Sex Differences in Plaque Composition and Morphology Among Symptomatic Patients With Mild-to-Moderate Carotid Artery Stenosis

Background and Purpose: Incidence of ischemic stroke differs between men and women, with substantially higher rates in men. The underlying mechanism of this difference remains poorly understood but may be because of differences in carotid atherosclerosis. Using an in-depth imaging-based approach, we investigated differences between carotid plaque composition and morphology in male and female patients with stroke, taking into account differences in total plaque burden. Additionally, we investigated all possible within-artery combinations of plaque characteristics to explore differences between various plaque phenotypes. Methods: We included 156 men and 68 women from the PARISK (Plaque At Risk) study, a prospective cohort study of patients with recent ischemic cerebrovascular symptoms and <70% ipsilateral carotid stenosis. Plaque characteristics (intraplaque hemorrhage [IPH], lipid-rich necrotic core [LRNC], calcifications, thin-or-ruptured fibrous cap, ulcerations, total plaque volume) were assessed with magnetic resonance imaging and multidetector-row computed tomography angiography. We used multivariable logistic and linear regression analyses to assess sex differences in plaque characteristics. Results: We found significant difference in total plaque volume between men and women (β=22.9 mm 3 [95% CI, 15.4–30.5]; mean volume in men 1399±425 mm 3 , in women 1011±242 mm 3 ). Additionally, men were more likely to have IPH (odds ratio [OR]=2.8 [95% CI, 1.3–6.3]; IPH proportion in men 49%, in women 16%) and LRNC (OR=2.4 [95% CI, 1.2–4.7]; LRNC proportion in men 73%, in women 41%) even after adjustment for total plaque volume. We found no sex-specific differences in plaque volume-corrected volumes of IPH, LRNC, and calcifications. In terms of coexistence of plaque characteristics, we found that men had more often a plaque with coexistence of calcifications, LRNC, and IPH (OR=2.7 [95% CI, 1.2–7.0]), with coexistence of thin-or-ruptured fibrous cap/ulcerations, LRNC, and IPH (OR=2.4 [95% CI, 1.1–5.9]), and with coexistence of all plaque characteristics (OR=3.0 [95% CI, 1.2–8.6]). Conclusions: In symptomatic patients with mild-to-moderate carotid stenosis, men are more likely to have a high-risk carotid plaque with IPH and LRNC than women, regardless of total plaque burden. Men also have more often a plaque with multiple vulnerable plaque components, which could comprise an even higher stroke risk. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01208025.

Effects of statin therapy on coronary plaque volume by decreasing CRP/hsCRP levels: A meta-regression of randomized controlled trials

Background and aims: Several clinical trials have indicated that statins stabilize and reverse atherosclerotic plaque. However, different studies have provided inconsistent findings regarding mechanisms and influencing factors of plaque regression under statin therapy. In this study, meta-analysis and meta-regression were used to determine the effect of statin medication on coronary plaque volume as determined by intravenous ultrasound. Meanwhile, the impact of statins on CRP/hsCRP reduction on plaque regression was discussed. Methods: Up to May 28, 2021, a systematic PubMed, EMBASE, and Cochrane search was performed for randomized controlled trials that assessed treatment effect using total atheroma volume (TAV), percent atheroma volume (PAV), or plaque volume (PV). Only CRP/hsCRP and LDL-C values reported before and after treatment were considered. Results: 12 studies fulfilled the inclusion criteria and were included in the systematic review. Compared with control groups, meta-analysis of 15 statin-treated arms reported change of TAV/PV showed standardized mean difference (SMD) at -0.27 (95% confidence intervals [CI]: -0.42, -0.12). Meta-analysis of 7 studies reported change of PAV revealed SMD at -0.16 (95% CI: -0.29, -0.03). Meta-regression analysis revealed percent change of CRP/hsCRP statistically influences SMD in change of TAV/PVafter adjusting for percent change of LDL-C, age and gender. Meta-regression analysis showed that percent change of CRP/hsCRP statistically influences SMD in change of PAV. Conclusion: In conclusion, statin therapy is beneficial for plaque regression. Statins promote plaque regression through their anti-inflammatory ability while lowering LDL-C is unaffected. Keywords: Statins; Reduction of atherosclerosis; C-reactive protein; Randomized controlled trial; Meta-analysis

Variability of the Plasma Lipidome and Subclinical Coronary Atherosclerosis

Objective: While the risk of acute coronary events has been associated with biological variability of circulating cholesterol, the association with variability of other atherogenic lipids remains less understood. We evaluated the longitudinal variability of 284 lipids and investigated their association with asymptomatic coronary atherosclerosis. Approach and Results: Circulating lipids were extracted from fasting blood samples of 83 community-sampled symptom-free participants (age 41–75 years), collected longitudinally over 6 months. Three types of coronary plaque volume (calcified, lipid-rich, and fibrotic) were quantified using computed tomography coronary angiogram. We first deconvoluted between-subject (CV g ) and within-subject (CV w ) lipid variabilities. We then tested whether the mean lipid abundance was different across groups categorized by Framingham risk score and plaques phenotypes (lipid-rich, fibrotic, and calcified). Last, we investigated whether visit-to-visit variability of each lipid was associated with plaque burden. Most lipids (72.5%) exhibited higher CV g than CV w . Among the lipids (N=145) with 1.2-fold higher CV g than CV w , 26 species including glycerides and ceramides were significantly associated with Framingham risk score and the 3 plaque phenotypes (false discovery rate <0.05). In an exploratory analysis of person-specific visit-to-visit variability without multiple-comparisons testing, high variability of 3 lysophospholipids (lysophosphatidylcholines 16:0, 18:0, and O-18:1) were associated with lipid-rich and fibrotic (noncalcified) plaque volume while high variability of diacylglycerol 18:1_20:0, triacylglycerols 52:2, 52:3, and 52:4, ceramide d18:0/20:0, dihexosylceramide d18:1/16:0, and sphingomyelin 36:3 were associated with calcified plaque volume. Conclusions: High person-specific longitudinal variation of specific nonsterol lipids are associated with the burden of subclinical coronary atherosclerosis. Larger studies are needed to confirm these exploratory findings.

Radiation dose reduction with deep-learning image reconstruction for coronary computed tomography angiography

Objectives Deep-learning image reconstruction (DLIR) offers unique opportunities for reducing image noise without degrading image quality or diagnostic accuracy in coronary CT angiography (CCTA). The present study aimed at exploiting the capabilities of DLIR to reduce radiation dose and assess its impact on stenosis severity, plaque composition analysis, and plaque volume quantification. Methods This prospective study includes 50 patients who underwent two sequential CCTA scans at normal-dose (ND) and lower-dose (LD). ND scans were reconstructed with Adaptive Statistical Iterative Reconstruction-Veo (ASiR-V) 100%, and LD scans with DLIR. Image noise (in Hounsfield units, HU) and quantitative plaque volumes (in mm3) were assessed quantitatively. Stenosis severity was visually categorized into no stenosis (0%), stenosis (< 20%, 20–50%, 51–70%, 71–90%, 91–99%), and occlusion (100%). Plaque composition was classified as calcified, non-calcified, or mixed. Results Reduction of radiation dose from ND scans with ASiR-V 100% to LD scans with DLIR at the highest level (DLIR-H; 1.4 mSv vs. 0.8 mSv, p < 0.001) had no impact on image noise (28 vs. 27 HU, p = 0.598). Reliability of stenosis severity and plaque composition was excellent between ND scans with ASiR-V 100% and LD scans with DLIR-H (intraclass correlation coefficients of 0.995 and 0.974, respectively). Comparison of plaque volumes using Bland–Altman analysis revealed a mean difference of − 0.8 mm3 (± 2.5 mm3) and limits of agreement between − 5.8 and + 4.1 mm3. Conclusion DLIR enables a reduction in radiation dose from CCTA by 43% without significant impact on image noise, stenosis severity, plaque composition, and quantitative plaque volume. Key Points •Deep-learning image reconstruction (DLIR) enables radiation dose reduction by over 40% for coronary computed tomography angiography (CCTA). •Image noise remains unchanged between a normal-dose CCTA reconstructed by ASiR-V and a lower-dose CCTA reconstructed by DLIR. •There is no impact on the assessment of stenosis severity, plaque composition, and quantitative plaque volume between the two scans.

Quantification of the Brain Multiple Sclerosis (MS) Plaque Volume: Comparison of Quantitative and Qualitative Assessments of the Brain MS Plaque Volume in Successive Magnetic Resonance Images before and after Medication Use

Background: Multiple sclerosis (MS) is a demyelinating disease with multiple symptoms. To examine the effect of medications, magnetic resonance imaging (MRI) imaging can be performed. Objectives: This study aimed to compare the visual assessment of MRI images by physicians and the results of a MATLAB-based software developed for evaluating the MS plaque volume. Methods: TYSABRI (natalizumab)-treated patients were enrolled in this study. MRI was performed before and after treatment. A MATLAB-based software was developed to evaluate the MRI images. The images were then subjectively evaluated by three specialists and objectively assessed by the software, and the results were then compared. Results: Thirty-five patients participated in this study. According to the software, the status of 37.14% of the patients improved; however, 62.86% of cases deteriorated after a year of treatment. There was less than 50% agreement between the physicians and less than 55% agreement between the physicians and the software results. A disagreement of almost 45% was observed between the physicians and the software results, as in some cases, small changes were detected in successive images. The second cause of disagreement could be the physicians’ expectations; although the patient’s recovery was highly expected in some cases, their condition deteriorated. Conclusions: The results revealed that the objective assessment of sequential MRI images of MS patients reduced human errors and improved the evaluation of this disease.

Correlation Analysis of Huayu Tongmai Decoction Intervention and Prognosis Indexes of Patients with Carotid Atherosclerosis

Background. Carotid atherosclerosis (CAS) is a common disease which seriously threatens the health of senile patients. The studies have indicated that traditional Chinese medicine (TCM) may effectively improve the symptom of CAS, while the therapeutic effect of Huayu Tongmai decoction on CAS remains unclear. Thus, this study aimed to explore the correlation between traditional Chinese medicine Huayu Tongmai decoction intervention and prognosis indexes of patients with CAS. Methods. Ninety CAS patients admitted to Zibo TCM-Integrated Hospital from September 2018 to September 2020 were selected as the research object and randomly divided into the control group and the observation group according to the male-female ratio of 1 : 1. Patients in the control group accepted the atorvastatin intervention, and on this basis, patients in the observation group were further intervened with TCM Huayu Tongmai decoction. Before and after treatment, patients’ levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) were measured by the enzyme photometric colorimetry; hypersensitive c-reactive protein (hs-CRP) levels were measured by the ELISA method; nitric oxide (NO) levels were measured by the nitrate reductase assay and endothelin-1 (ET-1) levels were measured by radioimmunoassay; and the right and left carotid internal diameter (CAD), intima-media thickness (IMT), and plaque volume were measured by carotid ultrasonography. Results. The TC, TG, and LDL-C levels significantly decreased in patients compared to those before intervention; compared with the control group, patients who accepted Huayu Tongmai decoction combined with atorvastatin saw more significant improvement in their blood lipid indexes ( P < 0.01 ); after intervention, patients’ hs-CRP and ET-1 levels dropped significantly while the NO level rose remarkably, and between the two groups, the improvement in levels of hs-CRP, ET-1, and NO of patients in the observation group was significantly better ( P < 0.01 ); it was concluded from the imaging diagnosis results that compared with using atorvastatin alone, the combined intervention could better improve patients’ CAD, IMT, and plaque volume. Conclusion. Huayu Tongmai decoction can effectively improve patients’ blood lipid, reduce inflammatory response, enhance levels of relevant regulatory factors of CAS, and alleviate the symptoms.

Diagnostic Efficacy of CCTA And CT-FFR Based On Risk Factors For Myocardial Ischemia

Background: Coronary artery CCTA can observe the degree of coronary artery stenosis and FFR can evaluate the physiological function of coronary artery. However, noninvasive imaging examination that can both observe the above two methods at the same time has not yet been elucidated.Objective: To investigate the diagnostic efficacy of coronary computed tomography angiography (CCTA) and computed tomography-derived fractional flow reserve (CT-FFR) based on different risk factors for myocardial ischemia.Methods: Patients undergoing CCTA in our hospital from August 18, 2020 to April 28, 2021 were randomly selected, and the data were subjected to CT-FFR analysis. Vascular characteristics were measured, including total plaque volume, calcified plaque volume, non-calcified plaque volume, plaque length, and lumen stenosis, and the patients were categorized into a non-ischemia group (FFR>0.8) and an ischemia group (FFR≤0.8). Plaque characteristics were compared between the two groups, and logistic regression analysis was employed to explore the correlations between plaque characteristics and ischemic lesions.Results: From a total of 122 patients enrolled in the study, there were 218 vascular branches with FFR>0.8 and 174 vascular branches with FFR≤0.8. There were significant group differences in total plaque volume, calcified plaque volume, plaque length, and lumen stenosis >50% (n). The obtained data were as follows: non-ischemic group 10.57 (4.80, 259.65), ischemic group 14.87 (3.39, 424.45), Z=9.772, p=0.002, non-ischemic group 10.57 (0, 168.77), ischemic group 14.87 (0, 191.00), Z=2.503，p≤0.001), non-ischemic group 8.17 (37.05, 40.53), ischemic group 8.38 (56.66, 86.47), Z=5.923, p=0.016, and lumen stenosis >50%, non-ischemic group 46, ischemic group 90, x2=14.77，p≤0.001. The regression analysis results indicated that total plaque volume, calcified plaque volume, plaque length and lumen stenosis >50% were risk factors for myocardial ischemia, with ORs and p values of (2.311, p=0.002), (1.021, p=0.004), (2.159, p<0.001), and (0.181, p<0.001), respectively.Conclusion: Total plaque volume, calcified plaque volume, plaque length and lumen stenosis >50% are predictors for myocardial ischemia. Coronary artery CCTA combined with CT-FFR could simultaneously observe the anatomical stenosis and evaluate myocardial blood supply at the functional level. Thus, myocardial ischemia could be better diagnosed.

Epicardial adipose tissue volume is associated with low-attenuation plaque volume in subjects with or without increased visceral fat: a 3-vessel coronary artery analysis with CT angiography

Background Low-attenuation plaque (LAP) with a CT value of less than or equal 30 HU on coronary CT angiography (CCTA) is a marker of high-risk plaque features that leads to future acute coronary syndromes. Perivascular and epicardial adipose tissue (EAT) have been shown to be associated with progression of high-risk coronary plaques through metabolic and inflammatory mechanisms. However, association of EAT with LAP volume in three coronary arteries in subjects with or without visceral obesity remain unclear. Aims This study aimed to investigate the association of EAT volume (EAV) and coronary 3-vessel LAP volume in subjects with or without visceral obesity who underwent CCTA. Methods Patients who underwent CCTA without known coronary artery disease were included in the study (525 patients). Study subjects were classified as having non-obstructive or obstructive coronary artery disease according to the degree of coronary artery stenosis on CCTA. The plaque volume and EAV of the main vessel of the left anterior descending artery, left circumflex artery, and right coronary artery were measured with VINCENT software. Coronary plaque composition was classified as calcified plaque (CP, &gt;150HU), noncalcified plaque (NCP, 30–150HU), and Lap (&lt;30HU). The %LAP volume of the three coronary arteries was classified into quartiles. Multiple logistic regression analysis was used to analyze the factors associated with the %LAP volume. Results Compared with subjects without increase visceral fat, subjects with increased visceral fat had a significantly higher BMI, a greater total plaque volume, a greater total %LAP volume, a greater EAV, and a lower mean CT value of EAT. A significant correlation was observed between EAV and %LAP volume (R=0.24, p&lt;0.001). EAV (odds ratio; 1.83, 95% confidence interval 1.071–3.141, p-value 0.027) and type 2 diabetes mellitus (odds ratio 1.76, 95%confidence interval 1.042–3.000, p-value 0.034) appeared to be independent predictors of %LAP volume (Q4), when adjusted by age, gender, BMI&gt;25 kg/m2, visceral fat &gt;100cm2, LogCRP, coronary artery calcium score&gt;300, and obstructive coronary artery disease requiring revascularization. Conclusion This study suggests that LAP volume, which reflects the high-risk plaques in the three coronary arteries, is associated with EAV in subjects with or without increased visceral fat. Further research is needed whether pharmacological therapeutic intervention enables the prevention of coronary plaque progression and destabilization through the reduction of EAV in patients. FUNDunding Acknowledgement Type of funding sources: None.

Independent predictors of major cardiovascular events as quantitatively assessed by coronary CT-angiography: a long-term follow-up analysis

Introduction Quantitative CT coronary angiography using semi-automated software provides detailed information about plaque volume and high-risk plaque characteristics, beyond traditional measures like diameter stenosis. We assessed the potential value of plaque quantity and morphology to independently predict MACE in a cohort with long-term follow up. Methods In this secondary analysis of 301 symptomatic patients undergoing coronary CTA at baseline, total plaque volume (TPV), non-calcified- (NCPV), calcified- (CPV) and vulnerable coronary plaque volume (in mm3), diameter stenosis (in %) and remodeling index were quantified using semi-automated software (Autoplaque version 2.5, Cedars-Sinai Medical Center, Los Angeles, CA). Patients were followed for major cardiovascular events (MACE), defined as a composite of cardiovascular death, myocardial infarction and coronary revascularization. Optimal thresholds for each quantitative CTA measure were computed using CART-algorithm (Classification and Regression Trees). Results Complete follow-up was available for 234 (78%) patients. The mean age was 59±10 years. Over a median follow-up of 10.7 years, the composite outcome occurred in 34 (15%) patients (5 patients with cardiovascular death, 6 with myocardial infarction, 26 with revascularization). Patients experiencing MACE had more frequently hypertension (p=0.03) and a higher Framingham risk score (p=0.002). Survival anaylsis using cox proportional hazard ratios showed significant univariate associations between MACE and TPV (HR 5.16; 95% CI 1.58–16.89; p=0.007), NCPV (HR 4.83; 95% CI 1.45–15.81; p=0.009), CPV (HR 2.86; 95% CI 1.39–5.86; p=0.004), vulnerable plaque volume (HR 3.35; 95% CI 1.52–7.41; p=0.003), diameter stenosis (HR 5.19; 95% CI 2.64–10.22; p&lt;0.001) and remodeling index (HR 4.24; 95% CI 2.03–8.86; p&lt;0.001). In multivariable cox regression analysis diameter stenosis (HR 3.70; 95% CI 1.72–7.93; p=0.001) and remodeling index (HR 2.69; 95% CI 1.19–6.09; p=0.018) remained significant independent predictors of MACE, adjusted for Framingham risk score (HR 2.56; 95% CI 1.26–5.22; p=0.010), however plaque volume and plaque subcomponents did not. Conclusion On long term follow-up, remodeling index and coronary diameter stenosis obtained by quantitative coronary CT angiography independently predicted MACE on multivariable assessment. More comprehensive plaque assessment algorithms including plaque volume as well as plaque subcomponents were significantly associated with MACE in univariate, but not multivariate analysis after adjustment for diameter stenosis and remodeling index. FUNDunding Acknowledgement Type of funding sources: None.