High-risk Coronary Plaque Research Articles

Relationship between Epicardial Adipose Tissue and High-Risk Coronary Plaque Features in Patients with Suspected Acute Coronary Syndrome

Objective: To evaluate the association between EAT volume and attenuation and high-risk coronary plaque (HRP) in patients with suspected acute coronary syndrome (ACS). Material and Methods: In this prospective study were enrolled, from November 2020 to August 2021, consecutive patients who underwent cardiac computed tomography (CCT) for suspected ACS. All exams were performed using a 2x192-slice dual source CT scanner. EAT volume and attenuation were evaluated in all patients. HRP was defined as plaque with more than 2 high-risk features (low attenuation plaque, positive remolding, napkin-ring sign, spotty calcification) on CCT image. Based on the presence or absence of HRP patients were divided into two groups and EAT volume and attenuation were compared. Results: In this study were enrolled 106 patients: 37 with HRP and 69 without HRP. Patients with HRP have higher EAT volume and attenuation than those without HRP, respectively, 119.0±14.0 cm3 vs 96.3±8.3 cm3 (p<0.0001) and -85.7±15.7 HU vs -95.0±18.4 HU (p=0.0108). After adjustment by coronary calcium score (CCS) and coronary stenosis, EAT volume and attenuation were independent risk predictors of presence of HRP. Conclusions: Higher EAT volume and attenuation are associated with HRP in patient with ACS and are independent of CCS and coronary stenosis.

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

BackgroundHigh-risk coronary artery plaque (HRP) is associated with increased risk of acute coronary syndrome.We aimed to investigate the prevalence of HRP in asymptomatic patients with type 2 diabetes (T2D), and its relation to patient characteristics including cardiovascular risk factors, diabetes profile, and coronary artery calcium score (CACS).MethodsAsymptomatic patients with T2D and no previous coronary artery disease (CAD) were studied using coronary computed tomography angiography (CCTA) in this descriptive study. Plaques with two or more high-risk features (HRP) defined by low attenuation, positive remodeling, spotty calcification, and napkin-ring sign were considered HRP. In addition, total atheroma volume (TAV), proportions of dense calcium, fibrous, fibrous-fatty and necrotic core volumes were assessed. The CACS was obtained from non-enhanced images by the Agatston method. Cardiovascular and diabetic profiles were assessed in all patients.ResultsIn 230 patients CCTA was diagnostic and 161 HRP were detected in 86 patients (37%). Male gender (OR 4.19, 95% CI 1.99–8.87; p < 0.01), tobacco exposure in pack years (OR 1.02, 95% CI 1.00–1.03; p = 0.03), and glycated hemoglobin (HbA1c) (OR 1.04, 95% CI 1.02–1.07; p < 0.01) were independent predictors of HRP. No relationship was found to other risk factors. HRP was not associated with increased CACS, and 13 (23%) patients with zero CACS had at least one HRP.ConclusionA high prevalence of HRP was detected in this population of asymptomatic T2D. The presence of HRP was associated with a particular patient profile, but was not ruled out by the absence of coronary artery calcium. CCTA provides important information on plaque morphology, which may be used to risk stratify this high-risk population.Trial registration This trial was retrospectively registered at clinical trials.gov January 11, 2017 trial identifier NCT03016910.

Clinical implications of 18F-sodium fluoride uptake in subclinical aortic valve calcification: Its relation to coronary atherosclerosis and its predictive value

BackgroundUptake of 18F-sodium fluoride (18F-NaF) on positron emission tomography (PET) reflects active calcification. Application of this technique in the early phase of aortic valve calcification (AVC) is of clinical interest. We investigated clinical implications of 18F-NaF uptake in subclinical AVC evaluated simultaneously with coronary atherosclerosis, and the utility of 18F-NaF uptake in predicting AVC progression. MethodsWe studied 25 patients with subclinical AVC and coronary plaques detected on computed tomography (CT) who underwent 18F-NaF PET/CT. AVC score, volume, mean density, and the presence of high-risk coronary plaque were evaluated on CT in each patient. Focal 18F-NaF uptake in AVC and in coronary plaques was quantified with the maximum tissue-to-background ratio (TBRmax). ResultsThere were positive correlations between AVC TBRmax (A-TBRmax) and AVC parameters on CT. The 14 patients with high-risk coronary plaque had significantly higher A-TBRmax than those without such plaque (1.60 ± 0.18 vs 1.42 ± 0.13, respectively; P = 0.012). A-TBRmax positively correlated with maximum TBRmax of coronary plaque per patient (r = 0.55, P = 0.0043). In the 11 patients who underwent follow-up CT scan, A-TBRmax positively correlated with subsequent increase in AVC score (r = 0.74, P = 0.0091). ConclusionOur 18F-NaF PET- and CT-based data indicate relationships between calcification activity in subclinical AVC and characteristics of coronary atherosclerosis. 18F-NaF PET may provide new information regarding molecular conditions and future progression of subclinical AVC.

The presence of adverse atherosclerotic coronary plaque features is associated with diabetes

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The grant was given to the Bioimaging field of Semmelweis University by the Excellence Program of the Ministry of Innovation and Technology in Hungary. On Behalf of Cardiovascular Imaging Research Group (CIRG) Introduction Diabetes mellitus (DM) is associated with increased cardiovascular morbidity and mortality. However, there is a lack of data about the prevalence of high-risk coronary artery plaques in patients with DM. Purpose In our study we aimed to compare the prevalence of adverse atherosclerotic coronary artery plaque features between patients with and without DM. Methods We have analyzed the data of patients who underwent coronary computed tomography angiography (CCTA) between October 2012 and December 2020. Our exclusion criteria were coronary anomaly, congenital or other structural heart disease, previous revascularization or heart transplantation, non-diagnostic image quality and no available data on the presence of DM. Patients were divided into two groups based on the presence of DM. Results In total, 11357 patients (47.6% men) were included in our study. Prevalence of DM was 14.5%. There were significant differences in age (63.2 ± 9.5 vs 58.1 ± 12.2 years, p &amp;lt; 0.001) and major cardiovascular risk factors such as hypertension, dyslipidemia and smoking between the two groups (all p &amp;lt; 0.05). We have measured higher coronary artery calcium score in patients with DM vs. without DM (424.3 ± 744.0 vs 174.2 ± 794.6, p &amp;lt; 0.001). Luminal stenosis &amp;gt;70% was more frequent in the DM group (24.6% vs 10.5%, p &amp;lt; 0.001). While 29.6% of patients without DM had at least one high risk plaque, this rate was 38.9% in those with DM (positive remodeling: 19.6% vs 26.1%, low attenuation: 7.6% vs 10.2%, spotty calcium: 16.9% vs 21.6%, napkin-ring sign: 1.7% vs 2.6%, all p &amp;lt; 0.05). Conclusions The prevalence of severe coronary artery stenosis and coronary plaques with adverse characteristics was higher in patients with DM.

Effects of the PCSK9 antibody alirocumab on coronary atherosclerosis in patients with acute myocardial infarction: a serial, multivessel, intravascular ultrasound, near-infrared spectroscopy and optical coherence tomography imaging study–Rationale and design of the PACMAN-AMI trial

The risk for cardiovascular adverse events after acute myocardial infarction (AMI) remains high despite potent medical treatment including low-density lipoprotein cholesterol (LDL-C) lowering with statins. Proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies substantially reduce LDL-C when added to statin. Alirocumab, a monoclonal antibody to PCSK9, reduces major adverse cardiovascular events after AMI. The effects of alirocumab on coronary atherosclerosis including plaque burden, plaque composition and fibrous cap thickness in patients presenting with AMI remains unknown. To determine the effect of LDL-C lowering with alirocumab on top of high-intensity statin therapy on intravascular ultrasound (IVUS)-derived percent atheroma volume (PAV), near-infrared spectroscopy (NIRS)-derived maximum lipid core burden index within 4 mm (maxLCBI4 mm) and optical coherence tomography (OCT)-derived fibrous cap thickness (FCT) in patients with AMI. In this multicenter, double-blind, placebo-controlled trial, 300 patients with AMI (ST-elevation or non-ST-elevation myocardial infarction) were randomly assigned to receive either biweekly subcutaneous alirocumab (150 mg) or placebo beginning <24 hours after the acute event as add-on therapy to rosuvastatin 20 mg. Patients undergo serial IVUS, NIRS and OCT in the two non-infarct related arteries at baseline (at the time of treatment of the culprit lesion) and at 52 weeks. The primary endpoint, change in IVUS-derived PAV, and the powered secondary endpoints, change in NIRS-derived maxLCBI4 mm, and OCT-derived minimal FCT, will be assessed 52 weeks post randomization. The PACMAN-AMI trial will determine the effect of alirocumab on top of high-intensity statin therapy on high-risk coronary plaque characteristics as assessed by serial, multimodality intracoronary imaging in patients presenting with AMI. NCT03067844.

The correlation between hepatic fat fraction evaluated by dual-energy computed tomography and high-risk coronary plaques in patients with non-alcoholic fatty liver disease.

To determine the relationship between non-alcoholic fatty liver disease (NAFLD) evaluated by a hepatic fat fraction (HFF) using dual-energy computed tomography (DECT) and high-risk coronary plaques (HRP) in NAFLD patients. We conducted a matched case-control study involving 172 NAFLD individuals recruited from August 2019 to September 2020. They underwent dual-energy coronary computed tomographic angiography and were classified as no-plaque, HRP negative and HRP positive groups. HFF values were measured using multimaterial decomposition algorithm of DECT, and the differences among three groups were compared. Multiple logistic regression analysis was performed to determine the independent correlation between HFF and HRP. Spearmanrankcorrelation was used to assess the correlations between HFF and multiple variables. HRP positive group (15.3%) had higher HFF values than no-plaque (6.9%) and HRP negative groups (8.9%) (P < 0.001). After adjusting for confounding variables, the results indicated that HFF was an independent risk factor for HRP (OR 1.93, P < 0.001). Additionally, HFF significantly correlated with coronary artery calcium score, hepatic CT attenuation, epicardial and pericoronary adipose tissue volume, and CT attenuation (all P < 0.001). As a new imaging marker for the quantification of liver fat, HFF was independently associated with HRP.

Metabolic syndrome and its factors are associated with noncalcified coronary burden in psoriasis: An observational cohort study

Psoriasis is associated with a heightened risk of cardiovascular disease and higher prevalence of metabolic syndrome. Investigate the effect of metabolic syndrome and its factors on early coronary artery disease assessed as noncalcified coronary burden by coronary computed tomography angiography in psoriasis. This cross-sectional study consisted of 260 participants with psoriasis and coronary computed tomography angiography characterization. Metabolic syndrome was defined according to the harmonized International Diabetes Federation criteria. Of the 260 participants, 80 had metabolic syndrome (31%). The metabolic syndrome group had a higher burden of cardiometabolic disease, systemic inflammation, noncalcified coronary burden, and high-risk coronary plaque. After adjusting for Framingham risk score, lipid-lowering therapy, and biologic use, metabolic syndrome (β=.31; P<.001) and its individual factors of waist circumference (β=.33; P<.001), triglyceride levels (β=.17; P=.005), blood pressure (β=.18; P=.005), and fasting glucose (β=.17; P=.009) were significantly associated with noncalcified coronary burden. After adjusting for all other metabolic syndrome factors, blood pressure and waist circumference remained significantly associated with noncalcified coronary burden. Observational nature with limited ability to control for confounders. In psoriasis, individuals with metabolic syndrome had more cardiovascular disease risk factors, systemic inflammation, and noncalcified coronary burden. Efforts to increase metabolic syndrome awareness in psoriasis should be undertaken to reduce the heightened cardiovascular disease risk.

Potential Application of Cardiac Computed Tomography for Early Detection of Coronary Atherosclerosis: From Calcium Score to Advanced Atherosclerosis Analysis.

In the present article, an overview of advanced analysis of coronary atherosclerosis by coronary computed tomography angiography (CCTA) is provided, focusing on the potential application of this technique in a primary prevention setting. Coronary artery calcium score (CACS) has a well-demonstrated prognostic value even in a primary prevention setting; however, fibro-fatty, high-risk coronary plaque may be missed by this tool. On the contrary, even if not recommended for primary prevention in the general population, CCTA may enable early high-risk atherosclerosis detection, and specific subgroups of patients may benefit from its application. However, further studies are needed to determine the possible use of CCTA in a primary prevention setting.

New carotid plaque, but not the progression of intima-media thickness, predicts the progression of high-risk coronary plaque.

Carotid intima-media thickness (CIMT) is regarded as a controversial risk marker for cardiovascular disease (CVD). We aimed to evaluate the role of CIMT and carotid plaque progression as predictors for the progression of coronary plaque and compositions. In the Garlic 4 study, asymptomatic patients with intermediate CVD risk (Framingham risk score 6-20%) were recruited for a serial carotid ultrasound, and coronary artery calcium score (CAC)/coronary computed tomography angiography (CCTA) studies for subclinical atherosclerosis at a baseline and 1 year. The association between progression of quantitatively measured coronary plaque compositions and the progression of CIMT/carotid plaque was analyzed. A P value <0.05 is considered as statistically significant. Forty-seven consecutive patients were included. The mean age was 58.5 ± 6.6 years, and 69.1 % were male. New carotid plaque appeared in 34.0 % (n = 16) of participants, and 55.3 % (n = 26) of subjects had coronary plaque progression. In multilinear regression analysis, adjusted by age, gender, and statin use, the development of new carotid plaque was significantly associated with an increase in noncalcified coronary plaque [β (SE) 2.0 (0.9); P = 0.025] and necrotic core plaque (1.7 (0.6); P = 0.009). In contrast, CIMT progression was not associated with the progression of coronary plaque, or coronary artery calcium (CAC) (P = NS). Compared to CIMT, carotid plaque is a better indicator of coronary plaque progression. The appearance of a new carotid plaque is associated with significant progression of necrotic core and noncalcified plaque, which are high-risk coronary plaque components.

Macrophage targeted theranostic strategy for accurate detection and rapid stabilization of the inflamed high-risk plaque.

Rationale: Inflammation plays a pivotal role in the pathogenesis of the acute coronary syndrome. Detecting plaques with high inflammatory activity and specifically treating those lesions can be crucial to prevent life-threatening cardiovascular events.Methods: Here, we developed a macrophage mannose receptor (MMR)-targeted theranostic nanodrug (mannose-polyethylene glycol-glycol chitosan-deoxycholic acid-cyanine 7-lobeglitazone; MMR-Lobe-Cy) designed to identify inflammatory activity as well as to deliver peroxisome proliferator-activated gamma (PPARγ) agonist, lobeglitazone, specifically to high-risk plaques based on the high mannose receptor specificity. The MMR-Lobe-Cy was intravenously injected into balloon-injured atheromatous rabbits and serial in vivo optical coherence tomography (OCT)-near-infrared fluorescence (NIRF) structural-molecular imaging was performed.Results: One week after MMR-Lobe-Cy administration, the inflammatory NIRF signals in the plaques notably decreased compared to the baseline whereas the signals in saline controls even increased over time. In accordance with in vivo imaging findings, ex vivo NIRF signals on fluorescence reflectance imaging (FRI) and plaque inflammation by immunostainings significantly decreased compared to oral lobeglitazone group or saline controls. The anti-inflammatory effect of MMR-Lobe-Cy was mediated by inhibition of TLR4/NF-κB pathway. Furthermore, acute resolution of inflammation altered the inflamed plaque into a stable phenotype with less macrophages and collagen-rich matrix.Conclusion: Macrophage targeted PPARγ activator labeled with NIRF rapidly stabilized the inflamed plaques in coronary sized artery, which could be quantitatively assessed using intravascular OCT-NIRF imaging. This novel theranostic approach provides a promising theranostic strategy for high-risk coronary plaques.

Relationship between high shear stress and OCT-verified thin-cap fibroatheroma in patients with coronary artery disease.

High-risk coronary plaques have been considered predictive of adverse cardiac events. Both wall shear stress (WSS) in patients with hemodynamically significant lesions and optical coherence tomography (OCT) -verified thin-cap fibroatheroma (TCFA) are associated with plaque rupture, the most common underlying mechanism of acute coronary syndrome. The aim of the study was to test the hypothesis that invasive coronary angiography-based high WSS is associated with the presence of TCFA detected by OCT in obstructive lesions. From a prospective study of patients who underwent OCT examination for angiographically obstructive lesions (Yellow II), we selected patients who had two angiographic projections to create a 3-dimensional reconstruction model to allow assessment of WSS. The patients were divided into 2 groups according to the presence and absence of TCFA. Mean WSS was assessed in the whole lesion and in the proximal, middle and distal segments. Of 70 patients, TCFA was observed in 13 (19%) patients. WSS in the proximal segment (WSSproximal) (10.20 [5.01, 16.93Pa]) and the whole lesion (WSSlesion) (12.37 [6.36, 14.55Pa]) were significantly higher in lesions with TCFA compared to WSSproximal (5.84 [3.74, 8.29Pa], p = 0.02) and WSSlesion (6.95 [4.41, 11.60], p = 0.04) in lesions without TCFA. After multivariate analysis, WSSproximal was independently associated with the presence of TCFA (Odds ratio 1.105; 95%CI 1.007-1.213, p = 0.04). The optimal cutoff value of WSSproximal to predict TCFA was 6.79 Pa (AUC: 0.71; sensitivity: 0.77; specificity: 0.63 p = 0.02). Our results demonstrate that high WSS in the proximal segments of obstructive lesions is an independent predictor of OCT-verified TCFA.

High-Risk Coronary Plaque Regression After Intensive Lifestyle Intervention in Nonobstructive Coronary Disease: A Randomized Study

ObjectivesThe authors sought to study the impact of diet and lifestyle intervention on changes in atherosclerotic plaque volume and composition. BackgroundLifestyle and diet modification are the leading strategies to manage coronary artery disease; however, their direct impact on atherosclerosis remains unknown. Coronary plaque composition is related to the risk of future cardiovascular events independent of stenosis severity and can be conveniently evaluated with computed tomography angiography (CTA). MethodsWe enrolled 92 patients (41% women; mean age 60 ± 7.7 years) with nonobstructive (<70% stenosis) coronary atherosclerosis identified by CTA. Participants were randomized (1:1) to either the DISCO (Dietary Intervention to Stop Coronary Atherosclerosis in Computed Tomography) intervention group (systematic follow-up by a dietitian to adhere to the Dietary Approaches to Stop Hypertension nutrition model together with optimal medical therapy [OMT]) or the control group (OMT alone). In all patients, CTA was repeated after 66.9 ± 13.7 weeks. The outcome was change (Δ) in atheroma volume and plaque composition. Based on atherosclerotic tissue attenuation ranges in Hounsfield units (HU), the following components of coronary plaque were distinguished: dense calcium (>351 HU), fibrous plaque (151 to 350 HU), and fibrofatty plaque combined with necrotic core (-30 to 150 HU), referred to as noncalcified plaque. ResultsPercent atheroma volume increased in the control arm (Δ = +1.1 ± 3.4%; p = 0.033) versus no significant change in the experimental arm (Δ = +1.0% ± 4.2%; p = 0.127; intergroup p = 0.851). There was a reduction in noncalcified plaque in both the experimental arm (Δ = −51.3 ± 79.5 mm3 [−1.7 ± 2.7%]; p < 0.001) and the control arm (Δ = −21.3 ± 57.7 [−0.7 ± 1.9%]; p = 0.018), which was greater in the DISCO intervention group (intergroup p = 0.045). No differences in fibrous component or dense calcium changes were observed between the groups. ConclusionsControlled diet and lifestyle intervention together with OMT may slow the progression of atherosclerosis and reduce noncalcified plaque volume compared to OMT alone. (Dietary Intervention to Stop Coronary Atherosclerosis in Computed Tomography [DISCO-CT]; NCT02571803)

Triglyceride to HDL-cholesterol ratio is a predictor of future coronary events: a possible role of high-risk coronary plaques detected by coronary CT angiography

Abstract Background For the prevention of future cardiovascular events, control of residual risks such as triglyceride rich lipoproteins and HDL-cholesterol is an emerging problem beyond LDL-cholesterol. Triglyceride to HDL-cholesterol ratio (TG/HDL ratio) has been reported to be useful for risk classification of cardiovascular diseases. Meanwhile, several studies showed that high-risk plaque characteristics evaluated with coronary CT angiography (cCTA) was associated with the incidence of acute coronary syndrome. However, the relationship of TG/HDL ratio with coronary plaque characteristics and its impact of this association on future coronary events have not been fully elucidated. Purpose The aim of this study was to evaluate the association between TG/HDL ratio and high-risk plaque detected by cCTA and its impact on future coronary events. Methods A total of 944 patients suspected stable coronary artery disease who underwent cCTA at our institution were analyzed (mean 64-year-old, 55% male). Patients were divided into two groups by the median value of TG/HDL ratio (higher TG/HDL: TG/HDL ratio ≥2.0, lower TG/HDL: TG/HDL ratio &amp;lt;2.0). Coronary high-risk plaques were defined as a plaque with all three components; low attenuation plaque (&amp;lt;50H.U.), positive remodeling (remodeling index &amp;gt;1.1) and spotty calcification. Cardiovascular event was defined as cardiovascular death, acute coronary syndrome, and late coronary revascularization after 30 days of CT acquisition. Results The higher TG/HDL ratio was significantly associated with male gender (63% vs. 48%, P&amp;lt;0.001), body mass index (24.8±3.8 vs. 22.9±4.0, p&amp;lt;0.001), the prevalence of hypertension (65% vs. 54%, P&amp;lt;0.001), dyslipidemia (60% vs. 42%, P&amp;lt;0.001), diabetes mellitus (38% vs. 27%, P=0.001) and current smoking (26% vs. 10%, p&amp;lt;0.001). Regarding cCTA findings, the prevalence of significant stenosis, calcified plaque, non-calcified plaque, coronary plaques with low attenuation plaque, positive remodeling and spotty calcification in the higher TG/HDL group were greater than those in the lower group (Figure 1A). Of note, the difference in high-risk plaque between two groups was significant. (18% vs. 11%, p=0.004). Multivariate logistic analysis revealed that the TG/HDL ratio was an independent risk factor for high-risk plaque even after adjustment (OR, 1.35; 95% CI, 1.01–1.81; p=0.049). Regarding coronary events (median follow-up duration; 48 months), Kaplan-Meier curve showed poor event-free rate in the higher TG/HDL group (Figure 1B). At Cox proportional hazard analysis, higher TG/HDL ratio (HR, 1.94; 95% CI, 1.01–3.70; p=0.046) and CT-verified high-risk plaque (HR, 2.36; 95% CI, 1.27–4.38; p=0.006) were independent predictive factors for coronary events even after adjustment. Conclusion TG/HDL ratio is involved in the vulnerability of CT-verified coronary plaque characteristics. This association may play an important role in the prognostic impact of TG/HDL ratio on future cardiovascular events. Funding Acknowledgement Type of funding source: None

Higher oxidized high-density lipoprotein to apolipoprotein A-I ratio is associated with high-risk coronary plaque characteristics determined by CT angiography

BackgroundOxidized high-density lipoprotein (oxHDL), unlike native HDL, is characterized by reduced cholesterol efflux capability and anti-inflammatory properties. The ratio of oxHDL to apolipoprotein A-I (oxHDL/apoAI) is a possible marker of dysfunctional HDL. The aim of this study was to evaluate the association between oxHDL/apoAI and coronary plaque characteristics that increase the likelihood of cardiovascular events as determined by coronary computed tomography (CT) angiography. MethodsA total of 297 patients (mean age; 67 years, men; 63%) who underwent coronary CT angiography for suspected stable coronary artery disease (CAD) were included. High-risk plaques (HRP) were defined by three characteristics: positive remodeling; low-density plaques; and spotty calcification. Significant stenosis was defined as a luminal narrowing of >70%. Serum concentrations of oxHDL were measured using an enzyme-linked immunosorbent assay. ResultsPatients with higher oxHDL/ApoAI showed significantly greater prevalence of HRP (p = 0.03) and significant stenosis (p < 0.01) compared with patients with low oxHDL/ ApoAI. The multivariate logistic analysis demonstrated that oxHDL/ApoAI significantly associated with the presence of HRP and significant coronary stenosis (p = 0.01 and < 0.01). In the follow-up study including 243 patients for a median period of 1.8 years, univariate cox regression analysis showed that oxHDL/ApoAI, HRP and significant stenosis were significant predictors of cardiovascular events. ConclusionsA high oxHDL/apoAI was associated with the presence of HRP and significant stenosis determined by coronary CT angiography, which can lead to cardiovascular events in patients with suspected stable CAD.

Pathological Features of Ruptured Coronary Plaque and Thrombus Interfaces: Fibrin and von Willebrand Factor as Platelet Scaffolds on Rupture Sites.

Arterial thrombus formation is thought to be initiated by platelet adhesion to the subendothelial matrix, but ruptured atherosclerotic plaques are characterized by substantial reduction of matrix proteins compared with stable plaques. Intraplaque erythrocytes and/or fibrin have been reported in high-risk coronary plaques. The aims of the current study were to identify factors that provide scaffolds for platelets at the sites of ruptured coronary plaques and investigate depositions of iron and bilirubin as hemoglobin catabolites in the ruptured plaques. Histological characteristics of plaque components and the thrombus interface were examined in 73 acute coronary aspirated thrombi. Necrotic debris (95%), macrophages (95%), and cholesterin clefts (81%) were observed frequently at the ruptured plaque and thrombus interface. A fibrous matrix (47%), calcification (32%), and extracellular deoxyribonucleic acid (15%) were identified as small foci. Tissue factor was localized in the necrotic core and macrophages. Fibrin and von Willebrand factor were consistently deposited within the plaques and beneath platelet aggregations. The citrullinated histone H3-immunopositive area accounted for only 0.5% of the plaque area. Bilirubin and iron depositions were detected in approximately 20% of the plaques in addition to biliverdin reductase and ferritin expression in macrophages. Fibrin and von Willebrand factor rather than matrix proteins and neutrophil extracellular traps may be major adhesive molecules at the sites of ruptured plaques. Iron and bilirubin deposits may be markers for rupture-prone plaques.

Treatment of Psoriasis With Biologic Therapy Is Associated With Improvement of Coronary Artery Plaque Lipid-Rich Necrotic Core: Results From a Prospective, Observational Study.

Lipid-rich necrotic core (LRNC), a high-risk coronary plaque feature assessed by coronary computed tomography angiography, is associated with increased risk of future cardiovascular events in patients with subclinical, nonobstructive coronary artery disease. Psoriasis is a chronic inflammatory condition that is associated with increased prevalence of high-risk coronary plaque and risk of cardiovascular events. This study characterized LRNC in psoriasis and how LRNC modulates in response to biologic therapy. Consecutive biologic naïve psoriasis patients (n=209) underwent coronary computed tomography angiography at baseline and 1-year to assess changes in LRNC using a novel histopathologically validated software (vascuCAP Elucid Bioimaging, Boston, MA) before and after biologic therapy over 1 year. Study participants were middle-aged, predominantly male with similar cardiometabolic and psoriasis status between treatment groups. In all participants at baseline, LRNC was associated with Framingham risk score (β [standardized β]=0.12 [95% CI, 0.00-0.15]; P=0.045), and psoriasis severity (β=0.13 [95% CI, 0.01-0.26]; P=0.029). At 1-year, participants receiving biologic therapy had a reduction in LRNC (mm2; 3.12 [1.99-4.66] versus 2.97 [1.84-4.35]; P=0.028), while those who did not receive biologic therapy over 1 year demonstrated no significant change with nominally higher LRNC (3.12 [1.82-4.60] versus 3.34 [2.04-4.74]; P=0.06). The change in LRNC was significant compared with that of the nonbiologic treated group (ΔLRNC, -0.22 mm2 versus 0.14 mm2, P=0.004) and remained significant after adjusting for cardiovascular risk factors and psoriasis severity (β=-0.09 [95% CI, -0.01 to -0.18]; P=0.033). LRNC was associated with psoriasis severity and cardiovascular risk factors in psoriasis. Additionally, there was favorable modification of LRNC in those on biologic therapy. This study provides evidence of potential reduction in LRNC with treatment of systemic inflammation. Larger, longer follow-up prospective studies should be conducted to understand how changes in LRNC may translate into a reduction in future cardiovascular events in psoriasis.

Relationship between interleukin-1β gene expression in epicardial adipose tissue and coronary atherosclerosis based on computed tomographic analysis

BackgroundAnti-inflammatory therapy targeting interleukin (IL)-1β reduced cardiovascular events in a randomized trial. We evaluated the relationship between IL-1β mRNA expression in epicardial adipose tissue (EAT) and clinically-assessed coronary atherosclerosis on computed tomography (CT). MethodsWe studied 45 patients before cardiac surgery (coronary artery bypass grafting [CABG], n ​= ​18; non-CABG, n ​= ​27). EAT volume, the coronary calcium score (CCS), and the presence of non- and/or partially-calcified coronary plaques (NCPs) and high-risk coronary plaques (HRPs; minimum CT density <30 Hounsfield units and vascular remodeling index >1.1) on CT angiography were assessed. EAT samples were obtained during cardiac surgery. IL-1β mRNA expression in EAT was measured using quantitative real-time PCR and normalized to that of β-actin in each patient. ResultsThere was no difference in IL-1β mRNA levels between patients who were scheduled for CABG and non-CABG surgery or among subgroups based on the CCS. However, patients with NCPs (median [interquartile range], 4.1[2.0-11.6]E-4 versus 1.8[0.6-4.5]E-4, p ​= ​0.024) and HRP (7.6[3.0-20.4]E-4 versus 1.9[0.7-4.3]E-4, p ​= ​0.0023) had higher IL-1β mRNA levels than those without these plaques. On multivariate analysis adjusted for age, sex, coronary risk factors, statin therapy, CCS, and EAT volume, the presence of HRPs was significantly correlated with elevated IL-1β mRNA levels in EAT (β ​= ​0.39, p ​= ​0.047). ConclusionOur data suggest a contribution of EAT to coronary atherosclerosis through molecular behavior, such as IL-1β gene expression, which may be a new therapeutic target.

High-risk coronary plaque in SLE: low-attenuation non-calcified coronary plaque and positive remodelling index

BackgroundPositive remodelling index and presence of low-attenuation non-calcified plaque (LANCP) are characteristic vessel changes in unstable coronary plaques. We sought to characterise these high-risk plaque features in patients with systemic...

Positron emission tomographic studies of the association between atherogenesis and aortitis among psoriatic patients.

There is increased interest in the use of positron emission tomography (PET) in psoriatic patients. We used PET induced with tracer fluorine-18 (18F) fluorodeoxyglucose (FDG) to study the association between the process of early-atherogenesis (eAg) and aortitis by quantifying enhanced aortic vascular inflammation along with calculation of total coronary plaque load (TCPL) and non-calcified atherosclerotic plaque load (NcAPL). In order to study the utility of aortitis in capturing eAg, we also assessed luminal stenosis atherosclerosis (LSA) and high-risk coronary plaques (HrCP). The study was conducted at our hospital between 1 April 2014 and 31 December 2017, and the analysis was done in July 2018. We recruited 180 consecutive psoriatic patients and subjected them to 18F-FDG PET. However, in order to characterise eAg, 160 out of 180 patients were also subjected to coronary angiographic computed tomographic studies (CACTS). Among 180 psoriatic patients (76 women, 42%) (mean [SD] age, 51.1 [13.2] years), greater prevalence values of LSA (odd ratio [OR], 3.71; 95% confidence interval [CI], 1.84-7.89; p = 0.001) and HrCP (OR, 3.11; 95% CI: 1.54-6.51; p = 0.003) along with enhanced TCPL (standardised β = 0.44; p < 0.001) were observed in patients with enhanced aortitis. However, the association between aortitis and HrCP was controlled by low-attenuation plaque (LAP), while the same between aortitis and TCPL was controlled by NcAPL (β = 0.45; p < 0.001). Association between aortitis and broad coronary angiographic indices was achieved and hence predicted the possibility of a surrogate role of aortitis in eAg.

Prevalence of high-risk coronary plaques in patients with and without metabolic syndrome and the relationship with prognosis

BackgroundMetabolic syndrome (MS) is a disorder, characterized by clusters of cardiovascular risk factors such as central obesity, insulin resistance, dyslipidemia and hypertension. Patients with MS may have a higher plaque burden that increases their risk of major adverse cardiovascular events (MACEs). This study aimed to analyze the prevalence of high-risk coronary plaques in patients with and without MS by coronary computed tomography angiography (CCTA) and to investigate the relationship between MS, high-risk coronary plaques, and their prognosis.MethodsThis was a retrospective cohort study of 1136 patients who underwent CCTA due to chest pain without obstructive heart disease (≥50% coronary stenosis) between January 2014 and December 2015 in our hospital. The relationships between high risk coronary plaques, MS, and other clinical factors were assessed. Multicollinearity analysis was performed to identify the collinearity between the variables. The proportional hazard assumption was checked and using Schoenfeld residual test. Cox proportional hazards model and Kaplan-Meier survival analysis assessed the relationship between MS, high-risk coronary plaques and MACEs.ResultsHigh-risk plaques were more frequent in the MS group than non-MS group (P = 0.004). MS (HR = 2.128, 95%CI: 1.524–2.970, P < 0.001), presence of high-risk plaques (HR = 11.059, 95%CI: 7.749–57.232, P < 0.001) and high sensitivity C-reactive protein (hsCRP) (HR = 1.629, 95%CI: 1.128–2.352, P = 0.009) were related with an increased risk of MACEs in patients with risk factors for coronary heart disease. In patients with high-risk plaques, MS (HR = 2.265, 95%CI: 1.629–3.150, P < 0.001) and hsCRP (HR = 1.267, 95%CI: 1.191–1.348, P = 0.004) were related with an increased risk of MACEs. Kaplan-Meier analysis showed differences in MACEs between the MS and non-MS groups in the whole population and those with high-risk plaques (both P < 0.0001).ConclusionsHigh-risk plaques were more common in patients with MS. MS and the presence of high-risk plaques were independent risk factors for MACEs.