Coronary Artery Plaque Phenotype and 5-Year Clinical Outcomes in Older Patients with Non-ST Elevation Acute Coronary Syndrome.

Background: Lesions with thin-cap fibroatheroma (TCFA), small luminal area and large plaque burden (PB) have been considered at high risk of cardiovascular events. Older patients were not represented in studies which demonstrated correlation between clinical outcome and plaque characteristics. This study aims to investigate the prognostic role of high-risk plaque characteristics and long-term outcome in older patients presenting with non-ST elevation acute coronary syndrome (NSTEACS). Methods: This study recruited older patients aged ≥ 75 years with NSTEACS undergoing virtual-histology intravascular ultrasound (VH-IVUS) imaging from the Improve Clinical Outcomes in high-risk patieNts with acute coronary syndrome (ICON-1). Primary endpoint was the composite of major adverse cardiovascular events (MACE) consisting of all-cause mortality, myocardial infarction (MI), and any revascularisation. Every component of MACE and target vessel failure (TVF) including MI and any revascularisation were considered as secondary endpoints. Results: Eighty-six patients with 225 vessels undergoing VH-IVUS at baseline completed 5-year clinical follow-up. Patients with minimal lumen area (MLA) ≤ 4 mm 2 demonstrated increased risk of MACE (hazard ratio [HR] 2.37, 95% confidence interval [CI] 1.00-5.59, p = 0.048) with a worse event-free survival (Log Rank 4.17, p = 0.041) than patients with MLA > 4 mm 2 . Patients with combination of TCFA, MLA ≤ 4 mm 2 and PB ≥ 70% showed high risk of MI (HR 5.23, 95% CI 1.05-25.9, p = 0.043). Lesions with MLA ≤ 4 mm 2 had 6-fold risk of TVF (HR 6.16, 95% CI 1.24-30.5, p = 0.026). Conclusions: Small luminal area appears as the major prognostic factor in older patients with NSTEACS at long-term follow-up. Combination of TCFA, MLA ≤ 4 mm 2 and PB ≥ 70% was associated with high risk of MI. Clinical Trial Registration: NCT01933581.

Epicardial and pericoronary adipose tissue and coronary plaque burden in patients with Cushing's syndrome: a propensity score-matched study.

PURPOSE: To assess coronary inflammation by measuring the volume and density of the epicardial adipose tissue (EAT), perivascular fat attenuation index (FAI) and coronary plaque burden in patients with Cushing's syndrome (CS) based on coronary computed tomography angiography (CCTA). METHODS: This study included 29 patients with CS and 58 matched patients without CS who underwent CCTA. The EAT volume, EAT density, FAI and coronary plaque burden were measured. The high-risk plaque (HRP) was also evaluated. CS duration from diagnosis, 24-h urinary free cortisol (UFC), and abdominal visceral adipose tissue volume (VAT) of CS patients were recorded. RESULTS: The CS group had higher EAT volume (146.9 [115.4, 184.2] vs. 119.6 [69.0, 147.1] mL, P = 0.006), lower EAT density (- 78.79 ± 5.89 vs. - 75.98 ± 6.03 HU, P = 0.042), lower FAI (- 84.0 ± 8.92 vs. - 79.40 ± 10.04 HU, P = 0.038), higher total plaque volume (88.81 [36.26, 522.5] vs. 44.45 [0, 198.16] mL, P = 0.010) and more HRP plaques (7.3% vs. 1.8%, P = 0.026) than the controls. The multivariate analysis suggested that CS itself (ß [95% CI], 29.233 [10.436, 48.03], P = 0.014), CS duration (ß [95% CI], 0.176 [0.185, 4.242], P = 0.033), and UFC (ß [95% CI], 0.197 [1.803, 19.719], P = 0.019) were strongly associated with EAT volume but not EAT density, and EAT volume (ß [95% CI] - 0.037[- 0.058, - 0.016], P = 0.001) not CS was strongly associated with EAT density. EAT volume, FAI and plaque burden increased (all P < 0.05) in 6 CS patients with follow-up CCTA. The EAT volume had a moderate correlation with abdominal VAT volume (r = 0.526, P = 0.008) in CS patients. CONCLUSIONS: Patients with CS have higher EAT volume and coronary plaque burden but less inflammation as detected by EAT density and FAI. The EAT density is associated with EAT volume but not CS itself.

Does Coronary Plaque Morphology Matter Beyond Plaque Burden?

PURPOSE OF REVIEW: Imaging of adverse coronary plaque features by coronary computed tomography angiography (CCTA) has advanced greatly and at a fast pace. We aim to describe the evolution, present and future in plaque analysis, and its value in comparison to plaque burden. RECENT FINDINGS: Recently, it has been demonstrated that in addition to plaque burden, quantitative and qualitative assessment of coronary plaque by CCTA can improve the prediction of future major adverse cardiovascular events in diverse coronary artery disease scenarios. The detection of high-risk non-obstructive coronary plaque can lead to higher use of preventive medical therapies such as statins and aspirin, help identify culprit plaque, and differentiate between myocardial infarction types. Even more, over traditional plaque burden, plaque analysis including pericoronary inflammation can potentially be useful tools for tracking disease progression and response to medical therapy. The identification of the higher risk phenotypes with plaque burden, plaque characteristics, or ideally both can allow the allocation of targeted therapies and potentially monitor response. Further observational data are now required to investigate these key issues in diverse populations, followed by rigorous randomized controlled trials.

Association of serum cystatin C level with coronary atherosclerotic plaque burden: a comprehensive analysis of observational studies and genetic study.

BACKGROUND AND AIMS: Epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. However, the relationship between serum cystatin C level and coronary atherosclerotic plaque burden is limited. We aimed to evaluate the relationship between circulating cystatin C and coronary atherosclerotic plaque burden. METHODS: This study was a cross-sectional study based on China community population. Measurements of plaque burden were based on the segment-involvement score (SIS) and segment stenosis score (SSS), which derived from the Coronary Artery Tree Model Depicting Coronary Artery Plaque Scores. Logistic regression model was used to demonstrate the association between cystatin C level and coronary artery plaque burden. Mendelian randomization (MR) analyses were conducted to assess the causal effect of cystatin C level on coronary atherosclerosis risk. RESULTS: A total of 3,043 objects were included in the present study. The odds risks (OR) of severe plaque burden in the highest serum cystatin C levels (OR: 2.50; Cl:1.59-3.91; P < 0.001) and medium-level cystatin C levels (OR: 1.86; 95% Cl: 1.21-2.88; P = 0.005) were significantly higher after fulled adjusted confounders compared with the lowest levels of serum cystatin C by SSS. The MR analysis showed that genetic predicted cystatin C levels was associated with an increased risk of coronary atherosclerosis (OR, 1.004; 95% CI, 1.002-1.006, P < 0.001) . CONCLUSION: Elevated serum cystatin C levels were associated with coronary atherosclerotic plaque burden. Cystatin C levels had a causal effect on an increased risk of coronary atherosclerosis at the genetic level. WHAT IS ALREADY KNOWN ON THIS TOPIC?: Coronary artery disease is currently the most common cardiovascular disease and the leading global cause of mortality. Previous studies reported that higher serum cystatin C levels were associated with an increased risk for future cardiovascular events, independent of the normal creatinine levels or estimated glomerular filtration rate (eGFR) values. The presence of high-risk coronary atherosclerotic plaque burden is associated with increased risk of cardiovascular events. However, the association between serum cystatin C and coronary atherosclerotic plaque burden is not very clear. WHAT THIS STUDY ADDS?: Our study demonstrated that the elevated serum cystatin C levels were associated with coronary atherosclerotic plaque burden. In addition, we found that serum cystatin C levels had a causal effect on an increased risk of coronary atherosclerosis at the genetic level. HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY?: Current research finds that serum cystatin C levels were associated with coronary atherosclerosis. The metabolic pathway of cystatin C could be a target for new therapies against CAD.

High-field magnetic resonance microscopy of aortic plaques in a mouse model of atherosclerosis.

OBJECTIVES: Pre-clinical models of human atherosclerosis are extensively used; however, traditional histological methods do not allow for a holistic view of vascular lesions. We describe an ex-vivo, high-resolution MRI method that allows the 3 dimensional imaging of the vessel for aortic plaque visualization and quantification. MATERIALS AND METHODS: Aortas from apolipoprotein-E-deficient (apoE-/-) mice fed an atherogenic diet (group 1) or a control diet (group 2) were subjected to 14 T MR imaging using a 3D gradient echo sequence. The obtained data sets were reconstructed (Matlab), segmented, and analyzed (Avizo). The aortas were further sectioned and subjected to traditional histological analysis (Oil-Red O and hematoxylin staining) for comparison. RESULTS: A resolution up to 15 × 10x10 µm3 revealed that plaque burden (mm3) was significantly (p < 0.05) higher in group 1 (0.41 ± 0.25, n = 4) than in group 2 (0.01 ± 0.01, n = 3). The achieved resolution provided similar detail on the plaque and the vessel wall morphology compared with histology. Digital image segmentation of the aorta's lumen, plaque, and wall offered three-dimensional visualizations of the entire, intact aortas. DISCUSSION: 14 T MR microscopy provided histology-like details of pathologically relevant vascular lesions. This work may provide the path research needs to take to enable plaque characterization in clinical applications.

Combinatorial model of amyloid ß and tau reveals synergy between amyloid deposits and tangle formation.

AIMS: To illuminate the pathological synergy between Aß and tau leading to emergence of neurofibrillary tangles (NFT) in Alzheimer's disease (AD), here, we have performed a comparative neuropathological study utilising three distinctive variants of human tau (WT tau, P301L mutant tau and S320F mutant tau). Previously, in non-transgenic mice, we showed that WT tau or P301L tau does not form NFT while S320F tau can spontaneously aggregate into NFT, allowing us to test the selective vulnerability of these different tau conformations to the presence of Aß plaques. METHODS: We injected recombinant AAV-tau constructs into neonatal APP transgenic TgCRND8 mice or into 3-month-old TgCRND8 mice; both cohorts were aged 3 months post injection. This allowed us to test how different tau variants synergise with soluble forms of Aß (pre-deposit cohort) or with frank Aß deposits (post-deposit cohort). RESULTS: Expression of WT tau did not produce NFT or altered Aß in either cohort. In the pre-deposit cohort, S320F tau induced Aß plaque deposition, neuroinflammation and synaptic abnormalities, suggesting that early tau tangles affect the amyloid cascade. In the post-deposit cohort, contemporaneous expression of S320F tau did not exacerbate amyloid pathology, showing a dichotomy in Aß-tau synergy based on the nature of Aß. P301L tau produced NFT-type inclusions in the post-deposit cohort, but not in the pre-deposit cohort, indicating pathological synergy with pre-existing Aß deposits. CONCLUSIONS: Our data show that different tau mutations representing specific folding variants of tau synergise with Aß to different extents, depending on the presence of cerebral deposits.

Management of Patients with Embolic Stroke of Unknown Source: Interpreting the Evidence in the Light of Clinical Judgement.

PURPOSE OF REVIEW: To assess the validity of the belief that anticoagulation is not beneficial in patients with embolic stroke of unknown source (ESUS), and to asssess the benefits and safety of direct-acting oral anticoagulants (DOACs). RECENT FINDINGS: The failure of randomized trials to show benefit of anticoagulation in ESUS is probably due to misclassification of large artery atherosclerosis (LAA) as ESUS, as defined by a stenosis ≥ 50%. There are important differences among DOACs. There are a number of problems with dabigatran, and rivaroxaban and edoxaban are not suitable for once-daily dosing. Recent evidence from real-world practice indicates that apixaban is more effective and safer than rivaroxaban. Plaque burden should be included in the definition of LAA. Patients in whom a cardioembolic source is strongly suspected should be anticoagulated; antiplatelet agents are not significantly safer than DOACs, and are not effective in cardioembolic stroke.

Neutrophil-lymphocyte ratio and carotid plaque burden in patients with essential thrombocythemia and polycythemia vera.

BACKGROUND AND AIMS: Chronic inflammation plays a critical role in the pathogenesis of myeloproliferative neoplasm (MPN), and inflammatory conditions are closely related to the development and exacerbation of atherosclerosis. This study aimed to compare carotid plaque burden and neutrophil-lymphocyte ratio (NLR) in the essential thrombocythemia (ET)/polycythemia vera (PV) and control groups. METHODS AND RESULTS: We retrospectively assessed carotid plaque burden and NLR in patients with ET/PV between January 2010 and September 2021 and propensity-score matched these patients to control subjects from the general population. All patients underwent carotid imaging using carotid ultrasonography for atherosclerosis screening. After 3:1 propensity-score matching, 140 patients in the control group were matched to 51 patients in ET/PV group. The mean NLR was significantly higher in the MPN group than in the control group (4.77 ± 3.96 vs. 1.93 ± 1.03, p < 0.001). The carotid plaque score was also higher in MPN group than in the control group (2.37 ± 1.47 vs. 1.94 ± 1.17, p = 0.038). CONCLUSION: Patients with PV/ET show a higher NLR and carotid plaque burden than the normal population. This reflected that PV/ET was a highly inflammatory and atherosclerotic condition expressing potentially increased cardiovascular risk.

Coronary artery calcium burden, carotid atherosclerotic plaque burden, and myocardial blood flow in patients with end-stage renal disease: A non-invasive imaging study combining PET/CT and 3D ultrasound.

BACKGROUND: Imaging-based measures of atherosclerosis such as coronary artery calcium score (CACS) and coronary flow reserve (CFR) as well as carotid atherosclerotic plaque burden (cPB) are predictors of cardiovascular events in the general population. The objective of this study was to correlate CACS, cPB, myocardial blood flow (MBF), and CFR in patients with end-stage renal disease (ESRD). METHODS AND RESULTS: 39 patients (mean age 53 ± 12 years) with ESRD prior to kidney transplantation were enrolled. MBF and CFR were quantified at baseline and under hyperemia by 13N-NH3-PET/CT. CACS was calculated from low-dose CT scans acquired for PET attenuation correction. cPB was assessed by 3D ultrasound. Uni- and multivariate regression analyses between these and clinical parameters were performed. Median follow-up time for clinical events was 4.4 years. Kaplan-Meier survival estimates with log-rank test were performed with regards to cardiovascular (CV) events and death of any cause. CACS and cPB were associated in ESRD patients (r = 0.48; p ≤ 0.01). While cPB correlated with age (r = 0.43; p < 0.01), CACS did not. MBFstress was negatively associated with age (r = 0.44; p < 0.01) and time on dialysis (r = 0.42; p < 0.01). There were negative correlations between MBFstress and CACS (r = - 0.62; p < 0.001) and between MBFstress and cPB (r = - 0.43; p < 0.01). Age and CACS were the strongest predictors for MBFstress. CFR was impaired (< 2.0) in eight patients who also presented with higher cPB and higher CACS compared to those with a CFR > 2.0 (p = 0.06 and p = 0.4). In contrast to MBFstress, there was neither a significant correlation between CFR and CACS (r = - 0.2; p = 0.91) nor between CFR and cPB (r = - 0.1; p = 0.55). CV event-free survival was associated with reduced CFR and MBFstress (p = 0.001 and p < 0.001) but not with cPB or CACS. CONCLUSIONS: CACS, cPB, and MBFstress are associated in patients with ESRD. Atherosclerosis is earlier detected by MBFstress than by CFR. CV event-free survival is associated with impaired CFR and MBFstress.

Choosing between anatomy and function is not always evident for the heart of end-stage renal disease patients. How low can we go?

Patients with chronic kidney disease (CKD) are at a very high risk of adverse cardiovascular events. In CKD patients, vascular calcification is more prevalent, appears at an earlier age, and is more severe than in the general population. CKD physiology rather than the effects of dialysis is the primary driver of microvascular disease in these patients. Considering the significant morbidity and mortality attributable to cardiovascular disease in the CKD population, risk stratification remains an important challenge. Topics such as function vs anatomy to properly risk stratify these patients, as well as future perspectives on non-invasive techniques, will be addressed.

Diabetic microvascular complications are associated with reduced global longitudinal strain independent of atherosclerotic coronary artery disease in asymptomatic patients with diabetes mellitus: a cross-sectional study.

BACKGROUND: Reduced left ventricular function, assessed by global longitudinal strain (GLS), is sometimes observed in asymptomatic patients with diabetes mellitus (DM) and is often present in patients with diabetes-related microvascular complications. Our aim was to assess the association between microvascular complications, coronary artery plaque burden (PB) and GLS in asymptomatic patients with DM and non-obstructive coronary artery disease (CAD). METHODS: This cross-sectional study included patients with DM without any history, symptoms or objective evidence of obstructive CAD. All patients were identified in the outpatient Clinic of Endocrinology at Odense University Hospital Svendborg. An echocardiography and a coronary computed tomography angiography were performed to assess GLS and the degree of CAD, respectively. A coronary artery stenosis < 50% was considered non-obstructive. A linear regression model was used to evaluate the impact of potential confounders on GLS with adjustment of body mass index (BMI), mean arterial pressure (MAP), microvascular complications, type of diabetes, tissue Doppler average early diastolic mitral annulus velocity (e') and PB. RESULTS: Two hundred and twenty-two patients were included, of whom 172 (77%) had type 2 DM and 50 (23%) had type 1 diabetes. One hundred and eleven (50%) patients had microvascular complications. GLS decreased as the burden of microvascular complications increased (P-trend = 0.01): no microvascular complications, GLS (- 16.4 ± 2.5%), 1 microvascular complication (- 16.0 ± 2.5%) and 2-3 microvascular complications (- 14.9 ± 2.8%). The reduction in GLS remained significant after multivariable adjustment (ß 0.50 [95% CI 0.11-0.88], p = 0.01). BMI (ß 0.12 [95% CI 0.05-0.19]) and MAP (ß 0.05 [95% CI 0.01-0.08]) were associated with reduced GLS. In addition, an increased number of microvascular complications was associated with increased PB (ß 2.97 [95% CI 0.42-5.51], p = 0.02) in a univariable linear regression model, whereas there was no significant association between PB and GLS. CONCLUSIONS: The burden of microvascular complications was associated with reduced GLS independent of other cardiovascular risk factors in asymptomatic patients with DM and non-obstructive CAD. In addition, the burden of microvascular complications was associated with increasing PB, whereas PB was not associated with GLS.

Three Dimensional Carotid and Femoral Ultrasound is not Superior to Two Dimensional Ultrasound as a Predictor of Coronary Atherosclerosis Among Men With Intermediate Cardiovascular Risk.

BACKGROUND: Current cardiovascular disease (CVD) risk stratification scales, drawn up from traditional risk factors, have important limitations. The detection of subclinical atherosclerosis, by a non-invasive technique such as peripheral arteries ultrasound (US) may improve cardiovascular risk (CVR) stratification, especially in intermediate risk population. Our aim was to compare the predictive power of atherosclerotic plaques detected in carotid and femoral arteries by 2-dimensional (2D) vs. 3-dimensional (3D) US for positive coronary artery calcium score (CACS), used as a proxy for CVD, in a middle-aged sample with intermediate 10-year CVR (7.5-20%). METHODS: To detect atherosclerotic plaques by 2D vs. 3D US scan of carotid and femoral arteries and comparison of their association with CACS obtained by computed tomography (CT) of subjects with intermediate CVR belonging to the Aragon Workers' Health Study. RESULTS: 120 men were included, with a 10.4% average 10 years CVR. Forty-one (34.2%) participants had CACS ≥ 1. 90 participants (75%) had at least one plaque detected by 2D scan while 85 participants (70.8%) had at least a plaque detected by 3D US. Conventional CVR estimates c-statistic for CACS was .590. Although the variables most predicted of CACS ≥ 1 were those measured by 3D US (total plaque volume and mean of plaque density, c-statistics: .743 and .750 respectively), their predictive capacity was not statistically significantly different from the number of territories with plaque, measured either by 2D and 3D US (c-statistics .728 to .740 respectively). CONCLUSION: Subclinical atherosclerosis measured by 2D and 3D US were better predictors of CACS ≥ 1 than CVR estimated by conventional guidelines. In our sample, 3D US did not show any significant advantages with respect to 2D US for the prediction of coronary atherosclerosis.

The Relationship Between Obstructive Sleep Apnea and Coronary Plaque: A Coronary Computed Tomographic Angiography Study.

BACKGROUND: Coronary artery disease continues to be the most important cause of morbidity and mortality. Obstructive sleep apnea (OSA) is independently associated with subclinical atherosclerosis. In this study, we aimed to assess the relationship between the presence of coronary plaques and OSA and between coronary plaque burden and the severity of OSA according to plaque type. METHODS: In this cross-sectional study, we enrolled 214 consecutive patients who were divided into four groups of 43 patients (age: 52.3 ± 6.4 years) without OSA, 51 patients (age: 53.9 ± 6.7 years) with mild OSA, 40 patients (age: 55.2 ± 5.9 years) with moderate OSA, and 80 patients (age: 54.9 ± 7.2 years) with severe OSA according to the apnea-hypopnea index (AHI). We performed coronary computed tomographic angiography (CCTA) and evaluated plaque positivity, the presence of non-calcified/mixed plaques, and total stenosis score for each group. RESULTS: The prevalence of non-calcified/mixed plaques was three times higher in the severe OSA (41.3%) group and two times higher in the moderate OSA (30.0%) group compared to the patients without OSA (14.0%). When the four groups were examined in terms of plaque burden, the total stenosis score was found to increase with the presence and severity of OSA (0.27 ± 0.85, 1.07 ± 2.44, 1.75 ± 2.85, and 2.55 ± 3.96 respectively, p = 0.001). In addition, AHI and age were independent predictors of the presence of non-calcified/mixed plaques (p < 0.001 and p = 0.007, respectively). CONCLUSIONS: The presence of coronary artery plaques, especially non-calcified/mixed plaques, and coronary artery stenosis as measured by CCTA was significantly associated with the severity of sleep-disordered breathing in symptomatic patients at low to intermediate risk of coronary artery disease. Prospective studies are needed to establish the relationship between plaque burden and OSA.

Iterative Image Reconstruction Improves the Accuracy of Automated Plaque Burden Assessment in Coronary CT Angiography: A Comparison With Intravascular Ultrasound.

OBJECTIVE: The purpose of this study was to determine whether use of iterative image reconstruction algorithms improves the accuracy of coronary CT angiography (CCTA) compared with intravascular ultrasound (IVUS) in semiautomated plaque burden assessment. MATERIALS AND METHODS: CCTA and IVUS images of seven coronary arteries were acquired ex vivo. CT images were reconstructed with filtered back projection (FBP) and adaptive statistical (ASIR) and model-based (MBIR) iterative reconstruction algorithms. Cross-sectional images of the arteries were coregistered between CCTA and IVUS in 1-mm increments. In CCTA, fully automated (without manual corrections) and semiautomated (allowing manual corrections of vessel wall boundaries) plaque burden assessments were performed for each of the reconstruction algorithms with commercially available software. In IVUS, plaque burden was measured manually. Agreement between CCTA and IVUS was determined with Pearson correlation. RESULTS: A total of 173 corresponding cross sections were included. The mean plaque burden measured with IVUS was 63.39% ± 10.63%. With CCTA and the fully automated technique, it was 54.90% ± 11.70% with FBP, 53.34% ± 13.11% with ASIR, and 55.35% ± 12.22% with MBIR. With CCTA and the semiautomated technique mean plaque burden was 54.90% ± 11.76%, 53.40% ± 12.85%, 57.09% ± 11.05%. Manual correction of the semiautomated assessments was performed in 39% of all cross sections and improved plaque burden correlation with the IVUS assessment independently of reconstruction algorithm (p < 0.0001). Furthermore, MBIR was superior to FBP and ASIR independently of assessment method (semiautomated, r = 0.59 for FBP, r = 0.52 for ASIR, r = 0.78 for MBIR, all p < 0.001; fully automated, r = 0.40 for FBP, r = 0.37 for ASIR, r = 0.53 for MBIR, all p < 0.001). CONCLUSION: For the quantification of plaque burden with CCTA, MBIR led to better correlation with IVUS than did traditional reconstruction algorithms such as FBP, independently of the use of a fully automated or semiautomated assessment approach. The highest accuracy for quantifying plaque burden with CCTA can be achieved by using MBIR data with semiautomated assessment.

Association of Dyslipidemia and Sex With Coronary Artery Calcium Assessed by Coronary Computed Tomography Angiography.

Previous studies reporting that statin increases coronary artery calcium (CAC) were conducted exclusively on patients with statin as a prevention, regardless of the presence or absence of dyslipidemia. The impact of sex on CAC has not been fully evaluated. We aimed to determine the association of dyslipidemia and sex with CAC using 320-row multi-detector computed tomography (MDCT).Of the 356 consecutive patients who underwent coronary MDCT, 251 patients were enrolled, after excluding those with prior stenting and/or coronary bypass grafting or images showing motion artifacts. The primary outcome measures were the percent calcium volume (PCV) and percent atheroma volume (PAV) per coronary vessel.Multivariable analyses indicated that PCV was significantly higher in dyslipidemia patients without statins than in the subjects without dyslipidemia [partial regression coefficient (PRC): 2.59, 95% confidence interval (CI): 0.83 to 4.34, P = 0.004]. In contrast, PCV was similar in dyslipidemia patients taking statins and those without dyslipidemia (PRC: -1.09, 95% CI: -2.82 to 0.65, P = 0.22). There was no significant difference in PCV between men and women, although women exhibited a significantly lower PAV (PRC: -2.87, 95% CI: -4.54 to -1.20, P = 0.001).In low-risk patients, these results could be translated into hypotheses, which should be tested in future prospective studies. Furthermore, there was no significant difference in CAC between men and women, but women had lower PAV than men.

COPS5 protein overexpression increases amyloid plaque burden, decreases spinophilin-immunoreactive puncta, and exacerbates learning and memory deficits in the mouse brain.

Brain accumulation of neurotoxic amyloid ß (Aß) peptide because of increased processing of amyloid precursor protein (APP), resulting in loss of synapses and neurodegeneration, is central to the pathogenesis of Alzheimer disease (AD). Therefore, the identification of molecules that regulate Aß generation and those that cause synaptic damage is crucial for future therapeutic approaches for AD. We demonstrated previously that COPS5 regulates Aß generation in neuronal cell lines in a RanBP9-dependent manner. Consistent with the data from cell lines, even by 6 months, COPS5 overexpression in APΔE9 mice (APΔE9/COPS5-Tg) significantly increased Aß40 levels by 32% (p < 0.01) in the cortex and by 28% (p < 0.01) in the hippocampus, whereas the increases for Aß42 were 37% (p < 0.05) and 34% (p < 0.05), respectively. By 12 months, the increase was even more robust. Aß40 levels increased by 63% (p < 0.001) in the cortex and by 65% (p < 0.001) in the hippocampus. Similarly, Aß42 levels were increased by 69% (p < 0.001) in the cortex and by 71% (p < 0.011) in the hippocampus. Increased Aß levels were translated into an increased amyloid plaque burden both in the cortex (54%, p < 0.01) and hippocampus (64%, p < 0.01). Interestingly, COPS5 overexpression increased RanBP9 levels in the brain, which, in turn, led to increased amyloidogenic processing of APP, as reflected by increased levels of sAPPß and decreased levels of sAPPα. Furthermore, COPS5 overexpression reduced spinophilin in both the cortex (19%, p < 0.05) and the hippocampus (20%, p < 0.05), leading to significant deficits in learning and memory skills. Therefore, like RanBP9, COPS5 also plays a pivotal role in amyloid pathology in vivo.

An assessment on the incremental value of high-resolution magnetic resonance imaging to identify culprit plaques in atherosclerotic disease of the middle cerebral artery.

OBJECTIVE: Although certain morphological features depicted by high resolution, multi-contrast magnetic resonance imaging (hrMRI) have been shown to be different between culprit and non-culprit middle cerebral artery (MCA) atherosclerotic lesions, the incremental value of hrMRI to define culprit lesions over stenosis has not been assessed. METHODS: Patients suspected with MCA stenosis underwent hrMRI. Lumen and outer wall were segmented to calculate stenosis, plaque burden (PB), volume (PV), length (PL) and minimum luminal area (MLA). RESULTS: Data from 165 lesions (112 culprit and 53 non-culprit) in 139 individuals were included. Culprit lesions were larger and longer with a narrower lumen and increased PB compared with non-culprit lesions. More culprit lesions showed contrast enhancement. Both PB and MLA were better indicators than stenosis in differentiating lesion types (AUC were 0.649, 0.732 and 0.737 for stenosis, PB and MLA, respectively). Combinations of PB, MLA and stenosis could improve positive predictive value (PPV) and specificity significantly. An optimal combination of stenosis ≥ 50 %, PB ≥ 77 % and MLA ≤ 2.0 mm(2) produced a PPV = 85.7 %, negative predictive value = 54.1 %, sensitivity = 69.6 %, specificity = 75.5 %, and accuracy = 71.5 %. CONCLUSIONS: hrMRI plaque imaging provides incremental information to luminal stenosis in identifying culprit lesions. KEY POINTS: • High resolution MRI provides incremental information in defining culprit MCA atherosclerotic lesions. • Both plaque burden and minimum luminal area are better indicators than stenosis. • An optimal combination includes stenosis ≥ 50 %, PB ≥ 77 % and MLA ≤ 2.0 mm (2) .

Cholesterol efflux capacity in humans with psoriasis is inversely related to non-calcified burden of coronary atherosclerosis.

AIMS: Cholesterol efflux capacity (CEC) was recently shown to predict future cardiovascular (CV) events. Psoriasis both increases CV risk and impairs CEC. However, whether having poor CEC is associated with coronary plaque burden is currently unknown. We aimed to assess the cross-sectional relationship between coronary plaque burden assessed by quantitative coronary computed tomography angiography (CCTA) with CEC in a well-phenotyped psoriasis cohort. METHODS AND RESULTS: Total burden and non-calcified burden (NCB) plaque indices were assessed in 101 consecutive psoriasis patients using quantitative software. Cholesterol efflux capacity was quantified using a cell-based ex vivo assay measuring the ability of apoB-depleted plasma to mobilize cholesterol from lipid-loaded macrophages. Cholesterol efflux capacity was inversely correlated with NCB (unadjusted ß-coefficient -0.33; P < 0.001), and this relationship persisted after adjustment for CV risk factors (ß -0.24; P < 0.001), HDL-C levels (ß -0.22; P < 0.001), and apoA1 levels (ß -0.19; P < 0.001). Finally, we observed a significant gender interaction (P < 0.001) whereby women with low CEC had higher NCB compared to men with low CEC. CONCLUSIONS: We show that CEC is inversely associated with prevalent coronary plaque burden measured by quantitative CCTA. Low CEC may therefore be an important biomarker for subclinical coronary atherosclerosis in psoriasis. CLINICALTRIALSGOV: NCT01778569.

Association between vessel-specific coronary Aggregated plaque burden, Agatston score and hemodynamic significance of coronary disease (The CAPTivAte study).

Background: CT coronary angiography (CTCA) is a guideline-endorsed assessment for patients with stable angina and suspected coronary disease. Although associated with excellent negative predictive value in ruling out obstructive coronary disease, there are limitations in the ability of CTCA to predict hemodynamically significant coronary disease. The CAPTivAte study aims to assess the utility of Aggregated Plaque Burden (APB) in predicting ischemia based on Fractional Flow Reserve (FFR). Methods: In this retrospective study, patients who had a CTCA and invasive FFR of the LAD were included. The entire length of the LAD was analyzed using semi-automated software which characterized total plaque burden and plaque morphological subtype (including Low Attenuation Plaque (LAP), Non-calcific plaque (NCP) and Calcific Plaque (CP). Aggregated Plaque Burden (APB) was calculated. Univariate and multivariate analysis were performed to assess the association between these CT-derived parameters and invasive FFR. Results: There were 145 patients included in this study. 84.8 % of patients were referred with stable angina. There was a significant linear association between APB and FFR in both univariate and multivariate analysis (Adjusted R-squared = 0.0469; p = 0.035). Mean Agatston scores are higher in FFR positive vessels compared to FFR negative vessels (371.6 (±443.8) vs 251.9 (±283.5, p = 0.0493). Conclusion: CTCA-derived APB is a reliable predictor of ischemia assessed using invasive FFR and may aid clinicians in rationalizing invasive vs non-invasive management strategies. Vessel-specific Agatston scores are significantly higher in FFR-positive vessels than in FFR-negative vessels. Associations between HU-derived plaque subtype and invasive FFR were inconclusive in this study.