 males) with stable chest pain who underwent coronary CTA having been enrolled in the Evaluation of Integrated Cardiac Imaging (EVINCI) study. The individual CTA risk score was calculated combining plaque extent, severity, composition, and location. The presence and distribution of non-calcified, mixed and calcified plaques were analyzed in each patient., Results: After adjustment for age, sex and medical treatment, high-density lipoprotein (HDL) cholesterol, leptin, and interleukin-6 (IL-6) were independent predictors of CTA risk score at multivariate analysis (P = 0.050, 0.002, and 0.007, respectively). Integrating these biomarkers with common clinical variables, a model was developed which showed a better discriminating ability than the Framingham Risk Score and the Euro-SCORE in identifying the patients with higher CTA risk score (area under the receiver-operating characteristics curve = 0.81, 0.63 and 0.71, respectively, P < 0.001). These three biomarkers were significantly altered in patients with mixed or non-calcified plaques., Conclusions: In patients with stable chest pain, low HDL cholesterol, low leptin and high IL-6 are independent predictors of high risk coronary anatomy as defined by an integrated CTA risk score., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: The choice of imaging techniques in patients with suspected coronary artery disease (CAD) varies between countries, regions, and hospitals. This prospective, multicenter, comparative effectiveness study was designed to assess the relative accuracy of commonly used imaging techniques for identifying patients with significant CAD., Methods and Results: A total of 475 patients with stable chest pain and intermediate likelihood of CAD underwent coronary computed tomographic angiography and stress myocardial perfusion imaging by single photon emission computed tomography or positron emission tomography, and ventricular wall motion imaging by stress echocardiography or cardiac magnetic resonance. If ≥1 test was abnormal, patients underwent invasive coronary angiography. Significant CAD was defined by invasive coronary angiography as >50% stenosis of the left main stem, >70% stenosis in a major coronary vessel, or 30% to 70% stenosis with fractional flow reserve ≤0.8. Significant CAD was present in 29% of patients. In a patient-based analysis, coronary computed tomographic angiography had the highest diagnostic accuracy, the area under the receiver operating characteristics curve being 0.91 (95% confidence interval, 0.88-0.94), sensitivity being 91%, and specificity being 92%. Myocardial perfusion imaging had good diagnostic accuracy (area under the curve, 0.74; confidence interval, 0.69-0.78), sensitivity 74%, and specificity 73%. Wall motion imaging had similar accuracy (area under the curve, 0.70; confidence interval, 0.65-0.75) but lower sensitivity (49%, P<0.001) and higher specificity (92%, P<0.001). The diagnostic accuracy of myocardial perfusion imaging and wall motion imaging were lower than that of coronary computed tomographic angiography (P<0.001)., Conclusions: In a multicenter European population of patients with stable chest pain and low prevalence of CAD, coronary computed tomographic angiography is more accurate than noninvasive functional testing for detecting significant CAD defined invasively., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT00979199., (© 2015 American Heart Association, Inc.)

Reduced plasma adiponectin has been associated with abnormal lipid profile, reduced left ventricle (LV) function, and the extent of coronary atherosclerosis in coronary artery disease. The aim of this study was to assess these relationships in patients with dilated cardiomyopathy (DCM) without overt heart failure. Plasma adiponectin was measured in 55 DCM patients (age, 59 ± 12 years; male, 36; body mass index [BMI], 26.9 ± 0.49 kg/m²; LV ejection fraction, 39.8% ± 1.3%; New York Heart Association class I-II) and in 40 age- and BMI-matched healthy controls. In a subset of 25 patients, myocardial blood flow (MBF) was measured at rest and during intravenous dipyridamole (0.56 mg/kg in 4 minutes) by positron emission tomography and ¹³N-ammonia as a flow tracer. Adiponectin was 6.6 ± 0.34 μg/mL in controls and 10.9 ± 0.85 μg/mL in DCM patients (P < .001), where it was related inversely with BMI (P = .009) and directly with brain natriuretic peptide (P = .017), high-density lipoprotein (HDL) cholesterol (P = .002), and MBF dipyridamole (P = .020). Adiponectin lesser than median value in patients was associated with higher total to HDL cholesterol ratio (4.8 ± 0.24 vs 3.9 ± 0.18, P = .009) and lower MBF reserve (1.76 ± 0.16 vs 2.43 ± 0.19, P = .01). These results could suggest that down-regulation of the adiponectin levels and reduced HDL cholesterol have a key role in causing impaired coronary function and myocardial perfusion in DCM., (© 2011 Elsevier Inc. All rights reserved.)