Total Plaque Volume Research Articles

Cardio-ankle vascular index is associated with coronary plaque composition assessed with iMAP-intravascular ultrasound in patients with coronary artery disease

BackgroundThe cardio-ankle vascular index (CAVI) is an indicator of arterial stiffness and has been reported to be associated with the severity of coronary artery disease and cardiovascular events. However, whether CAVI can predict the composition of coronary plaques remains unclear. MethodsWe enrolled 208 patients who underwent percutaneous coronary intervention (PCI) for culprit lesions evaluated with iMAP-intravascular ultrasound (IVUS), a radiofrequency imaging system for characterizing tissues. iMAP-IVUS classified the culprit plaque composition as fibrotic, lipidic, necrotic, or calcified, and the respective absolute volumes [fibrotic volume (FV), lipidic volume (LV), necrotic volume NV, and calcified volume] and their ratios (%) within the total plaque volume were calculated. A plaque with a median %NV of ≥ 33.2% was defined as a larger NV (LNV) plaque. We measured CAVI and divided the patients into two groups according to CAVI ≥8 (high CAVI, n = 164) or <8 (low CAVI, n = 44). ResultsCulprit plaques had significantly greater absolute NV (p = 0.016), %NV (p = 0.01), and smaller %FV (p = 0.02) in patients with high CAVI than in those with low CAVI. Patients with high CAVI had a higher prevalence of LNV plaques in culprit lesions than those with low CAVI (54% vs. 34%, p = 0.026). CAVI correlated significantly and positively with absolute NV, LV, and negatively with %FV. In logistic regression analysis after adjustment for the classic coronary risk factors and possible variables associated with vulnerable plaques, high CAVI had an independent and significant association with the presence of LNV plaques (OR, 3.37; 95% CI, 1.45–7.79; p = 0.0032). ConclusionsA high CAVI is associated with the composition of coronary culprit plaques, particularly increased amount of necrotic tissue, in patients with coronary artery disease undergoing PCI .

Total coronary atherosclerotic plaque burden is associated with myocardial ischemia in non-obstructive coronary artery disease.

AimWhether the total coronary atherosclerotic plaque burden is independently associated with myocardial ischemia in non-obstructive coronary artery disease (CAD) is not well established. We aimed to test the association of total plaque burden quantified by coronary computed tomography angiography (CCTA) with myocardial ischemia in patients with chronic coronary syndrome and non-obstructive CAD.MethodsWe included 125 patients (age 62 ± 9 years, 58% women) with chronic coronary syndrome and non-obstructive CAD (stenosis < 50%) by CCTA, who were grouped according to presence or absence of myocardial ischemia by myocardial contrast stress echocardiography. Total plaque burden was quantified by CCTA as the total plaque volume in the main coronary arteries, and positive remodelling was defined as remodelling index > 1.10.ResultsPatients with myocardial ischemia (n = 66) had higher total plaque burden (847 ± 245 mm3 vs. 758 ± 251 mm3, p = 0.049) and higher left ventricular (LV) mass index (42.1 ± 9.9 g/m2.7 vs. 37.3 ± 8.0 g/m2.7, p = 0.004), while age, sex, prevalence of hypertension, diabetes, calcium score and positive remodelling did not differ between the groups (all p > 0.05). In multivariable regression analysis, total plaque burden remained associated with presence of myocardial ischemia (OR 1.02, 95% CI 1.00–1.04, p = 0.045) independent of age, sex, hypertension, diabetes, LV mass index, coronary calcium score and positive remodelling.ConclusionTotal coronary artery plaque burden by CCTA was independently associated with myocardial ischemia in patients with non-obstructive CAD. Whether plaque quantification is useful for clinical management of patients with non-obstructive CAD should be tested in prospective studies.ClinicalTrials.gov: Identifier NCT01853527.

Relationship of Endothelial Shear Stress with Plaque Features with Coronary CT Angiography and Vasodilating Capability with PET.

Background Advances in three-dimensional reconstruction techniques and computational fluid dynamics of coronary CT angiography (CCTA) data sets make feasible evaluation of endothelial shear stress (ESS) in the vessel wall. Purpose To investigate the relationship between CCTA-derived computational fluid dynamics metrics, anatomic and morphologic characteristics of coronary lesions, and their comparative performance in predicting impaired coronary vasodilating capability assessed by using PET myocardial perfusion imaging (MPI). Materials and Methods In this retrospective study, conducted between October 2019 and September 2020, coronary vessels in patients with stable chest pain and with intermediate probability of coronary artery disease who underwent both CCTA and PET MPI with oxygen 15-labeled water or nitrogen 13 ammonia and quantification of myocardial blood flow were analyzed. CCTA images were used in assessing stenosis severity, lesion-specific total plaque volume (PV), noncalcified PV, calcified PV, and plaque phenotype. PET MPI was used in assessing significant coronary stenosis. The predictive performance of the CCTA-derived parameters was evaluated by using area under the receiver operating characteristic curve (AUC) analysis. Results There were 92 coronary vessels evaluated in 53 patients (mean age, 65 years ± 7; 31 men). ESS was higher in lesions with greater than 50% stenosis versus those without significant stenosis (mean, 15.1 Pa ± 30 vs 4.6 Pa ± 4 vs 3.3 Pa ± 3; P = .004). ESS was higher in functionally significant versus nonsignificant lesions (median, 7 Pa [interquartile range, 5-23 Pa] vs 2.6 Pa [interquartile range, 1.8-5 Pa], respectively; P ≤ .001). Adding ESS to stenosis severity improved prediction (change in AUC, 0.10; 95% CI: 0.04, 0.17; P = .002) for functionally significant lesions. Conclusion The combination of endothelial shear stress with coronary CT angiography (CCTA) stenosis severity improved prediction of an abnormal PET myocardial perfusion imaging result versus CCTA stenosis severity alone. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Kusmirek and Wieben in this issue.

Thoracic Aortic Calcification and Pre-Clinical Hypertension by New 2017 ACC/AHA Hypertension Guidelines.

The recently revised 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension (HTN) guidelines employ a lower blood pressure threshold to define HTN, aiming for earlier prevention of HTN-related cardiovascular diseases (CVD). Thoracic aortic calcification (TAC), a new surrogate marker of aging and aortic medial layer degeneration, and different stages of HTN, according to the 2017 ACC/AHA HTN guidelines, remain unknown. We classified 3022 consecutive asymptomatic individuals enrolled into four HTN categories using the revised 2017 ACC/AHA guidelines: normal blood pressure (NBP), elevated blood pressure (EBP), and stage 1 (S1) and stage 2 (S2) HTN. The coronary artery calcification score and TAC metrics (total Agaston TAC score, total plaque volume (mm3), and mean density (Hounsfield units, HU)) were measured using multi-detector computed tomography. Compared to NBP, a graded and significant increase in the TAC metrics was observed starting from EBP and S1 and S2 HTN, using the new 2017 ACC/AHA guidelines (NBP as reference; all trends: p < 0.001). These differences remained consistent after being fully adjusted. Older age (>50 years), S1 and S2 HTN, prevalent diabetes, and chronic kidney disease (<60 mL/min/1.73 m2) are all independently contributing factors to higher TAC risk using multivariate stepwise logistic regressions (all p ≤ 0.001). The optimal cutoff values of systolic blood pressure, diastolic blood pressure, and pulse pressure were 121, 74, and 45 mmHg, respectively, for the presence of TAC after excluding subjects with known CVD and ongoing HTN medication treatment. Our data showed that the presence of TAC starts at a stage of elevated blood pressure not categorized as HTN from the updated 2017 ACC/AHA hypertension guidelines.

Circumferential degree of carotid calcification is associated with new ischemic brain lesions after carotid artery stenting.

The relationship between plaque calcification and new ischemic brain lesions after carotid artery stenting (CAS) remains controversial. The purpose of this study was to determine if the circumferential degree of carotid calcification is associated with new ischemic brain lesions on diffusion-weighted imaging (DWI) after CAS. A total of 96 patients with carotid stenosis of ≥50% who underwent CAS were enrolled in the study. All patients underwent preoperative carotid computed tomography (CT), and preoperative and postoperative brain MRI. The brain MRI sequences included T1WI, T2WI, T2-fluid-attenuated inversion recovery (FLAIR), and DWI. The location, circumferential degree, volume, percentage volume, maximum density, mean density, Agatston score of carotid calcification, and total plaque volume were assessed and compared between patients with and without new ischemic brain lesions after CAS. Univariate and multivariate analyses were performed to evaluate predictors of new ischemic brain lesions. All of the 96 patients (67.8±6.8 years of age, 83.3% men) were included in the analysis. New ischemic brain lesions on DWI were observed in 40 patients (41.7%). Patients with new ischemic brain lesions after CAS had a larger circumferential degree of calcification than those without new ischemic brain lesions (P<0.001). There was only a possible trend toward significance for the percentage volume of calcification between the two groups with and without new brain ischemic lesions (P=0.07). No significant differences were found regarding the location (P=0.18), volume (P=0.37), maximum density (P=0.44), mean density (P=0.39), Agatston score (P=0.28), and total plaque volume (P=0.33) of carotid calcification between the DWI+ and DWI- groups. In the multivariate analysis, an increased risk of new ischemic brain lesions was observed in patients with a high score for the circumferential degree of calcification [score 3; odds ratio (OR): 10.7, P<0.001; score 4, OR: 11.7, P=0.038]. The circumferential degree of carotid calcification was associated with new ischemic brain lesions after CAS. CAS should be avoided if possible for carotid stenosis with large circumferential calcified plaques.

Prognostic Implications of Comprehensive Whole Vessel Plaque Quantification Using Coronary Computed Tomography Angiography.

The prognostic value of whole vessel plaque quantification has not been fully understood. We aimed to investigate the clinical relevance of whole vessel plaque quantification on coronary computed tomography angiography. In a total of 1,013 vessels with fractional flow reserve (FFR) measurement and available coronary computed tomography angiography, high-risk plaque characteristics (HRPC) included minimum lumen area<4mm2, plaque burden≥70%, low attenuation plaque, positive remodeling, spotty calcification, and napkin-ring sign; and high-risk vessel characteristics (HRVC) included total plaque volume≥306.5 mm3, fibrofatty and necrotic core volume≥4.46 mm3, or percent total atheroma volume≥32.2% in a target vessel, based on corresponding optimal cutoff values. Survival analysis for vessel-oriented composite outcome (VOCO) (a composite of cardiac death, target vessel myocardial infarction, or target vessel revascularization) at 5 years was performed using marginal Cox proportional hazard models. Whole vessel plaque quantification had incremental predictability in addition to % diameter stenosis and HRPC (P< 0.001) in predicting FFR≤0.80. Among 517 deferred vessels based on FFR >0.80, the number of HRVC was significantly associated with the risk of VOCO (HR: 2.54; 95%CI: 1.77-3.64) and enhanced the predictability for VOCO of % diameter stenosis and the number of HRPC (P< 0.001). In a landmark analysis at 2 years, the number of HRVC showed sustained prognostic implications beyond 2 years, but the number of HRPC did not. Whole vessel plaque quantification can provide incremental predictability for low FFR and additive prognostic value in deferred vessels with high FFR over anatomical severity and lesion plaque characteristics. (CCTA-FFR Registry for Risk Prediction; NCT04037163).

High-Risk Morphological and Physiological Coronary Disease Attributes as Outcome Markers After Medical Treatment and Revascularization

ObjectivesThis study sought to evaluate the prognostic impact of plaque morphology and coronary physiology on outcomes after medical treatment or percutaneous coronary intervention (PCI). BackgroundAlthough fractional flow reserve (FFR) is currently best practice, morphological characteristics of coronary artery disease also contribute to outcomes. MethodsA total of 872 vessels in 538 patients were evaluated by invasive FFR and coronary computed tomography angiography. High-risk attributes (HRA) were defined as high-risk physiological attribute (invasive FFR ≤0.8) and high-risk morphological attributes including: 1) local plaque burden (minimum lumen area <4 mm2 and plaque burden ≥70%); 2) adverse plaque characteristics ≥2; and 3) global plaque burden (total plaque volume ≥306.5 mm3 and percent atheroma volume ≥32.2%). The primary outcome was the composite of revascularization, myocardial infarction, or cardiac death at 5 years. ResultsThe mean FFR was 0.88 ± 0.08, and PCI was performed in 239 vessels. The primary outcome occurred in 54 vessels (6.2%). All high-risk morphological attributes were associated with the increased risk of adverse outcomes after adjustment for FFR ≤0.8 and demonstrated direct prognostic effect not mediated by FFR ≤0.8. The 5-year event risk proportionally increased as the number of HRA increased (p for trend <0.001) with lower risk in the PCI group than the medical treatment group in vessels with 1 or 2 HRA (9.7% vs. 14.7%), but not in vessels with either 0 or ≥3 HRA. Of the vessels with pre-procedural FFR ≤0.8, ischemia relief by PCI (pre-PCI FFR ≤0.8 and post-PCI FFR >0.8) significantly reduced vessel-oriented composite outcome risk compared with medical treatment alone in vessels with 0 or 1 high-risk morphological attributes (hazard ratio: 0.33; 95% confidence interval: 0.12 to 0.93; p = 0.035), but the risk reduction was attenuated in vessels with ≥2 high-risk morphological attributes. ConclusionsHigh-risk morphological attributes offered additive prognostic value to coronary physiology and may optimize selection of treatment strategies by adding to FFR-based risk predictions (CCTA-FFR Registry for Development of Comprehensive Risk Prediction Model; NCT04037163)

Association of Coronary Artery Atherosclerosis With Brain White Matter Hyperintensity.

We aim to determine, in healthy high-risk adults, the association between subclinical coronary artery disease and white matter hyperintensity (WMH) volume and location, independent of atherosclerotic risk factors. Seven hundred eighty-two asymptomatic first-degree relatives of index cases with early-onset coronary artery disease (<60 years old) from GeneSTAR (Genetic Study of Atherosclerosis Risk) with contemporaneous coronary computed tomography angiography and brain magnetic resonance imaging were analyzed. Multilevel mixed-effects linear regression models, accounting for family structure, evaluated the association of total WMH volume and 3 regions (deep WMH, periventricular WMH [PVWMH], or borderzone [cuff]) with markers of coronary artery disease. Separate models were created for total WMH, deep WMH, PVWMH, and cuff volumes, each, as dependent variables, across coronary computed tomography angiography variables, adjusted for covariates. Mean age was 51 years ±10, with 58% women and 39% African American people. Participants with any coronary plaque had 52% larger WMH volumes than those without plaque (95% CI, 0.24–0.59). Per 1% greater coronary plaque volume, total WMH volumes were 0.07% larger (95% CI, 0.04–0.10). Every 1% higher total coronary plaque volume was associated with 5.03% larger deep WMH volume (95% CI, 4.67–5.38), 5.10% PVWMH larger volume (95% CI, 4.72–5.48), and 2.74% larger cuff volume (95% CI, 2.38–3.09) with differences in this association when comparing deep WMH to PVWMH (P interaction, 0.001) or cuff (P interaction, <0.001), respectively. In healthy, high-risk individuals, the presence and volume of coronary artery plaque are associated with larger WMH volumes, appearing the strongest for PVWMH. These findings in high-risk families suggest a disease relationship in 2 different vascular beds, beyond traditional risk factors, possibly due to genetic predisposition.

Prognostic Value of RCA Pericoronary Adipose Tissue CT-Attenuation Beyond High-Risk Plaques, Plaque Volume, and Ischemia

ObjectivesThis study was designed to assess the prognostic value of pericoronary adipose tissue computed tomography attenuation (PCATa) beyond quantitative coronary computed tomography angiography (CCTA)–derived plaque volume and positron emission tomography (PET) determined ischemia. BackgroundInflammation plays a crucial role in atherosclerosis. PCATa has been shown to assess coronary-specific inflammation and is of prognostic value in patients with suspected coronary artery disease (CAD). MethodsA total of 539 patients who underwent CCTA and [15O]H2O PET perfusion imaging because of suspected CAD were included. Imaging assessment included coronary artery calcium score (CACS), presence of obstructive CAD (≥50% stenosis) and high-risk plaques (HRPs), total plaque volume (TPV), calcified/noncalcified plaque volume (CPV/NCPV), PCATa, and myocardial ischemia. The endpoint was a composite of death and nonfatal myocardial infarction. Prognostic thresholds were determined for quantitative CCTA variables. ResultsDuring a median follow-up of 5.0 (interquartile range: 4.7 to 5.0) years, 33 events occurred. CACS >59 Agatston units, obstructive CAD, HRPs, TPV >220 mm3, CPV >110 mm3, NCPV >85 mm3, and myocardial ischemia were associated with shorter time to the endpoint with unadjusted hazard ratios (HRs) of 4.17 (95% confidence interval [CI]: 1.80 to 9.64), 4.88 (95% CI: 1.88 to 12.65), 3.41 (95% CI: 1.72 to 6.75), 7.91 (95% CI: 3.05 to 20.49), 5.82 (95% CI: 2.40 to 14.10), 8.07 (95% CI: 3.33 to 19.55), and 4.25 (95% CI: 1.84 to 9.78), respectively (p < 0.05 for all). Right coronary artery (RCA) PCATa above scanner specific thresholds was associated with worse prognosis (unadjusted HR: 2.84; 95% CI: 1.44 to 5.63; p = 0.003), whereas left anterior descending artery and circumflex artery PCATa were not related to outcome. RCA PCATa above scanner specific thresholds retained is prognostic value adjusted for imaging variables and clinical characteristics associated with the endpoint (adjusted HR: 2.45; 95% CI: 1.23 to 4.93; p = 0.011). ConclusionsParameters associated with atherosclerotic burden and ischemia were more strongly associated with outcome than RCA PCATa. Nonetheless, RCA PCATa was of prognostic value beyond clinical characteristics, CACS, obstructive CAD, HRPs, TPV, CPV, NCPV, and ischemia.

Marked plaque regression in homozygous familial hypercholesterolemia

Background and aimsBoth plasma low-density lipoprotein (LDL) cholesterol levels and risk for premature cardiovascular disease are extremely elevated in patients with homozygous familial hypercholesterolemia (HoFH), despite the use of multiple cholesterol lowering treatments. Given its inborn nature, atherosclerotic plaques are commonly observed in young HoFH patients. Whether intensive lipid lowering strategies result in plaque regression in adolescent patients is unknown. MethodsTwo HoFH patients with null/null LDLR variants, who participated in the R1500-CL-1629 randomized clinical trial (NCT03399786) evaluating the LDL cholesterol lowering effect of evinacumab (a human antibody directed against ANGPTL3; 15 mg/kg intravenously once monthly), were included in this study. Patients underwent coronary computed tomography angiography (CCTA) before randomization and after 6 months of treatment. ResultsBoth patient A (aged 12) and B (aged 16) were treated with a statin, ezetimibe and weekly apheresis. Evinacumab decreased mean pre-apheresis LDL cholesterol levels from 5.51 ± 0.75 and 5.07 ± 1.45 mmol/l to 2.48 ± 0.31 and 2.20 ± 0.13 mmol/l and post-apheresis LDL levels from 1.45 ± 0.26 and 1.37 ± 39 mmol/l to 0.80 ± 0.16 and 0.78 ± 0.13 mmol/l in patient A and B, respectively. Total plaque volumes were reduced by 76% and 85% after 6 months of evinacumab treatment in patient A and B, respectively. ConclusionsWe describe two severely affected young HoFH patients in whom profound plaque reduction was observed with CCTA after intensive lipid lowering therapy with statins, ezetimibe, LDL apheresis, and evinacumab. This shows that atherosclerotic plaques possess the ability to regress at young age, even in HoFH patients.

Three-dimensional ultrasound imaging: An effective method to detect the effect of moderate intensity statin treatment in slowing carotid plaque progression.

We aimed to evaluate the feasibility of three-dimensional ultrasound imaging (3DUS) in assessing the therapeutic effect of moderate-intensity statin therapy on carotid atherosclerotic plaques. Patients with carotid plaques were recruited to the study from January 2016 to September 2018, and were divided into two groups based on whether or not they were taking statins. All participants underwent 3DUS of their carotid plaques at baseline, then 3months and 2 years after initial examination. The changes of the carotid plaques were compared between the two groups. Were included 97 patients (57 males and 40 females), 65.26 ± 9.53 year-old with 67 into the statin group and 30 in the control group. The baseline levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were lower in the statin group than in the control group (3.79 ± 0.78 mmol/L vs 4.50 ± 1.12 mmol/L; 2.01 ± 0.62 mmol/L vs 2.58 ± 0.91 mmol/L, P< .05). There was no significant difference in the change of total plaque volume (TPV) detected by 3D-US between the statin (median [interquartile range]: 0 [-30-20] mm3 ) and the control group (0 [-22.5-25] mm3 ) at 3months. Over 2 years, the TPV increased faster in the control group (+70 [25-150] mm3 ), than in the statin group (15 [-57.5-90) mm3 , P< .05). 3DUS can be an effective tool to observe the development of carotid plaques and the effect of statin treatment.

Three-dimensional ultrasound for carotid vessel wall volume measurement.

Objectives:The intima–media thickness (IMT) of the carotid artery can now be detected on a three-dimensional (3D) plane. The 3D vessel wall volume (VWV) more accurately represents vascular conditions. Through 3D ultrasound, we established a standardized method for carotid VWV measurement.Materials and Methods:A total of thirty patients without stroke or cardiovascular disease who received carotid duplex sonography were retrospectively reviewed. Gray-scale 3D images from the distal common carotid artery (CCA) to internal carotid artery on both sides were acquired using a single-sweep 3D transducer and analyzed offline by using the vascular plaque quantification function of the Philips QLAB software. Then, the 3D IMT(QLAB intima–media thickness [QIMT]), total plaque volume (TPV), and VWV were measured by a neurologist and a technician, and the interobserver variability was assessed.Results:The mean two-dimensional (2D) carotid IMT was 0.65 ± 0.12 mm. The mean QIMT, TPV, and VWV measured by observer 1 were 0.68 ± 0.18 mm, 26 ± 12 mm3, and 94 ± 10 mm3, respectively. The Bland–Altman plot of the mean differences between the QIMT, TPV, and VWV values measured by observers 1 and 2 showed that those of observer 2 were within two standard deviations of those of observer 1. Intraclass correlation coefficients (ICCs) indicated strong correlations in QIMT (ICC = 0.76), TPV (ICC = 0.85), and VWV (ICC = 0.90; P < 0.001) between observers 1 and 2. Both 2D IMT and 3D QIMT exhibited a positive linear correlation with age.Conclusion:This study established a standardized VWV measurement through 3D ultrasound. Reasonable interobserver differences were obtained within a 95% limit of agreement and high reliability (ICC = 0.90). The VWV 1 cm from the CCA bifurcation was quantified with a mean value of 94.2 mm3. Further studies on the 3D ultrasound quantification of carotid arteries are warranted.

Effects of chronic kidney disease and declining renal function on coronary atherosclerotic plaque progression: a PARADIGM substudy

To investigate the change in atherosclerotic plaque volume in patients with chronic kidney disease (CKD) and declining renal function, using coronary computed tomography angiography (CCTA). In total, 891 participants with analysable serial CCTA and available glomerular filtration rate (GFR, derived using Cockcroft-Gault formulae) at baseline (CCTA 1) and follow-up (CCTA 2) were included. CKD was defined as GFR <60 mL/min/1.73 m2. Declining renal function was defined as ≥10% drop in GFR from the baseline. Quantitative assessment of plaque volume and composition were performed on both scans. There were 203 participants with CKD and 688 without CKD. CKD was associated with higher baseline total plaque volume, but similar plaque progression, measured by crude (57.5 ± 3.4 vs. 65.9 ± 7.7 mm3/year, P = 0.28) or annualized (17.3 ± 1.0 vs. 19.9 ± 2.0 mm3/year, P = 0.25) change in total plaque volume. There were 709 participants with stable GFR and 182 with declining GFR. Declining renal function was independently associated with plaque progression, with higher crude (54.1 ± 3.2 vs. 80.2 ± 9.0 mm3/year, P < 0.01) or annualized (16.4 ± 0.9 vs. 23.9 ± 2.6 mm3/year, P < 0.01) increase in total plaque volume. In CKD, plaque progression was driven by calcified plaques whereas in patients with declining renal function, it was driven by non-calcified plaques. Decline in renal function was associated with more rapid plaque progression, whereas the presence of CKD was not.

Sex differences in coronary plaque changes assessed by serial computed tomography angiography

Long-term data on sex-differences in coronary plaque changes over time is lacking in a low-to-intermediate risk population of stable coronary artery disease (CAD). The aim of this study was to evaluate the role of sex on long-term plaque progression and evolution of plaque composition. Furthermore, the influence of menopause on plaque progression and composition was also evaluated. Patients that underwent a coronary computed tomography angiography (CTA) were prospectively included to undergo a follow-up coronary CTA. Total and compositional plaque volumes were normalized using the vessel volume to calculate a percentage atheroma volume (PAV). To investigate the influence of menopause on plaque progression, patients were divided into two groups, under and over 55 years of age. In total, 211 patients were included in this analysis, 146 (69%) men. The mean interscan period between baseline and follow-up coronary CTA was 6.2 ± 1.4 years. Women were older, had higher HDL levels and presented more often with atypical chest pain. Men had 434 plaque sites and women 156. On a per-lesion analysis, women had less fibro-fatty PAV compared to men (β -1.3 ± 0.4%; p < 0.001), with no other significant differences. When stratifying patients by 55 years age threshold, fibro-fatty PAV remained higher in men in both age groups (p < 0.05) whilst women younger than 55 years demonstrated more regression of fibrous (β -0.8 ± 0.3% per year; p = 0.002) and non-calcified PAV (β -0.7 ± 0.3% per year; p = 0.027). In a low-to-intermediate risk population of stable CAD patients, no significant sex differences in total PAV increase over time were observed. Fibro-fatty PAV was lower in women at any age and women under 55 years demonstrated significantly greater reduction in fibrous and non-calcified PAV over time compared to age-matched men. (ClinicalTrials.gov number, NCT04448691.)

Circulating β-d-Glucan as a Marker of Subclinical Coronary Plaque in Antiretroviral Therapy-Treated People With Human Immunodeficiency Virus.

BackgroundDespite antiretroviral therapy (ART), people with human immunodeficiency virus (PWH) have increased risk of inflammatory comorbidities, including cardiovascular diseases. Gut epithelial damage, and translocation of bacterial lipopolysaccharide (LPS) or fungal β-d-glucan (BDG) drive inflammation in ART-treated PWH. In this study, we investigated whether markers of gut damage and microbial translocation were associated with cardiovascular risk in asymptomatic ART-treated PWH.MethodsWe cross-sectionally analyzed plasma from 93 ART-treated PWH and 52 uninfected controls older than 40 years of age from the Canadian HIV and Aging Cohort. Participants were cardiovascular disease free and underwent a cardiac computed tomography (CT) to measure total coronary atherosclerotic plaque volume (TPV). Levels of bacterial LPS and gut damage markers REG3α and I-FABP were measured by enzyme-linked immunosorbent assay. Fungal BDG levels were analyzed using the Fungitell assay.Resultsβ-d-glucan levels but not LPS were significantly elevated in ART-treated PWH with coronary artery plaque (P = .0007). Moreover, BDG but not LPS levels correlated with TPV (r = 0.26, P = .01). Intestinal fatty acid binding protein (I-FABP) but not REG3α levels correlated with TPV (r = 0.23, P = .03). However, BDG and LPS levels were not elevated in uninfected controls with plaque. In multivariable models, elevated BDG levels were independently associated with the presence of coronary atherosclerosis in PWH but not in uninfected controls.ConclusionsTranslocation of fungal BDG was associated with coronary atherosclerosis assessed by CT-scan imaging in ART-treated PWH, suggesting a human immunodeficiency virus-specific pathway leading to cardiovascular disease. Further investigation is needed to appraise causality of this association. Translocation of fungal products may represent a therapeutic target to prevent cardiovascular disease in ART-treated PWH.Plasma levels of the fungal product β-D-Glucan, but not the bacterial product lipopolysaccharide, are associated with the presence and the size of subclinical coronary atherosclerosis plaque in people living with HIV taking antiretroviral therapy, independently of classical cardiovascular risk factors.

Abstract P372: Sex-Differences in Carotid Plaque Composition in Patients With Embolic Stroke of Undetermined Source

Introduction: Non-stenotic carotid plaque may be the cause of ischemic stroke in some patients with embolic stroke of undetermined source (ESUS). We examined sex-differences in carotid plaque composition in patients with ESUS. Methods: A retrospective cohort of anterior circulation acute ischemic stroke patients with CTA head/neck and meeting criteria for ESUS was identified. Carotid artery bifurcations (4cm segment) ipsilateral to the stroke were evaluated using a semi-automated segmentation software to measure total plaque volume and plaque subcomponents (calcium, intraplaque hemorrhage [IPH], and lipid rich necrotic core [LRNC]). Sex-differences in baseline vascular risk factors and plaque subcomponent volumes were tested by Mann-Whitney U tests or students t-tests for continuous variables and Fisher’s exact test for categorical variables. Associations of each plaque subcomponent were tested by multivariate linear regressions. Results: Of 94 patients, 55% were women. Mean age of the cohort was 65 years. Women had higher body mass indices than men (29.2 vs 26.3; p=0.02). There were no other significant differences in age or vascular risk factors between men and women. Overall plaque volume (p=0.001) was significantly greater in men as was the volume of calcification (p&lt;0.001) and IPH (p=0.008) in carotid arteries ipsilateral to the stroke (Figure). No significant difference was detected in LRNC volume by sex (p=0.84). In multivariate analysis, male sex (β=45.9, 95% CI 18.0-73.7, p=0.002) and older age (β=1.85, 95% CI 0.73-3.0, p=0.001) were significantly associated with calcified plaque volume, and male sex (β= 6.7, 95% CI 2.6-10.8, p=0.002) with IPH. Neither age nor sex was significantly associated with LRNC. Conclusions: Sex-differences in carotid plaque composition in ESUS suggest the possibility of a differential contribution of non-stenotic carotid plaque to stroke mechanism in men versus women.

Management of Cardiovascular Disease in Kidney Disease Study: Rationale and Design

Introduction: Atherosclerosis, inflammation, and vascular stiffness are prominent interrelated risk factors contributing to the high incidence of cardiovascular disease (CVD) in patients with CKD. Conventional CVD management strategies in CKD largely target atherosclerotic CVD and have had a limited impact on the cardiovascular mortality in this population. Multiple in vivo and in vitro studies and epidemiological evidence from the rheumatologic cohorts have shown that low-dose hydroxychloroquine has beneficial effects on inflammation, endothelial function, insulin sensitivity, and metabolic syndrome. Our recent proof-of-concept animal study showed that hydroxychloroquine has marked protection against atherosclerosis and vascular stiffness. We hypothesize that hydroxychloroquine has the potential to provide significant cardiovascular benefits in patients with CKD. Methods: The Management of Cardiovascular disease in Kidney disease study (NCT 03636152) is a phase 2B, randomized, double-blind, placebo-controlled trial evaluating the effects of low-dose hydroxychloroquine therapy on the parameters of atherosclerosis, inflammation, and vascular stiffness in patients with CKD. The study plans to enroll 100 CKD patients estimated to be at high cardiovascular risk by a combination of low estimated glomerular filtration rate and albuminuria and treat them for 18 months with hydroxychloroquine or placebo in 1:1 allocation. Results: The study will assess the change in the total carotid plaque volume as measured by serial noncontrast carotid MRI as the primary outcome and the serial changes in plasma inflammation markers, vascular stiffness, renal function, and the composition characteristics of the carotid plaque as secondary outcome measures. Discussion/Conclusion: The results of this trial will provide the proof-of-applicability for hydroxychloroquine in the CVD in CKD. If positive, this trial should lead to phase-3 trials with clinical end points for this potentially transformative, novel, and inexpensive therapy for CVD in CKD.

Contribution of Risk Factors to the Development of Coronary Atherosclerosis as Confirmed via Coronary CT Angiography: A Longitudinal Radiomics-based Study.

Background Various cardiovascular risk factors are thought to modify atherosclerosis in a similar fashion (ie, by increasing the magnitude of coronary artery disease [CAD]). However, coronary CT angiography allows precision phenotyping of plaque characteristics through use of radiomics. Purpose To assess whether different cardiovascular risk factors have distinctive contributions to the changes in plaque morphologic features over time. Materials and Methods Individuals with or without HIV infection and cocaine use and without cardiovascular symptoms underwent coronary CT angiography between May 2004 and August 2015. In the current HIPAA-compliant study, the effects of cocaine use, HIV infection, and atherosclerotic cardiovascular disease (ASCVD) risk on the temporal changes (mean ± standard deviation, 4.0 years ± 2.3 between CT angiographic examinations) in CAD structure were analyzed by using radiomic analysis. The changes in radiomic features were analyzed by using linear mixed models, with correction for factors that may change plaque structure: high-sensitivity C-reactive protein level, statin use, positive family history of CAD, and total plaque volume to account for any potential intrinsic correlation between volume and morphologic features. Clusters among significant radiomic features were identified by using hierarchical clustering. Bonferroni-corrected P values less than .00004 (.05 divided by 1276) were considered to indicate significant differences. Results Of 1429 participants, 300 with CAD confirmed at coronary CT angiography were randomly selected (mean age, 48 years ± 7; 210 men, 226 people infected with HIV, 174 people who use cocaine) and 1276 radiomic features were quantified for each plaque. Cocaine use was significantly associated with 23.7% (303 of 1276) of the radiomic features, HIV infection was significantly associated with 1.3% (17 of 1276), and elevated ASCVD risk was significantly associated with 8.2% (104 of 1276) (P < .00004 for all). Parameters associated with elevated ASCVD risk or cocaine use and HIV infection did not overlap. There were 13 clusters among the 409 parameters, eight of which were affected only by cocaine use and three of which were affected only by ASCVD risk. Conclusion Radiomics-based precision phenotyping indicated that conventional risk factors, cocaine use, and HIV infection each had different effects on CT angiographic morphologic changes in coronary atherosclerosis over 4 years. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Schoepf and Emrich in this issue.

Pericoronary adipose tissue attenuation leads to improved prognostication beyond atherosclerotic burden and high-risk plaques in patients with suspected coronary artery disease

Abstract Funding Acknowledgements Type of funding sources: None. Background Inflammation is a key component in the atherosclerotic process, initiating and sustaining plaques and serving as a trigger for plaque rupture leading to myocardial infarction. Coronary computed tomography angiography (CCTA) derived pericoronary adipose tissue attenuation (PCATa) has been proposed as surrogate marker for coronary inflammation and might improve risk assessment on top of CCTA derived cardiovascular risk-factors: atherosclerotic burden and plaque vulnerability. Purpose To assess the prognostic value of PCATa beyond atherosclerotic burden and high-risk plaques (HRPs). Methods A total of 543 patients who underwent CCTA because of suspected CAD were included. CCTA assessment comprised coronary artery calcium score (CACS), presence of obstructive CAD (≥50% stenosis) and HRPs, total plaque volume (TPV), non-calcified plaque volume (NCPV), and PCATa. The endpoint was a composite of death and non-fatal myocardial infarction (MI). Prognostic thresholds were determined for quantitative CCTA variables. Results During a median follow-up of 6.6 [interquartile range: 4.7-7.8] years, the endpoint was observed in 42 (20 MI/22 death) patients. CACS &amp;gt;83, obstructive CAD, HRPs, TPV &amp;gt;269mm3, and NCPV &amp;gt;83mm3 were associated with shorter time to the endpoint with unadujsted hazard ratio’s (HR) of 5.37 (95% confidence interval (CI): 2.56-11.29), 5.70 (95% CI: 2.40-13.55), 3.31 (95% CI: 1.80-6.07), 7.76 (95% CI: 3.59-16.81), and 6.77 (95% CI: 3.24-14.16), respectively (p &amp;lt; 0.001 for all). PCATa of the RCA &amp;gt;-74.4 Hounsfield units was associated with worse prognosis (unadjusted HR: 1.99, 95% CI: 1.04-3.79, p = 0.037), whereas PCATa of the LAD and Cx were not associated with prognosis. PCATa of the RCA remained a significant predictor of death and non-fatal MI corrected for CCTA variables and clincal chacteristics associated with the endpoint (adjusted HR: 2.11, 95% CI: 1.11-4.04, p = 0.024). Conclusion Coronary inflammation determined by PCATa of the RCA provides incremental prognostic value beyond clinical characteristics and comprehensive CCTA assessment. Abstract Figure. Take-home figure

CCTA-derived functional and morphological features and their comparative performance in predicting impaired coronary vasodilatation by PET-myocardial perfusion imaging

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This work was supported in part from European Regional Development Fund, Operational Programme “Competitiveness, Entrepreneurship and Innovation 2014-2020 (EPAnEK)”, titled: The Greek Research Infrastructure for Personalized Medicine (pMED-GR) , no. GR 5002802 ,and by Greece and the European Union (European Social Fund-ESF) through the Operational Programme «Human Resources Development, Education and Lifelong Learning 2014-2020» in the context of the project “Assessment of coronary atherosclerosis: a new complete, anatomo-functional, morphological and biomechanical approach”, Project no. 504776 onbehalf EVINCI-SMARTOOL Background/Objectives: The relationship between biomechanical characteristics of a coronary lesion with myocardial blood flow has not been studied. We investigated the relationship between local endothelial shear stress (ESS) and computed tomography coronary angiography (CTCA)-derived anatomical and plaque characteristics data with impaired vasodilating capability assessed by positron emission tomography myocardial perfusion imaging (PET-MPI). Methods A total of 92 coronary vessels of 53 patients who have undergone both CTCA and PET-MPI with 15O-water or 13N-ammonia were analysed. PET was considered abnormal when &amp;gt; 1 contiguous segments showed both stress Myocardial Blood Flow (MBF) ≤2.3mL/g/min and Myocardial Flow Reserve (MFR) ≤2.5 for 15O-water or &amp;lt;1.79 mL/g/min and ≤2.0 for 13N-ammonia respectively. CTCA images were used to assess stenosis severity, lesion specific total plaque volume (PV), non-calcified PV and calcified PV as well as plaque phenotype. ESS was calculated for the full length of a lesion (total), as well as in the proximal, minimum lumen area and distal lesion segments. Results ESS was weakly correlated with total PV (rho = 0.273, p = 0.008), non-calcified PV (rho = 0.247, p = 0.017) and the volume of necrotic core (rho = 0.242, p = 0.02). ESS increased progressively with stenosis severity (p ≤ 0.001). ΕSS was also higher in functionally significant vs. non-significant lesions (10.4 [8.04-54.4] Pa vs. 3.9 [2.32-7.29] Pa, p ≤0.001). Addition of ESS to stenosis severity improved prediction (Δ[AUC]:0.113, 95% CI: 0.055 to 0.171, p = 0.0001) of functionally significant lesions. Conclusion There is a weak positive association between lesion-specific ESS and plaque volume. ESS increases progressively with stenosis severity and is higher in functionally significant lesions by PET-MPI. The addition of ESS to CTCA-anatomical information improves prediction of an abnormal PET-MPI result.