Coronary Plaque Characteristics Research Articles

Aggravating effect of abnormal low-density protein cholesterol level on coronary atherosclerotic plaque in type 2 diabetes mellitus patients assessed by coronary computed tomography angiography

BackgroundThe abnormal low-density protein cholesterol (LDL-C) level in the development of atherosclerosis is often comorbid in individuals with type 2 diabetes mellitus(T2DM). This study aimed to investigate the aggravating effect of abnormal LDL-C levels on coronary artery plaques assessed by coronary computed tomography angiography (CCTA) in T2DM.Materials and methodsThis study collected 3439 T2DM patients from September 2011 to February 2022. Comparative analysis of differences in coronary plaque characteristics was performed for the patients between the normal LDL-C level group and the abnormal LDL-C level group. Factors with P < 0.1 in the univariable linear regression analyses were included in the multivariable linear stepwise regression.ResultsA total of 2820 eligible T2DM patients were included and identified as the normal LDL-C level group (n = 973) and the abnormal LDL-C level group (n = 1847). Compared with the normal LDL-C level group, both on a per-patient basis and per-segment basis, patients with abnormal LDL-C level showed more calcified plaques, partially calcified plaques, low attenuation plaques, positive remodellings, and spotty calcifications. Multivessel obstructive disease (MVD), nonobstructive stenosis (NOS), obstructive stenosis (OS), plaque involvement degree (PID), segment stenosis score (SSS), and segment involvement scores (SIS) were likely higher in the abnormal LDL-C level group than that in the normal LDL-C level group (P < 0.001). In multivariable linear stepwise regression, the abnormal LDL-C level was validated as an independent positive correlation with high-risk coronary plaques and the degree and extent of stenosis caused by plaques (low attenuation plaque: β = 0.116; positive remodelling: β = 0.138; spotty calcification: β = 0.091; NOS: β = 0.427; OS: β = 0.659: SIS: β = 1.114; SSS: β = 2.987; PID: β = 2.716, all P value < 0.001).ConclusionsAbnormal LDL-C levels aggravate atherosclerotic cardiovascular disease (ASCVD) in patients with T2DM. Clinical attention deserves to be caught by the tailored identification of cardiovascular risk categories in T2DM individuals and the achievement of the corresponding LDL-C treatment goal.

Type 2 diabetes mellitus aggravates coronary atherosclerosis in hypertensive individuals based on coronary CT angiography: a retrospective propensity score-based study.

The effect of type 2 diabetes mellitus (T2DM) on coronary atherosclerosis detected on coronary computed tomography angiography (CCTA) in hypertensive patients has attracted increasing attention. This study investigated the relationships of T2DM with coronary artery plaque characteristics and semiquantitative CCTA scores in hypertensive patients. In this single-center study, 1,700 hypertensive patients, including 850 T2DM [HT(T2DM+)] and 850 non-T2DM [HT(T2DM-)] individuals, were retrospectively analyzed after propensity matching. Plaque type, extent, coronary stenosis, segment involvement score (SIS), segment stenosis score (SSS), and CT-based Leaman score (CT-LeSc) based on CCTA were assessed and compared between the two groups. HT(T2DM+) patients had more coronary segments with calcified plaque (2.08 ± 2.20 vs. 1.40 ± 1.91), mixed plaque (2.90 ± 2.87 vs. 2.50 ± 2.66), nonobstructive stenosis (4.23 ± 2.44 vs. 3.62 ± 2.42), and obstructive stenosis (1.22 ± 2.18 vs. 0.78 ± 1.51), a lower proportion of 1-vessel disease (15.3% vs. 25.5%), a higher proportion of 3-vessel disease (59.6% vs. 46.7%), and higher SIS (5.5 ± 3.1 vs. 4.4 ± 3.0), SSS (10.3 ± 8.5 vs. 7.7 ± 7.1), and CT-LeSc (9.4 ± 5.6 vs. 7.9 ± 5.2) than HT(T2DM-) patients (all P-values <0.05). Multivariable analysis revealed that T2DM was an independent risk factor for calcified plaque [odds ratio (OR) = 2.213], obstructive coronary artery disease (CAD) (OR = 1.271), multivessel disease (OR = 1.838), SIS > 4 (OR = 1.910), SSS > 6 (OR = 1.718), and CT-LeSc > 5 (OR = 1.584) in hypertension population (all P-values <0.05). T2DM was independently associated with the presence of calcified coronary artery plaque and increased the risk of obstructive CAD, multivessel disease, and CT-LeSc > 5 in hypertensive patients. More attention should be given to the assessment and management for coronary atherosclerosis in hypertensive patients with T2DM, as this population may have a higher risk of cardiovascular events.

Impact of endothelial shear stress on coronary atherosclerotic plaque progression and composition: A meta-analysis and systematic review

Background and aimsIntracoronary pressure gradients and translesional flow patterns have been correlated with coronary plaque progression and lesion destabilization. In this study, we aimed to determine the relationship between endothelial shear stress and plaque progression and to evaluate the effect of shear forces on coronary plaque features. MethodsA systematic review was conducted in medical on-line databases. Selected were studies including human participants who underwent coronary anatomy assessment with computational fluid dynamics (CFD)-based wall shear stress (WSS) calculation at baseline with anatomical evaluation at follow-up. A total of six studies were included for data extraction and analysis. ResultsThe meta-analysis encompassed 31′385 arterial segments from 136 patients. Lower translesional WSS values were significantly associated with a reduction in lumen area (mean difference −0.88, 95% CI −1.13 to −0.62), an increase in plaque burden (mean difference 4.32, 95% CI 1.65 to 6.99), and an increase in necrotic core area (mean difference 0.02, 95% CI 0.02 to 0.03) at follow-up imaging. Elevated WSS values were associated with an increase in lumen area (mean difference 0.78, 95% CI 0.34 to 1.21) and a reduction in both fibrofatty (mean difference −0.02, 95% CI −0.03 to −0.01) and fibrous plaque areas (mean difference −0.03, 95% CI −0.03 to −0.03). ConclusionThis meta-analysis shows that WSS parameters were related to vulnerable plaque features at follow-up. These results emphasize the impact of endothelial shear forces on coronary plaque growth and composition. Future studies are warranted to evaluate the role of WSS in guiding clinical decision-making.

Effect of statins on severity of coronary artery lesion and clinical prognosis in patients with coronary heart disease

To investigate the effect of statins on the severity of coronary artery lesion in patients with coronary heart disease, and to analyze the risk factors of clinical prognosis. A retrospective cohort study was conducted. The clinical data of 156 patients with coronary heart disease and completed the second re-examination of coronary CT angiography (CCTA) who were admitted to the department of cardiovascular medicine of Peking University People's Hospital from January 2017 to December 2021 were collected. According to whether they took statins regularly according to the doctor's instructions after being diagnosed with coronary heart disease based on the first CCTA examination, the patients were divided into statin group and non-statin group, and the clinical characteristics of the two groups and the results of the second re-examination of CCTA were compared and analyzed. According to whether the patients had major adverse cardiovascular and cerebrovascular events (MACCE) within 3-5 years after diagnosis of coronary heart disease, the patients were divided into MACCE group and non-MACCE group, and the clinical characteristics of the two groups were compared and analyzed. Multivariate Logistic regression analysis was used to screen the risk factors related to the adverse prognosis (occurrence of MACCE) of patients with coronary heart disease. (1) A total of 156 patients with coronary heart disease were enrolled, including 113 patients (72.44%) in the statin group and 43 patients (27.56%) in the non-statin group. Except for low density lipoprotein (LDL) and serum creatinine (SCr), there was no significant difference in gender, age, body mass index (BMI), basic diseases, smoking history, the first CCTA display of coronary artery lesions and plaque characteristics, the interval between the two CCTA and other laboratory indicators between the two groups. Compared with the non-statin group, the statin group had a significant reduction in the overall increase rate of coronary artery stenosis score (Gensini score) in the CCTA re-examination and the incidence of MACCE [Gensini score increase rate: 25.66% (29/113) vs. 46.51% (20/43), incidence of MACCE: 9.73% (11/113) vs. 30.23% (13/43), both P < 0.05]. (2) Among 156 patients with coronary heart disease, 24 cases (15.38%) experienced MACCE within 3-5 years after diagnosis, while 132 cases (84.62%) did not experience MACCE. The proportion of patients in the MACCE group who regularly took statins after diagnosis was significantly lower than that in the non-MACCE group [45.83% (11/24) vs. 77.27% (102/132), P < 0.01], and D-dimer and glycosylated hemoglobin (HbA1c) were significantly higher than those in the non-MACCE group [D-dimer (μg/L): 148.50 (101.25, 314.75) vs. 88.10 (59.03, 132.12), HbA1c: 6.45% (6.20%, 7.93%) vs. 6.10% (5.81%, 6.92%), both P < 0.05]. Compared with the non-MACCE group, in the first CCTA examination of patients in the MACCE group, the total percentage of atheroma volume (PAV), fibrous-fat PAV, necrotic core PAV and Gensini score were significantly increased [total PAV: 43.05% (29.19%, 60.60%) vs. 24.57% (16.94%, 39.09%), fibrous-fat PAV: 18.61% (8.48%, 26.44%) vs. 6.81% (4.16%, 12.57%), necrotic core PAV: 5.96% (2.98%, 8.71%) vs. 2.29% (1.47%, 4.36%), Gensini score: 30.25 (23.50, 38.30) vs. 19.50 (13.20, 31.10), all P < 0.05]. Multivariate Logistic regression analysis showed that regular use of statins [odds ratio (OR) = 0.282, 95% confidence interval (95%CI) was 0.110-0.727, P = 0.008], D-dimer (OR = 1.011, 95%CI was 1.005-1.017, P < 0.001), necrotic core PAV (OR = 1.323, 95%CI was 1.120-1.563, P = 0.001) and Gensini score (OR = 1.038, 95%CI was 1.004-1.073, P = 0.028) were independent risk factors for MACCE within 3-5 years after diagnosis in patients with coronary heart disease. For patients with coronary heart disease, D-dimer, necrotic core PAV, and Gensini scores should be closely monitored. Statins can effectively alleviate the severity of coronary artery disease and reduce the occurrence of MACCE in patients with coronary artery disease.

Evaluation of fractional flow reserve and atherosclerotic plaque characteristics on coronary non-contrast T1-weighted magnetic resonance imaging

Background and aimsThe relationship between high-risk coronary plaque characteristics regardless of the severity of lesion stenosis and myocardial ischemia remains unsettled. High-intensity plaques (HIPs) on non-contrast T1-weighted magnetic resonance imaging (T1WI) have been characterized as high-risk coronary plaques. We sought to elucidate whether the presence of coronary HIPs on T1WI influences fractional flow reserve (FFR) in the distal segment of the vessel. MethodsWe retrospectively analyzed 281 vessels in 231 patients with chronic coronary syndrome who underwent invasive FFR measurement and coronary T1WI using a multicenter registry. The plaque-to-myocardial signal intensity ratio (PMR) of the most stenotic lesion was evaluated; a coronary plaque with PMR ≥1.4 was defined as a HIP. ResultsThe median PMR of coronary plaques on T1WI in vessels with FFR ≤0.80 was significantly higher than that of plaques with FFR >0.80 (1.17 [interquartile range (IQR): 0.99–1.44] vs. 0.97 [IQR: 0.85–1.09]; p < 0.001). Multivariable analysis showed that an increase in PMR of the most stenotic segment was associated with lower FFR (beta-coefficient, −0.050; p < 0.001). The presence of coronary HIPs was an independent predictor of FFR ≤0.80 (odds ratio (OR), 6.18; 95% confidence interval (CI), 1.93–19.77; p = 0.002). Even after adjusting for plaque composition characteristics based on computed tomography angiography, the presence of coronary HIPs was an independent predictor of FFR ≤0.80 (OR, 4.48; 95% CI, 1.19–16.80; p = 0.026). ConclusionsCoronary plaques with high PMR are associated with low FFR in the corresponding vessel, indicating that plaque morphology might influence myocardial ischemia severity.

Screening, risk stratification and CT imaging for assessment of coronary artery disease

Early treatment of cardiovascular risk factors and characterization of coronary plaques is essential to collect prognostic information about coronary artery disease (CAD) and prevent cardiovascular events. Discussion of the most important risk factors of CAD, basic diagnostic of CAD, prevention, and prognostic factors of CAD with focus on cardiac computed tomography (CT). Prevalence and prognostic impact of CAD risk factors; description of specific assessment of risk profiles; estimation of pretest probability; conventional prevention of CAD; prognostic assessment of CAD using the Calcium Scoring and coronary CT angiography. Assessment of risk profiles and estimation of pretest probability for obstructive coronary stenosis necessitates athorough evaluation of medical history and laboratory values. The composition and extent of calcified and noncalcified plaques in CT exams based on the criteria of the Coronary Artery Disease-Reporting and Data System give important prognostic information about the risk of cardiovascular events, which increases with high plaque burden and vice versa. Initial imaging with CT for evaluation of CAD leads to areduction of invasive coronary angiographies and catheter-associated complications. Besides early detection of cardiovascular risk factors, the additional assessment of plaque burden and significant stenosis in CT gives further prognostic information to facilitate effective therapies to prevent cardiovascular events and in the case of low plaque burden avoid invasive coronary angiography. However, systmatic screening using Calcium Scoring is not established yet due to insufficient data, although it could potentially be used for an early risk stratification in patients with multiple risk factors.

Pathological Characteristics and Classification of Unstable Coronary Atherosclerotic Plaques.

Important forensic diagnostic indicators of sudden death in coronary atherosclerotic heart disease, such as acute or chronic myocardial ischemic changes, sometimes make it difficult to locate the ischemic site due to the short death process, the lack of tissue reaction time. In some cases, the deceased died of sudden death on the first-episode, resulting in difficulty for medical examiners to make an accurate diagnosis. However, clinical studies on coronary instability plaque revealed the key role of coronary spasm and thrombosis caused by their lesions in sudden coronary death process. This paper mainly summarizes the pathological characteristics of unstable coronary plaque based on clinical medical research, including plaque rupture, plaque erosion and calcified nodules, as well as the influencing factors leading to plaque instability, and briefly describes the research progress and technique of the atherosclerotic plaques, in order to improve the study on the mechanism of sudden coronary death and improve the accuracy of the forensic diagnosis of sudden coronary death by diagnosing different pathologic states of coronary atherosclerotic plaques.

Increased prevalence of high-risk coronary plaques in metabolic dysfunction associated stetatotic liver disease patients: A meta-analysis.

Metabolic dysfunction associated steatotic liver disease (MASLD) is associated with an increased risk of coronary artery disease. Computed Tomography Coronary Angiography (CTCA) can assess both the extent and the features of coronary plaques. We aimed to gather evidence about the prevalence and features of coronary plaques among MASLD patients. PubMed, Scopus, and Google Scholar databases were searched for randomized controlled trials and adjusted observational studies assessing the prevalence and features of coronary plaques by means of CTCA in MASLD patients as compared with a control group. The prevalence of coronary stenosis (defined as >30% and >50% diameter of stenosis), of increasing coronary artery calcium (CAC) score and of high-risk features (namely low-attenuation plaques, napkin ring sign, spotty calcification and positive remodelling) in MASLD patients were the endpoints of interest. Twenty-four observational studies were included. MASLD was associated with an increased prevalence of critical coronary stenosis compared with controls (odds ratio [OR] 1.54, 95%CI 1.23-1.93). Increased values of CAC score were observed in MASLD patients (OR 1.35, 95%CI 1.02-1.78 and OR 2.26, 95%CI 1.57-3.23 for CAC score 0-100 and >100, respectively). An increased risk of 'high-risk' coronary plaques was observed in MASLD patients (OR 2.13, 95%CI 1.42-3.19). As high-risk features plaques, a higher prevalence of positive remodelling and spotty calcification characterize MASLD patients (OR 2.92, 95%CI 1.79-4.77 and OR 2.96, 95%CI 1.22-7.20). Patients with MASLD are at increased risk of developing critical coronary stenosis and coronary plaques characterized by high-risk features as detected by CTCA.

Prognostic implications of pre-transcatheter aortic valve replacement computed tomography-derived coronary plaque characteristics and stenosis severity.

The study aimed to investigate the prognostic value of pre-transcatheter aortic valve replacement (TAVR) computed tomography angiography (CTA) in assessing physiological stenosis severity (CTA-derived fractional flow reserve (CT-FFR)) and high-risk plaque characteristics (HRPC). Among TAVR patients who underwent pre-procedure CTA, the presence and number of HRPCs (minimum lumen area of < 4 mm2, plaque burden ≥ 70%, low-attenuating plaques, positive remodeling, napkin-ring sign, or spotty calcification) as well as CT-FFR were assessed. The risk of vessel-oriented composite outcome (VOCO, a composite of vessel-related ischemia-driven revascularization, vessel-related myocardial infarction, or cardiac death) was compared according to the number of HRPC and CT-FFR categories. Four hundred and twenty-seven patients (68.4% were male) with 1072 vessels were included. Their mean age was 70.6 ± 10.6years. Vessels with low CT-FFR (≤ 0.80) (41.7% vs. 15.8%, adjusted hazard ratio (HRadj) 1.96; 95% confidence interval (CI): 1.28-2.96; p = 0.001) or lesions with ≥ 3 HRPC (38.7% vs. 16.0%, HRadj 1.81; 95%CI 1.20-2.71; p = 0.005) demonstrated higher VOCO risk. In the CT-FFR (> 0.80) group, lesions with ≥ 3 HRPC showed a significantly higher risk of VOCO than those with < 3 HRPC (34.7% vs. 13.0%; HRadj 2.04; 95%CI 1.18-3.52; p = 0.011). However, this relative increase in risk was not observed in vessels with positive CT-FFR (≤ 0.80). In TAVR candidates, both CT-FFR and the presence of ≥ 3 HRPC were associated with an increased risk of adverse clinical events. However, the value of HRPC differed with the CT-FFR category, with more incremental predictability among vessels with negative CT-FFR but not among vessels with positive CT-FFR. In transcatheter aortic valve replacement (TAVR) candidates, pre-TAVR CTA provided the opportunity to assess coronary physiological stenosis severity and high-risk plaque characteristics, both of which are associated with worse clinical outcomes. • The current study investigated the prognostic value of coronary physiology significance and plaque characteristics in transcatheter aortic valve replacement patients. • The combination of coronary plaque vulnerability and physiological significance showed improved accuracy in predicting clinical outcomes in transcatheter aortic valve replacement patients. • Pre-transcatheter aortic valve replacement CT can be a one-stop-shop tool for coronary assessments in clinical practice.

Artificial intelligence coronary computed tomography, coronary computed tomography angiography using fractional flow reserve, and physician visual interpretation in the per-vessel prediction of abnormal invasive adenosine fractional flow reserve

Abstract Aims A comparison of diagnostic performance comparing AI-QCTISCHEMIA, coronary computed tomography angiography using fractional flow reserve (CT-FFR), and physician visual interpretation on the prediction of invasive adenosine FFR have not been evaluated. Furthermore, the coronary plaque characteristics impacting these tests have not been assessed. Methods and results In a single centre, 43-month retrospective review of 442 patients referred for coronary computed tomography angiography and CT-FFR, 44 patients with CT-FFR had 54 vessels assessed using intracoronary adenosine FFR within 60 days. A comparison of the diagnostic performance among these three techniques for the prediction of FFR ≤ 0.80 was reported. The mean age of the study population was 65 years, 76.9% were male, and the median coronary artery calcium was 654. When analysing the per-vessel ischaemia prediction, AI-QCTISCHEMIA had greater specificity, positive predictive value (PPV), diagnostic accuracy, and area under the curve (AUC) vs. CT-FFR and physician visual interpretation CAD-RADS. The AUC for AI-QCTISCHEMIA was 0.91 vs. 0.76 for CT-FFR and 0.62 for CAD-RADS ≥ 3. Plaque characteristics that were different in false positive vs. true positive cases for AI-QCTISCHEMIA were max stenosis diameter % (54% vs. 67%, P &amp;lt; 0.01); for CT-FFR were maximum stenosis diameter % (40% vs. 65%, P &amp;lt; 0.001), total non-calcified plaque (9% vs. 13%, P &amp;lt; 0.01); and for physician visual interpretation CAD-RADS ≥ 3 were total non-calcified plaque (8% vs. 12%, P &amp;lt; 0.01), lumen volume (681 vs. 510 mm3, P = 0.02), maximum stenosis diameter % (40% vs. 62%, P &amp;lt; 0.001), total plaque (19% vs. 33%, P = 0.002), and total calcified plaque (11% vs. 22%, P = 0.003). Conclusion Regarding per-vessel prediction of FFR ≤ 0.8, AI-QCTISCHEMIA revealed greater specificity, PPV, accuracy, and AUC vs. CT-FFR and physician visual interpretation CAD-RADS ≥ 3.

Protruding Aortic Plaque and Coronary Plaque Vulnerability.

Protruding aortic plaque is known to be associated with an increased risk for future cardiac and cerebrovascular events. However, the relationship between protruding aortic plaque and coronary plaque characteristics has not been systematically investigated. A total of 615 patients who underwent computed tomography angiography, and preintervention optical coherence tomography imaging were included. Coronary plaque characteristics were compared to evaluate coronary plaque vulnerability in patients with protruding aortic plaque on computed tomography angiography. 615 patients, the 186 (30.2%) patients with protruding aortic plaque were older and had more comorbidities such as hypertension, chronic kidney disease, and a prior myocardial infarction than those without. They also had a higher prevalence of coronary plaques with vulnerable features such as thin-cap fibroatheroma (85 [45.7%] versus 120 [28.0%], P<0.001), lipid-rich plaque (165 [88.7%] versus 346 [80.7%], P=0.014), macrophages (147 [79.0%] versus 294 [68.5%], P=0.008), layered plaque (117 [62.9%] versus 213 [49.7%], P=0.002), and plaque rupture (96 [51.6%] versus 111 [25.9%], P<0.001). Patients with protruding aortic plaque experienced more major adverse cardiac and cerebrovascular events, including all-cause mortality, nonfatal acute coronary syndromes, and stroke (27 [14.7%] versus 21 [4.9%], P<0.001; 8 [4.3%] versus 1 [0.2%], P<0.001; 5 [2.7%] versus 3 [0.7%], P=0.030; and 5 [2.7%] versus 2 [0.5%], P=0.013, respectively). The current study demonstrates that patients with protruding aortic plaque have more features of coronary plaque vulnerability and are at increased risk of future adverse events.

Advanced CT measures of coronary artery disease with intermediate stenosis in patients with severe aortic valve stenosis.

Coronary artery disease (CAD) and severe aortic valve stenosis (AS) frequently coexist. While pre-transcatheter aortic valve replacement (TAVR) computed tomography angiography (CTA) allows to rule out obstructive CAD, interpreting hemodynamic significance of intermediate stenoses is challenging. This study investigates the incremental value of CT-derived fractional flow reserve (CT-FFR), quantitative coronary plaque characteristics (e.g., stenosis degree, plaque volume, and composition), and peri-coronary adipose tissue (PCAT) density to detect hemodynamically significant lesions among those with AS and CAD. We included patients with severe AS and intermediate coronary lesions (20-80% diameter stenosis) who underwent pre-TAVR CTA and invasive coronary angiogram (ICA) with resting full-cycle ratio (RFR) assessment between 08/16 and 04/22. CTA image analysis included assessment of CT-FFR, quantitative coronary plaque analysis, and PCAT density. Coronary lesions with RFR ≤ 0.89 indicated hemodynamic significance as reference standard. Overall, 87 patients (age 77.9 ± 7.4 years, 38% female) with 95 intermediate coronary artery lesions were included. CT-FFR showed good discriminatory capacity (area under receiver operator curve (AUC) = 0.89, 95% confidence interval (CI) 0.81-0.96, p < 0.001) to identify hemodynamically significant lesions, superior to anatomical assessment, plaque morphology, and PCAT density. Plaque composition and PCAT density did not differ between lesions with and without hemodynamic significance. Univariable and multivariable analyses revealed CT-FFR as the only predictor for functionally significant lesions (odds ratio 1.28 (95% CI 1.17-1.43), p < 0.001). Overall, CT-FFR ≤ 0.80 showed diagnostic accuracy, sensitivity, and specificity of 88.4% (95%CI 80.2-94.1), 78.5% (95%CI 63.2-89.7), and 96.2% (95%CI 87.0-99.5), respectively. CT-FFR was superior to CT anatomical, plaque morphology, and PCAT assessment to detect functionally significant stenoses in patients with severe AS. CT-derived fractional flow reserve in patients with severe aortic valve stenosis may be a useful tool for non-invasive hemodynamic assessment of intermediate coronary lesions, while CT anatomical, plaque morphology, and peri-coronary adipose tissue assessment have no incremental or additional benefit. These findings might help to reduce pre-transcatheter aortic valve replacement invasive coronary angiogram. • Interpreting the hemodynamic significance of intermediate coronary stenoses is challenging in pre-transcatheter aortic valve replacement CT. • CT-derived fractional flow reserve (CT-FFR) has a good discriminatory capacity in the identification of hemodynamically significant coronary lesions. • CT-derived anatomical, plaque morphology, and peri-coronary adipose tissue assessment did not improve the diagnostic capability of CT-FFR in the hemodynamic assessment of intermediate coronary stenoses.

Incremental prognostic value of coronary plaque features on CT angiography in symptomatic patients with obstructive CAD

Incremental prognostic value of coronary plaque features on CT angiography in symptomatic patients with obstructive CAD

Body mass index and characteristics of coronary plaque in younger patients with type 2 diabetes

Background and aimsThe association between the body mass index (BMI) and the characteristics of coronary plaque in younger type 2 diabetes (T2D) patients with coronary artery disease (CAD) remains to be elucidated. Methods and resultsA total of 138 consecutive younger (<65 years) T2D patients with CAD, who underwent optical coherence tomography imaging of the culprit lesion were included. The patients were classified into either the higher BMI group (n = 68) or the lower BMI group (n = 70) according to the median of BMI (25.9 kg/m2). The prevalence of thin-cap fibroatheroma (TCFA) (35.3 vs. 17.1 %, p = 0.015) was significantly higher in the higher BMI group than in the lower BMI group. The prevalence of TCFA was significantly higher in patients with higher BMI than in those with lower BMI among patients with hemoglobin A1c (HbA1c) ≥7.0 % (odds ratio [OR] 5.40, 95 % confidence interval [CI] 1.72–17.0, p = 0.003) although the significant difference was not observed among patients with HbA1c <7.0 % (OR 0.89, 95 % CI 0.25–3.13, p = 0.851). ConclusionHigher BMI was associated with a higher prevalence of TCFA in younger T2D patients with CAD, particularly in patients with HbA1c ≥ 7.0 %.

Relationship of Soluble Lectin-Like Low-Density Lipoprotein Receptor-1 (sLOX-1) With Inflammation and Coronary Plaque Progression in Psoriasis.

Psoriasis is a chronic inflammatory condition associated with coronary artery disease risk. Uptake of oxidized low-density lipoprotein by the lectin-like low-density lipoprotein receptor-1 triggers release of the soluble extracellular domain of the receptor (sLOX-1). We sought to characterize the relationship between sLOX-1, inflammation, and coronary plaque progression in psoriasis. A total of 327 patients with psoriasis had serum sLOX-1 levels measured at baseline by an ELISA-based assay. Stratification by high-sensitivity C-reactive protein ≥4.0 mg/L (quartile 4), identified 81 participants who had coronary plaque phenotyping at baseline and were followed longitudinally by coronary computed tomography angiography. Subjects within high-sensitivity C-reactive protein quartile 4 were middle-aged (51.47±12.62 years), predominantly men (54.3%) with moderate psoriasis disease severity (6.60 [interquartile range, 3.30-13.40]). In the study cohort, participants with sLOX-1 above the median displayed increased vulnerable coronary plaque features. At baseline, sLOX-1 was associated with total burden (rho=0.296; P=0.01), noncalcified burden (rho=0.286; P=0.02), fibro-fatty burden (rho=0.346; P=0.004), and necrotic burden (rho=0.394; P=0.002). A strong relationship between sLOX-1, noncalcified burden (β=0.19; P=0.03), and fibro-fatty burden (β=0.29; P=0.003) was found in fully adjusted models at baseline and 1- and 4-year follow-up. Finally, coronary plaque features progressed over 1 year regardless of biologic or systemic treatment in subjects with high sLOX-1. Patients with psoriasis with both high sLOX-1 and high-sensitivity C-reactive protein levels have increased coronary plaque burden associated with atherosclerotic plaque progression independent of biologic and systemic treatment. Thus, sLOX-1 might be considered as a promising marker in coronary artery disease risk estimation beyond traditional risk factors. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01778569.

A context-aware deep network for automated characterization of coronary artery plaque from coronary CT angiography

Abstract Background Identifying various types of plaque, including calcified, non-calcified, and mixed, can furnish crucial insights into a patient's susceptibility to cardiovascular disease and aid in making treatment decisions. Manual quantification of coronary artery plaque on coronary CT angiography (CCTA) poses several challenges, including subjectivity, time consumption, and potential measurement errors. Purpose Our objective was to develop a context-aware deep network (CADN) that could automatically evaluate coronary artery plaque in a sizable, multi-center prospective CCTA cohort. Methods The APOLLO study is a multi-center study involving CCTA scans of 5,000 Asian patients. At the present stage of this study, CCTA analysis was performed on a subset of 474 patients (138 females; mean age of 58 ± 11 years), of whom 76% were Chinese, 17% were Indian/Malay, and 7% were of other ethnicities. Additionally, 53% had hypertension, 20% had diabetes, 70% had hyperlipidemia, and 27% were obese. A total of 2,983 lesions in 1,422 arteries were analyzed, including 473 non-calcified, 1,612 mixed, and 898 calcified plaques. The CADN combines a 3D convolutional neural network with a Transformer and incorporates contextual information along with local features (Figure 1). The network was trained and tested in 379 and 95 patients, respectively. Results The CADN method showed a high level accuracy in detecting plaque, achieving a lesion-level area under the receiver operating characteristic curve of 0.87. Furthermore, the CADN method demonstrated a lesion-level diagnostic accuracy, F1 score, and intra-class correlation coefficient of 0.74, 0.71, and 0.90, respectively, in characterizing plaque into categories of no plaque, non-calcified, mixed, and calcified. When analyzing its performance in each coronary artery, the CADN method was able to accurately characterize the plaque into multiple categories in the LAD, LCX, and RCA with accuracies of 0.70, 0.73, and 0.77, respectively. Conclusion The context-aware deep network is a novel approach that demonstrates good diagnostic performance in detecting and characterizing coronary artery plaque.Figure 1.CADN for coronary plaque.

Simple patient and lesion characteristics on coronary angiography can accurately predict FFR-proven ischemia

Abstract Aims Fractional flow reserve (FFR) measured during invasive coronary angiography (ICA), the reference standard for diagnosing coronary ischemia, potentially risks pressure wire-induced arterial wall injury. We aimed to develop a model for diagnosing coronary ischemia based on simple patient and lesion characteristics without invasive intracoronary pressure measurement. Methods We performed quantitative coronary angiography (QCA) analyses on subjects who had undergone FFR measurements during clinically indicated ICA. Clinical, ICA and QCA variables were input into a prediction model for coronary ischemia, defined as FFR ≤0.8. Least absolute shrinkage and selection operator (LASSO) regression with internal ten-fold cross-validation was implemented using R software to minimize multicollinearity and select final model variables, i.e., those corresponding to the nadir of the binomial deviation plot. Per-vessel and per-subject results were reported. Results Among 103 subjects (mean age 61 ±10 years; 74 male, 29 female) recruited from hospitals in Singapore (participants in a prospective study NCT03054324) and China, we analyzed 148 stenotic vessels visually assessed diameter (DS) ≥30%. From a dataset comprising 37 variables including baseline clinical characteristics, coronary artery morphological parameters and plaque characteristics, LASSO selected six final model variables: lesion length, minimal lumen diameter, stenosis flow reserve, DS, systolic blood pressure and diabetes, negating serious multicollinearity. The first three variables were measured on QCA, the third using ICA images acquired at rest. Our model outperformed DS ≥70% for discriminating coronary ischemia at both per-vessel (area-under-curve [AUC] 0.907 vs 0.770, p&amp;lt;0.001) and per-subject levels (AUC 0.882 vs 0.759, p&amp;lt;0.001). Per-vessel model accuracy, sensitivity, specificity, positive and negative predictive values were 85.1%, 82.4%, 93.2%, 87.1% and 83.3%, respectively; and per-subject, 83.4%, 82.0%, 85.7%, 89.3% and 76.6%, respectively. Conclusion Compared with visual diameter assessment, our LASSO-based model attained superior prediction of FFR-defined coronary ischemia using an array of variables without the need for invasive pressure measurement.

Biomarkers for identification of high-risk coronary plaques in patients with suspected coronary artery disease

Abstract Background Patients with atherosclerotic plaques containing high-risk features have an increased likelihood of events and a worse prognosis. Whether elevated levels of biomarkers of ischemia e.g. TnI and inflammation e.g. high sensitive C-reactive protein (hsCRP) are associated with the presence of high-risk coronary atherosclerotic plaques (HRP) evaluated on coronary computed tomography angiography (CCTA) is not well described. Objectives To assess the association between 1) TnI and 2) hsCRP and quantified coronary plaque burden, luminal diameter stenosis and HRP in symptomatic patients with low/intermediate pre-test probability of obstructive coronary artery disease (CAD) referred to CCTA evaluation. Methods On enrolled patients (n=1,615), CCTA were analysed using a semiautomatic software for coronary artery plaque characterization. Patients with high (&amp;gt;6 ng/L) and low (&amp;lt;3 ng/L) TnI as well as high (&amp;gt;2 mg/L) and low (&amp;lt;1 mg/L) hsCRP were identified. Associations of high levels of TnI and hsCRP compared to low levels were investigated for the following: high plaque burden (defined as having total plaque volume above the 75th percentile on CCTA), presence of significant stenosis (defined as ≥50% luminal diameter stenosis on CCTA), and presence of HRP (defined as having a plaque with at least two risk features on CCTA). Results TnI and hsCRP were both positively correlated with total plaque burden (TnI rs=0.14, p&amp;lt;0.001; hsCRP rs=0.08, p&amp;lt;0.001). In multivariate logistic regression analyses, high TnI was when compared to low TnI associated with presence of stenosis (OR 1.43, 95% confidence interval (CI) 1.03-1.99, p=0.034), the presence of HRP (OR 1.79, 95% CI: 1.17– 2.74, p=0.008) and further the subtypes of HRP including low attenuation plaque (OR 1.93, 95% CI: 1.24–3.00, p=0.003) and positive remodelling (OR 1.51, 95% CI: 1.07–2.13, p=0.018). For high hsCRP levels, only the presence of stenosis and the HRP-subtype napkin ring sign correlated significantly. Conclusion In patients with suspected CAD TnI and hsCRP are associated with the presence of HRP features. These findings suggest that inflammatory and particularly ischemic biomarkers might improve early risk stratification and potentially also affect patient management.

Proteomics associated with coronary high-risk plaque features on optical coherence tomography

Abstract Introduction Cardiovascular disease is the major cause of death worldwide. The physiological status of the cardiovascular system is reflected in plasma proteins and a newly developed technique based on proximity extension assays has enabled the analysis of a broad range of protein biomarkers associated with cardiovascular disease. However, biomarkers for coronary high-risk plaques, including lipid-rich plaques, macrophages, cholesterol crystals, and microvessels, have not yet been found. Purpose This study aimed to identify proteins specific for coronary high-risk plaques. Methods We analyzed 57 patients (71.1 ± 10.6 years, male: 68.4%) who underwent intracoronary optical coherence tomography and provided blood samples for proteomic analysis. Forty-seven patients (86.0%) had lipid-rich plaques, 46 patients (80.7%) had macrophages, 16 patients (28.1%) had cholesterol crystals, and 27 patients (47.4%) had microvessels. A total of 1,470 plasma proteins were analyzed using the Olink® Explore 1,536 Reagent Kit and P2 100 cycle reagent kit on a NextSeq 2000 sequencer. Results In patients with lipid-rich plaques, the protein expressions of Interstitial collagenase (MMP1), Wiskott-Aldrich syndrome protein family member 1 (WASF1), and Protein phosphatase 1 regulatory subunit 12A (PPP1R12RA) were significantly increased, while the expressions of Fc receptor-like protein 3 (FCRL3), Folate receptor gamma (FOLR3), Cobalamin binding intrinsic factor (CBLIF), Glutathione S-transferase A1 (GSTA1), and Keratin, type I cytoskeletal 18 (KRT18) were significantly decreased (Figure A). In patients with macrophages, the protein expressions of MMP1, WASF1, PPP1R12RA, and Scavenger receptor cysteine-rich domain-containing group B protein (SSC4D) were significantly increased, while the expressions of Fatty acid-binding protein, intestinal (FABP2), FOLR3, CBLIF, GSTA1, and Fibroblast growth factor 21 (FGF21) were significantly decreased (Figure B). In patients with cholesterol crystals, the protein expressions of FOLR3, Secreted frizzled-related protein 1 (SFRP1), and Anterior gradient protein 2 homolog (AGR2) were significantly decreased (Figure C). In patients with microvessels, the expression of FOLR3 was significantly decreased (Figure D). Conclusion These proteins might be new biomarkers in patients with coronary high-risk plaques.

A specific molecular signature of extra-vesicles (EVs) was associated with cardiometabolic risk profile and atherosclerotic burden in patients with chronic coronary syndrome: a pilot study

Abstract Background microRNAs (miRs) are pivotal regulators of mRNA and protein expression. They critically contribute to cardiovascular pathophysiology and circulate in the blood using extra-vesicles (EVs) as delivery carrier. The role of EV-associated miRs in atherosclerotic cardiovascular disease, however, is unclear. Purpose The aim of this study was to detect Coronary Artery Disease (CAD)-related miRs carried by EVs in stable patients with Chronic Coronary Syndrome (CCS). In particular we aimed to assess whether a specific miRs signature is associated with the cardiometabolic risk profile and coronary atherosclerotic burden and plaque features, as evaluated by coronary computed tomography angiography (CTA) in these patients. Methods miRs with known effects in the cardiovascular system were analysed by real time-PCR in EVs isolated from CCS patients by density gradient centrifugation (n=21). All patients underwent coronary CTA to assess total, calcified, and noncalcified plaque volume (PV). Obstructive CAD was defined as the presence of stenoses &amp;gt;50% in at least one of the main coronary vessels. Results All CCS patients (n=21) were statin users and had coronary atherosclerosis documented by coronary CTA. Among the 25 miRs tested, 7 were detected within EVs and 4 of them, miR-145-5p, miR-30e5-p, miR-126-5p, miR-375, were significantly related with cardiometabolic profile, showing an alternative association with glucose and insulin, a positive correlation with HDL-Cholesterol and a negative correlation with triglycerides, BMI and waist circumference. No association was observed with Total-Cholesterol and LDL-Cholesterol (Figure1). These miRs were also not associated with the presence of obstructive CAD, but were significantly related with total, calcified, and noncalcified PVs (Figure1). Conclusions In CCS patients, among the 25 miRs studied and out of the 7 EV-associated, only 4 miRs were related with a specific cardiometabolic risk profile, characterized by insulin-resistance, obesity, high triglyceride and low HDL-Cholesterol levels. They were also associated with an increased coronary atherosclerotic burden. These results suggest a potential involvement of specific EV-associated miRs in molecular mechanisms of residual atherosclerotic risk.Figure 1