Perivascular Fat Research Articles

Evaluation of Pericoronary Fat Attenuation Index to Better Identify Culprit Lesions in Acute Coronary Syndrome According to Stenosis Severity.

To investigate the incremental value of pericoronary fat attenuation index (FAI) in routine coronary artery computed tomography angiography (CCTA) to identify culprit lesions in acute coronary syndrome (ACS). We reviewed the CCTA data from 80 ACS patients and 40 individuals with stable coronary atherosclerosis. ACS patient plaques were categorized into culprit and nonculprit groups. The plaque-specific pericoronary FAI was assessed using the Perivascular Fat Analysis Tool. We applied a default prespecified window of -190 to -30 Hounsfield units (HU) and a broader prespecified window of -190 to 20 HU. FAI values within these prespecified windows and the types and severity of plaque stenosis were compared across the 3 groups. Additionally, we investigated high-risk characteristics of plaques in the ACS group and their correlation with FAI. The effectiveness and worthiness of FAI in identifying culprit lesions were analyzed based on the receiver operating characteristic curve. The FAI values under the 2 prespecified windows were higher in the culprit group than in the nonculprit and control groups (all P < 0.001). The culprit group showed the most mixed plaques and the most severe stenosis (all P < 0.001). In the ACS group, the FAI value was significantly lower around calcified lesions (-85.00 ± 9.97 HU) than around noncalcified (-78.00 ± 11.52 HU) and mixed plaques (-78.00 ± 9.24 HU) (both P < 0.001). The culprit group had more high-risk plaques, and high-risk plaques had higher FAI values than those without high-risk characteristics (-70.00 ± 7.67 HU vs -82.00 ± 10.16 HU, P < 0.001). The efficacy of FAI under the default prespecified window in identifying culprit lesions was higher compared than that under the broader prespecified window (area under the curve = 0.799 vs 0.761, P = 0.042), and the diagnostic cutoff values were -77 versus -58 HU. The FAI under the default prespecified window exhibited an incremental value for identifying culprit lesions, as compared with stenosis severity (area under the curve = 0.970 vs 0.939, P < 0.001). The culprit lesions have higher FAI than the nonculprit lesions and the controls. FAI is a worthy parameter for identifying culprit lesions in routine CCTA according to stenosis severity, and the default prespecified window is a better option.

Comparative Prognostic Value of Coronary Calcium Score and Perivascular Fat Attenuation Index in Coronary Artery Disease.

Coronary artery disease (CAD) is the leading global cause of mortality, accounting for approximately 30% of all deaths. It is primarily characterized by the accumulation of atherosclerotic plaques within the coronary arteries, leading to reduced blood flow to the heart muscle. Early detection of atherosclerotic plaques is crucial to prevent major adverse cardiac events. Notably, recent studies have shown that 15% of myocardial infarctions occur in patients with non-obstructive CAD, underscoring the importance of comprehensive plaque assessment beyond merely identifying obstructive lesions. Cardiac Computed Tomography Angiography (CCTA) has emerged as a cost-effective and efficient technique for excluding obstructive CAD, particularly in patients with a low-to-intermediate clinical likelihood of the disease. Recent advancements in CCTA technology, such as improved resolution and reduced scan times, have mitigated many technical challenges, allowing for precise quantification and characterization of both calcified and non-calcified atherosclerotic plaques. This review focuses on two critical physiological aspects of atherosclerotic plaques: the burden of calcifications, assessed via the coronary artery calcium score (CACs), and perivascular fat attenuation index (pFAI), an emerging marker of vascular inflammation. The CACs, obtained through non-contrast CT scans, quantifies calcified plaque burden and is widely used to stratify cardiovascular risk, particularly in asymptomatic patients. Despite its prognostic value, the CACs does not provide information on non-calcified plaques or inflammatory status. In contrast, the pFAI, derived from CCTA, serves as an indirect marker of coronary inflammation and has shown potential in predicting adverse cardiac events. Combining both CACs and pFAI assessment could offer a comprehensive risk stratification approach, integrating the established calcification burden with novel inflammatory markers to enhance CAD prevention and management strategies.

Correlation analysis of carotid adipose tissue density and plaque stability in patients with carotid artery stenosis

Objective: To investigate the correlation between perivascular fat density (PFD) and plaque stability in patients with carotid artery stenosis. Methods: Clinical data of 110 patients with carotid artery stenosis treated at Drum Tower Hospital, Nanjing University Medical School from January 2018 to December 2022 were retrospectively collected. Based on pathological results of carotid plaque specimens obtained from carotid endarterectomy (CEA), patients were categorized into stable plaque group (n=51) and vulnerable plaque group (n=59). All patients underwent preoperative carotid CT angiography (CTA) to measure PFD at the narrowest carotid artery. Preoperative levels of interleukin-6 (IL-6) and other hematological parameters were collected. Multivariable logistic regression analysis was used to identify factors associated with plaque stability in carotid artery stenosis patients. Area under the curve (AUC) of receiver operating characteristic (ROC) was performed to evaluate the predictive value of PFD for plaque stability. Results: The stable plaque group consisted of 43 males and 8 females with a mean age of (67.6±9.0) years, while the vulnerable plaque group comprised 48 males and 11 females with a mean age of (69.3±9.0) years. The proportions of smokers were 31.4% (16/51) and 50.8% (30/59) in the stable and vulnerable plaque groups, respectively. The proportions of patients with diabetes were 33.3% (17/51) and 52.5% (31/59), respectively. IL-6 levels were 3.46(2.67, 5.34) and 4.51(3.62, 5.51) ng/L in the stable and vulnerable groups, respectively. Mean PFD values were (-69.04±5.35) and (-63.24±6.08) HU, respectively, with maximum PFD values of (-62.90±6.98) and (-56.93±5.90) HU, respectively. The differences were statistically significant (all P<0.05). Multivariable logistic regression analysis showed that increased mean PFD (OR=1.167, 95%CI: 1.029-1.324, P=0.016) and elevated IL-6 levels (OR=1.489, 95%CI: 1.151-1.926, P=0.002) were associated with vulnerability of carotid artery plaques. ROC curve analysis results showed that a cut-off value of -65.5 HU, the AUC for predicting plaque stability based on the mean PFD was 0.756 (95%CI: 0.667-0.844, P<0.001), with sensitivity of 64.4% and specificity of 74.5%. Conclusion: Increased mean PFD at the narrowest carotid artery is associated with vulnerability of plaques in patients with carotid artery stenosis.

Perivascular Fat: A Novel Risk Factor for Coronary Artery Disease.

Perivascular adipose tissue (PVAT) interacts with the vascular wall and secretes bioactive factors which regulate vascular wall physiology. Vice versa, vascular wall inflammation affects the adjacent PVAT via paracrine signals, which induce cachexia-type morphological changes in perivascular fat. These changes can be quantified in pericoronary adipose tissue (PCAT), as an increase in PCAT attenuation in coronary computed tomography angiography images. Fat attenuation index (FAI), a novel imaging biomarker, measures PCAT attenuation around coronary artery segments and is associated with coronary artery disease presence, progression, and plaque instability. Beyond its diagnostic capacity, PCAT attenuation can also ameliorate cardiac risk stratification, thus representing an innovative prognostic biomarker of cardiovascular disease (CVD). However, technical, biological, and anatomical factors are weakly related to PCAT attenuation and cause variation in its measurement. Thus, to integrate FAI, a research tool, into clinical practice, a medical device has been designed to provide FAI values standardized for these factors. In this review, we discuss the interplay of PVAT with the vascular wall, the diagnostic and prognostic value of PCAT attenuation, and its integration as a CVD risk marker in clinical practice.

Pericarotid Fat as a Marker of Cerebrovascular Risk.

Vascular inflammation is widely recognized as an important factor in the atherosclerotic process, particularly in terms of plaque development and progression. Conventional tests, such as measuring circulating inflammatory biomarkers, lack the precision to identify specific areas of vascular inflammation. In this context, noninvasive imaging modalities can detect perivascular fat changes, serving as a marker of vascular inflammation. This review aims to provide a comprehensive overview of the key concepts related to perivascular carotid fat and its pathophysiology. Additionally, we examine the existing literature on the association of pericarotid fat with features of plaque vulnerability and cerebrovascular events. Finally, we scrutinize the advantages and limitations of the noninvasive assessment of pericarotid fat.

Assessment of aortic perivascular and renal sinus fat in endogenous cortisol excess of different etiology.

Endogenous cortisol excess is known to affect body fat distribution. Ectopic fat is the accumulation of triglycerides in non-adipose tissue regions that normally contain little fat. The aim of study was to investigate the amount of ectopic fat in aortic perivascular and renal sinus fat of patients with endogenous cortisol excess and its relationship with their comorbitidies and laboratory findings. A total of 119 patients, including 16 patients with pituitary Cushing's disease (CD), 21 patients with adrenal Cushing's syndrome (CS), 34 patients with mild autonomous cortisol secretion (MACS), and 48 patients with nonfunctioning adrenal adenomas were enrolled in this retrospective study. Aortic perivascular fat and renal sinus fat were evaluated with magnetic resonance imaging. It was determined that the amount of aortic perivascular fat was increased in patients with CD (P = 0.01). The linear regression analysis showed that the amount of perivascular fat was associated with triglyceride levels and cortisol levels after the 1mg dexamethasone suppression test as well as with gender (P < 0.01). Renal sinus fat measurements were similar in the groups (P > 0.05). After adjusting for age, sex, and BMI, perivascular fat was found to be higher in pituitary the CD than in the MACS and the nonfunctioning adenoma groups, and renal sinus fat was seen to be higher in pituitary the CD than in the MACS groups (P < 0.05). Patients with diabetes mellitus had an increased amount of renal sinus fat (P = 0.008). The amount of perivascular and renal sinus fat may increase in patients with CD. Further studies are needed to elucidate ectopic fat distribution in patients with endogenous cortisol excess.

Morphometry of left atrial appendage isthmus and mitral isthmus: implications for atrial fibrillation catheter ablation.

Radiofrequency catheter ablation (RFA) targets the left atrial appendage isthmus (LAA isthmus) and mitral isthmus for treatment of atrial fibrillation. However, proximity of left circumflex artery (LCxA) and great cardiac vein (GCV) in the isthmuses poses fatal risks during ablation. This study investigated relationships of LCxA and GCV across three lines in the LAA and mitral isthmus, using 15 human cadaveric hearts. Distances between the vessels and the endocardium, myocardium, and perivascular fat thickness were measured. The results showed that LCxA was mostly consistently located in lower atrial segments and GCV was in lower/upper atrial segments, with change of course mainly observed in the middle of the LAA. The LCxA was found as close as 3-5 mm from the lower border of the LAA isthmus in 80% of specimens, at a depth of 2-3 mm within the LAA isthmus, where 1 mm consisted of myocardium and the remainder was fat, which may not provide adequate protection due to the possibility of liquefaction of fat with heat application. The effective myocardial thickness was consistently 1 mm across all cases in both isthmuses. LCxA was 2 mm in second and third sections of LAA isthmus ("careful segment"). LCxA distances from left inferior pulmonary vein opening was 5 to 12 mm, occasionally dangerously close as <1 mm in 16% of cases. This study measured LCxA and GCV in the LAA and mitral isthmus across three lines for the first time in the Indian population, aiding surgeons in RFA planning.

Ultrasound-guided perineural injection of the saphenous nerve in goat cadavers

BackgroundSurgery of the goat stifle joint requires good perioperative analgesia, ideally without affecting motor function in the postoperative period. The objective of this study was to describe an ultrasound-guided technique for saphenous nerve block in goats. Eleven fresh female goat cadavers from two different age groups were used: seven of them were four years old with a mean ± SD body weight of 65.9 ± 7.3 kg. Four animals were six months old and their mean ± SD body weight was 20.1 ± 3.1 kg. The cadavers were positioned in lateral recumbency with the limb to be blocked lowermost. A high-frequency linear transducer (6–12 MHz) was used to localise the interfascial plane between the sartorius and the vastus medialis muscles and to identify the saphenous nerve on the medial aspect of the thigh, caudal to the femur, at the level of the femoral triangle. In 22 pelvic limbs 0.1 mL/kg of methylene blue was injected around the saphenous nerve under ultrasound guidance, followed by gross anatomical dissection. The length of circumferentially stained nerve was measured, and the success rate of achieving at least 1 cm of staining is presented with a 95% confidence interval (CI).ResultsAlthough not all saphenous nerves were sonographically identified, their boundaries were defined as cranial to the femoral artery, lateral to the sartorius muscle, and medial to the vastus medialis and rectus femoris muscles, within the perivascular fat. During anatomical dissection, the overall dye solution distribution was graded as complete in 17/22 limbs indicating a 77.3% success rate [95% CI (0.598, 0.948)], partial in 3/22 limbs and failed in 2/22 limbs.ConclusionsThe success rate of this study indicates the feasibility of employing the ultrasound-guided technique to perform saphenous nerve block in goats. However, further in-vivo studies are recommended to assess the block's clinical efficacy before implementation on clinical patients.

Statin Therapy Mitigates Oxidative Stress in Epicardial and Perivascular Adipose Tissue: A Pilot Study in Cardiac Surgery Patients

Epicardial and perivascular adipose tissues have gained significant attention in the past decade due to their involvement in complex metabolic shifts and inflammatory changes in cardiovascular diseases. Statins, the cornerstone of lipid-lowering therapy, have pleiotropic effects, including the potential of alleviating epicardial adipose dysfunction and inflammation, although their impact on local oxidative stress has received less scrutiny. This study was purported to assess the production of reactive oxygen species (ROS) in epicardial and perivascular fat samples harvested from patients undergoing elective cardiac surgery and who were treated or not with statins. Here, we report that patients chronically treated with statins (atorvastatin and rosuvastatin) exhibited significantly lower levels of ROS in their epicardial and perivascular adipose tissues. Additionally, a positive correlation was observed between adipose tissue oxidative stress and the diameter of the right ventricle. Larger studies are required to provide mechanistic insights regarding the sources of epicardial ROS and signal transduction pathways activated by statins.

Quantification of subclinical plaque characteristics and perivascular fat using coronary computed tomography angiography (CCTA) among individuals with human immunodeficiency virus (HIV).

People infected with human immunodeficiency virus (PIWH) have a higher risk of cardiovascular events. This study was designed to compare the differences in plaque characteristics and perivascular fat between subclinical coronary atherosclerosis in PIWH and healthy controls (HC) by coronary computed tomography angiography (CCTA). We also assessed the associations between human immunodeficiency virus (HIV) infection, antiretroviral therapy (ART), and coronary artery disease (CAD). This cross-sectional study included a total of 158 PIWH and 79 controls. CCTA was used to evaluate coronary artery plaque prevalence, coronary stenosis severity, plaque composition, plaque volume, and perivascular fat attenuation index (FAI). Logistic regression analyses were used to assess the associations between the prevalence of coronary artery plaque and HIV-related clinical indicators. There was no difference in total coronary artery plaque prevalence between PIWH and controls (44.3% vs. 32.9%; P=0.09), but the prevalence of noncalcified plaque was significantly higher in PIWH compared with the controls (33.5% vs. 16.5%; P=0.006). After adjustment for age, sex, statin use, and family history of cardiovascular disease (CVD), the prevalence of noncalcified plaque remained 2 times higher in PIWH [odds ratio (OR), 2.082; 95% confidence interval (CI): 1.007-4.304; P=0.048]. The perivascular FAI measured around the left anterior descending artery (LAD) was higher in PIWH (-71.4±5.7 vs. -73.5±7.0; P=0.03) compared with that of the controls. The intra-group analyses of PIWH suggested that the decrease in nadir CD4+ T-cell count was associated with the increased prevalence of noncalcified plaque (OR, 4.139; 95% CI: 1.312-13.060; P=0.02). PIWH have a higher risk of developing noncalcified plaque and greater perivascular fat. In addition, the increased noncalcified plaque prevalence in PIWH may be associated with the immunodeficiency caused by HIV.

A cloud-based medical device for predicting cardiac risk in suspected coronary artery disease: a rapid review and conceptual economic model.

The CaRi-Heart® device estimates risk of 8-year cardiac death, using a prognostic model, which includes perivascular fat attenuation index, atherosclerotic plaque burden and clinical risk factors. To provide an Early Value Assessment of the potential of CaRi-Heart Risk to be an effective and cost-effective adjunctive investigation for assessment of cardiac risk, in people with stable chest pain/suspected coronary artery disease, undergoing computed tomography coronary angiography. This assessment includes conceptual modelling which explores the structure and evidence about parameters required for model development, but not development of a full executable cost-effectiveness model. Twenty-four databases, including MEDLINE, MEDLINE In-Process and EMBASE, were searched from inception to October 2022. Review methods followed published guidelines. Study quality was assessed using Prediction model Risk Of Bias ASsessment Tool. Results were summarised by research question: prognostic performance; prevalence of risk categories; clinical effects; costs of CaRi-Heart. Exploratory searches were conducted to inform conceptual cost-effectiveness modelling. The only included study indicated that CaRi-Heart Risk may be predictive of 8 years cardiac death. The hazard ratio, per unit increase in CaRi-Heart Risk, adjusted for smoking, hypercholesterolaemia, hypertension, diabetes mellitus, Duke index, presence of high-risk plaque features and epicardial adipose tissue volume, was 1.04 (95% confidence interval 1.03 to 1.06) in the model validation cohort. Based on Prediction model Risk Of Bias ASsessment Tool, this study was rated as having high risk of bias and high concerns regarding its applicability to the decision problem specified for this Early Value Assessment. We did not identify any studies that reported information about the clinical effects or costs of using CaRi-Heart to assess cardiac risk. Exploratory searches, conducted to inform the conceptual cost-effectiveness modelling, indicated that there is a deficiency with respect to evidence about the effects of changing existing treatments or introducing new treatments, based on assessment of cardiac risk (by any method), or on measures of vascular inflammation (e.g. fat attenuation index). A de novo conceptual decision-analytic model that could be used to inform an early assessment of the cost effectiveness of CaRi-Heart is described. A combination of a short-term diagnostic model component and a long-term model component that evaluates the downstream consequences is anticipated to capture the diagnosis and the progression of coronary artery disease. The rapid review methods and pragmatic additional searches used to inform this Early Value Assessment mean that, although areas of potential uncertainty have been described, we cannot definitively state where there are evidence gaps. The evidence about the clinical utility of CaRi-Heart Risk is underdeveloped and has considerable limitations, both in terms of risk of bias and applicability to United Kingdom clinical practice. There is some evidence that CaRi-Heart Risk may be predictive of 8-year risk of cardiac death, for patients undergoing computed tomography coronary angiography for suspected coronary artery disease. However, whether and to what extent CaRi-Heart represents an improvement relative to current standard of care remains uncertain. The evaluation of the CaRi-Heart device is ongoing and currently available data are insufficient to fully inform the cost-effectiveness modelling. A large (n=15,000) ongoing study, NCT05169333, the Oxford risk factors and non-invasive imaging study, with an estimated completion date of February 2030, may address some of the uncertainties identified in this Early Value Assessment. This study is registered as PROSPERO CRD42022366496. This award was funded by the National Institute for Health and Care Research (NIHR) Evidence Synthesis programme (NIHR award ref: NIHR135672) and is published in full in Health Technology Assessment; Vol. 28, No. 31. See the NIHR Funding and Awards website for further award information.

Perivascular fat attenuation index value and plaque volume increased in non-target lesions of coronary arteries after stenting.

Progression of non-target lesions (NTLs) after stenting has been reported and is associated with the triggering of an inflammatory response. The perivascular fat attenuation index (FAI) may be used as a novel imaging biomarker for the direct quantification of coronary inflammation. To investigate whether FAI values can help identify changes in inflammation status in patients undergoing stent implantation, especially in NTLs. Patients who underwent pre- and post-stenting coronary computed tomography angiography (CCTA) examination between January 2015 and February 2021 were consecutively enrolled. The pre- and post-stenting FAIs of the full coronary arteries were compared in both the non- and stent-implanted coronary arteries. Moreover, local FAI values were measured and compared between the NTLs and target lesions in the stent implantations. We also compared changes in plaque type and volume in NTLs before and after stenting. A total of 89 patients (mean age 61 years; male 59) were enrolled. The perivascular FAI values in the full coronary arteries decreased after stenting in both the non- and stent-implanted coronary arteries, similar to those in the target lesions. Conversely, the perivascular FAI values in the NTLs increased after stenting (p < 0.05). In addition, the plaque volumes significantly increased in the NTLs after stenting, regardless of whether they were non-calcified, mixed, or calcified (p < 0.05). Perivascular FAI values and plaque volumes increased in the NTLs after stenting. Perivascular FAI can be a promising imaging biomarker for monitoring coronary inflammation after stenting and facilitate long-term monitoring in clinical settings. Perivascular fat attenuation index, a non-invasive imaging biomarker, may help identify coronary arteries with high inflammation in non-target lesions and facilitate long-term monitoring, potentially providing an opportunity for more targeted treatment. • Perivascular fat attenuation index (FAI) values and plaque volumes increased in the non-target lesions (NTLs) after stenting, suggesting potential focal inflammation progression after stenting. However, stenting along with anti-inflammatory treatment ameliorated inflammation in the full coronary arteries. • Perivascular FAI, a non-invasive imaging biomarker, may help identify coronary arteries with high inflammation in NTLs and facilitate long-term monitoring, potentially providing an opportunity for more targeted treatment.

Analysis of the perivascular fat attenuation index and quantitative plaque parameters in relation to haemodynamically impaired myocardial ischaemia.

To investigate the correlation between quantitative plaque parameters, the perivascular fat attenuation index, and myocardial ischaemia caused by haemodynamic impairment. Patients with stable angina who had invasive flow reserve fraction (FFR) assessment and coronary artery computed tomography (CT) angiography were retrospectively enrolled. A total of 138 patients were included in this study, which were categorized into the FFR < 0.75 group (n = 43), 0.75 ≤ FFR ≤ 0.8 group (n = 37), and FFR > 0.8 group (n = 58), depending on the range of FFR values. The perivascular FAI and CTA-derived parameters, including plaque length (PL), total plaque volume (TPV), minimum lumen area (MLA), and narrowest degree (ND), were recorded for the lesions. An FFR < 0.75 was defined as myocardial-specific ischaemia. The relationships between myocardial ischaemia and parameters such as the PL, TPV, MLA, ND, and FAI were analysed using a logistic regression model and receiver operating characteristic (ROC) curves to compare the diagnostic accuracy of various indicators for myocardial ischaemia. The PL, TPV, ND, and FAI were greater in the FFR < 0.75 group than in the grey area group and the FFR > 0.80 group (all p < 0.05). The MLA in the FFR < 0.75 group was lower than that in the grey area group and the FFR > 0.80 group (both P < 0.05). There were no significant differences in the PL, TPV, or ND between the grey area and the FFR > 0.80 group, but there was a significant difference in the FAI. The coronary artery lesions with FFRs ≤ 0.75 had the greatest FAI values. Multivariate analysis revealed that the perivascular FAI and PL density are significant predictors of myocardial ischaemia. The FAI has some predictive value for myocardial ischaemia (AUC = 0.781). After building a combination model using the FAI and plaque length, the predictive power increased (AUC, 0.781 vs. 0.918), and the change was statistically significant (P < 0.001). The combined model of PL + FAI demonstrated great diagnostic efficacy in identifying myocardial ischaemia caused by haemodynamic impairment; the lower the FFR was, the greater the FAI. Thus, the PL + FAI could be a combined measure to securely rule out myocardial ischaemia.

Lp(a) and vascular inflammation: data from perivascular fat attenuation index measurements

Lp(a) and vascular inflammation: data from perivascular fat attenuation index measurements

Inflammatory risk and cardiovascular events in patients without obstructive coronary artery disease: the ORFAN multicentre, longitudinal cohort study

Coronary computed tomography angiography (CCTA) is the first line investigation for chest pain, and it is used to guide revascularisation. However, the widespread adoption of CCTA has revealed a large group of individuals without obstructive coronary artery disease (CAD), with unclear prognosis and management. Measurement of coronary inflammation from CCTA using the perivascular fat attenuation index (FAI) Score could enable cardiovascular risk prediction and guide the management of individuals without obstructive CAD. The Oxford Risk Factors And Non-invasive imaging (ORFAN) study aimed to evaluate the risk profile and event rates among patients undergoing CCTA as part of routine clinical care in the UK National Health Service (NHS); to test the hypothesis that coronary arterial inflammation drives cardiac mortality or major adverse cardiac events (MACE) in patients with or without CAD; and to externally validate the performance of the previously trained artificial intelligence (AI)-Risk prognostic algorithm and the related AI-Risk classification system in a UK population. This multicentre, longitudinal cohort study included 40 091 consecutive patients undergoing clinically indicated CCTA in eight UK hospitals, who were followed up for MACE (ie, myocardial infarction, new onset heart failure, or cardiac death) for a median of 2·7 years (IQR 1·4-5·3). The prognostic value of FAI Score in the presence and absence of obstructive CAD was evaluated in 3393 consecutive patients from the two hospitals with the longest follow-up (7·7 years [6·4-9·1]). An AI-enhanced cardiac risk prediction algorithm, which integrates FAI Score, coronary plaque metrics, and clinical risk factors, was then evaluated in this population. In the 2·7 year median follow-up period, patients without obstructive CAD (32 533 [81·1%] of 40 091) accounted for 2857 (66·3%) of the 4307 total MACE and 1118 (63·7%) of the 1754 total cardiac deaths in the whole of Cohort A. Increased FAI Score in all the three coronary arteries had an additive impact on the risk for cardiac mortality (hazard ratio [HR] 29·8 [95% CI 13·9-63·9], p<0·001) or MACE (12·6 [8·5-18·6], p<0·001) comparing three vessels with an FAI Score in the top versus bottom quartile for each artery. FAI Score in any coronary artery predicted cardiac mortality and MACE independently from cardiovascular risk factors and the presence or extent of CAD. The AI-Risk classification was positively associated with cardiac mortality (6·75 [5·17-8·82], p<0·001, for very high risk vs low or medium risk) and MACE (4·68 [3·93-5·57], p<0·001 for very high risk vs low or medium risk). Finally, the AI-Risk model was well calibrated against true events. The FAI Score captures inflammatory risk beyond the current clinical risk stratification and CCTA interpretation, particularly among patients without obstructive CAD. The AI-Risk integrates this information in a prognostic algorithm, which could be used as an alternative to traditional risk factor-based risk calculators. British Heart Foundation, NHS-AI award, Innovate UK, National Institute for Health and Care Research, and the Oxford Biomedical Research Centre.

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

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). 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. 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 (β [95% CI], 29.233 [10.436, 48.03], P = 0.014), CS duration (β [95% CI], 0.176 [0.185, 4.242], P = 0.033), and UFC (β [95% CI], 0.197 [1.803, 19.719], P = 0.019) were strongly associated with EAT volume but not EAT density, and EAT volume (β [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. 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.

Relationships between the coronary fat attenuation index for patients with heart-related disease measured automatically on coronary computed tomography angiography and coronary adverse events and degree of coronary stenosis.

Pericoronary artery coronary tissue (PACT) is a type of epicardial fat that can reflect the state of the coronary artery (inflammation, etc.). However, it cannot be reasonably and efficiently utilized in routine computed tomography (CT) examination. The aim of this study was to use artificial intelligence (AI) software to analyze coronary computed tomography angiography (CCTA) and measure the coronary perivascular fat attenuation index (FAI) of patients. The relationship between FAI and the occurrence of coronary adverse events and the degree of coronary stenosis were further analyzed. This study involved patients who experienced CCTA in West China Hospital, Sichuan University, from January 2012 to December 2012. These patients were followed up to 2020 and classified according to the occurrence of coronary adverse events and the degree of stenosis of the lumen. For all patients, AI software was used to analyze the CCTA images of patients, and the FAI of 3 coronary arteries, the left anterior descending artery (LAD), the left circumflex artery (LCX), and the right coronary artery (RCA), was measured. Moreover, the relationship between FAI and patients with different degrees of coronary stenosis and adverse coronary events was determined. Comparisons between any 2 groups showed that the differences in the FAI among the 4 groups for the LAD were significant (all P values <0.05). There were no significant differences between the group with less-than-moderate stenosis (Mb) without adverse events and the group with moderate-or-above stenosis (M) with no adverse events for the LCX (P>0.05). For the remaining groups, FAI values exhibited statistically significant differences (P<0.05). According to the degree of lumen stenosis, the patients were divided into groups according to LAD, LCX, and RCA and the sum of the 3 vessels. There were significant differences in coronary FAI among the groups with different degrees of lumen stenosis for the sum of the 3 vessels, the LAD, and the LCX (P<0.05). FAI can reflect the state of the coronary artery, which is related to inflammation of the coronary lumen. Moreover, there is a relationship between FAI and the degree of stenosis in the coronary lumen: the narrower the coronary lumen is, the higher the FAI around the lumen.

Mechanisms and treatment of obesity-related hypertension-Part 1: Mechanisms.

The prevalence of obesity has tripled over the past five decades. Obesity, especially visceral obesity, is closely related to hypertension, increasing the risk of primary (essential) hypertension by 65%-75%. Hypertension is a major risk factor for cardiovascular disease, the leading cause of death worldwide, and its prevalence is rapidly increasing following the pandemic rise in obesity. Although the causal relationship between obesity and high blood pressure (BP) is well established, the detailed mechanisms for such association are still under research. For more than 30 years sympathetic nervous system (SNS) and kidney sodium reabsorption activation, secondary to insulin resistance and compensatory hyperinsulinemia, have been considered as primary mediators of elevated BP in obesity. However, experimental and clinical data show that severe insulin resistance and hyperinsulinemia can occur in the absence of elevated BP, challenging the causal relationship between insulin resistance and hyperinsulinemia as the key factor linking obesity to hypertension. The purpose of Part 1 of this review is to summarize the available data on recently emerging mechanisms believed to contribute to obesity-related hypertension through increased sodium reabsorption and volume expansion, such as: physical compression of the kidney by perirenal/intrarenal fat and overactivation of the systemic/renal SNS and the renin-angiotensin-aldosterone system. The role of hyperleptinemia, impaired chemoreceptor and baroreceptor reflexes, and increased perivascular fat is also discussed. Specifically targeting these mechanisms may pave the way for a new therapeutic intervention in the treatment of obesity-related hypertension in the context of 'precision medicine' principles, which will be discussed in Part 2.

Prognostic value of preprocedural pericoronary adipose tissue CT-Attenuation in patients with non ST-elevation acute coronary syndrome

Abstract Background Pericoronary adipose tissue attenuation expressed by fat attenuation index (FAI) on coronary CT angiography (CCTA) reflects pericoronary inflammation. FAI has been reported to be associated with cardiac mortality in patients with suspected coronary artery disease. However, the prognostic value of FAI in patients with non ST-elevation acute coronary syndrome (NSTE-ACS) after percutaneous coronary intervention (PCI) remains elusive. Methods This retrospective single-center observational study included a total of 358 patients with NSTE-ACS who underwent preprocedural 320-slice CCTA and emergent PCI within 24 hours from admission. Perivascular fat attenuation mapping was done around the three major coronary arteries-the proximal (4cm) right coronary artery (RCA), the left anterior descending artery (LAD), and the left circumflex artery (LCx). We assessed the prognostic value of FAI for all-cause and cardiac mortality. Clinical outcomes were assessed by death and cardiac death. Results During a median follow-up period of 1715 days (1008-2538), death and cardiac death occurred in 36 (10.1%) patients and 18 (5.0%) patients, respectively. High FAI values around LAD and LCx (but not around RCA) were predictive of all-cause mortality. High FAI values around RCA, LAD, and LCx were predictive of cardiac mortality. FAI in culprit vessels and average FAI values in three vessels were predictive of all-cause and cardiac mortality. ROC analysis revealed that the best cut-off FAI value in three vessels for predicting cardiac death is -65.8 (AUC: 0.752, 0.637-0.867.) Kaplan-Meier analysis revealed that patients with average FAI values in three vessels &amp;gt;-65.8 were significantly associated with poor prognosis of cardiac mortality. (P&amp;lt;0.001). Conclusion High perivascular FAI values are an indicator of increased cardiac mortality and, therefore, could guide early targeted secondary prevention and intensive medical management in patients with NSTE-ACS after PCI.Kaplan Meier analysis for cardiac death

Genetic variability of lipoprotein(a) controls vascular inflammation/redox signalling and predicts adverse cardiovascular outcomes in coronary artery disease

Abstract Introduction Lipoprotein(a) [Lp(a)] has an established link with cardiovascular disease, however the underlying mechanisms are incompletely understood. Objective We investigate the prognostic value of LPA genetic variants that determine Lp(a) levels, in patients with coronary artery disease. Methods We determined the plasma Lp(a) levels of 1472 cardiac surgery patients and performed genotyping to identify 7 SNPs in LPA that are associated with increased Lp(a) levels. We compared subjects with alternative LPA alleles from ≥3 SNPs (alternative group) to those without (reference group). The arterial redox state of internal mammary artery (IMA) samples was quantified using lucigenin chemiluminescence and nicotinamide adenine dinucleotide phosphate (NADPH). Coronary inflammation was measured using coronary CT angiography (CCTA) by applying Perivascular Fat Attenuation Indexing (FAI) in the proximal left anterior descending (LAD) coronary artery. To best describe cytokine-driven vascular inflammation, a radiotranscriptomic signature (C19RS) derived from the perivascular space around the aorta and the IMA was used. Patients were followed up for a median of 7.8 years. Results Patients with high plasma Lp(a) levels, those in the top third of the population, had significantly increased arterial NADPH-stimulated O2.- (A) compared to those with medium or low plasma Lp(a) levels. Amongst patients with high plasma Lp(a): those with Lp(a) levels ≥75th percentile (compared to those below) had a significantly increased perivascular FAI (B), and those with Lp(a) levels ≥95th percentile (compared to those below) had a significantly increased C19RS (C). Images of CCTA FAI mapping of LADs from alternative and reference LPA variant group patients are shown (D). Amongst insulin-sensitive patients with high plasma Lp(a), those in the alternative LPA variant group (vs the reference group) had significantly increased plasma Lp(a) levels (p&amp;lt;0.001), plasma apolipoprotein-B (ApoB) levels (p=0.025), resting arterial O2.- levels (E), and C19RS (F). There was a significantly increased observed risk of major adverse cardiovascular events, independent of plasma ApoB, for patients with high plasma Lp(a) levels (adj. HR=2.664, p=0.022) as well as for those in the alternative LPA variant group (adj. HR=2.018, p=0.049). IMA RNAseq pathway enrichment analyses revealed that, in patients with plasma Lp(a) levels ≥95th percentile, there was a significant upregulation of genes involved in the mitochondrial electron transport chain, reactive oxygen species response and positive regulation of lymphocyte chemotaxis. Conclusions We demonstrate for the first time that Lp(a) leads to increased coronary inflammation in humans, which could mediate the increased risk of major adverse cardiovascular events associated with high Lp(a) levels.