Background and aimsInhibition of Renin-Angiotensin-Aldosterone-System (RAAS) has been hypothesized to improve endothelial function and reduce plaque inflammation, however, their impact on the... Show moreBackground and aimsInhibition of Renin-Angiotensin-Aldosterone-System (RAAS) has been hypothesized to improve endothelial function and reduce plaque inflammation, however, their impact on the progression of coronary atherosclerosis is unclear. We aim to study the effects of RAAS inhibitor on plaque progression and composition assessed by serial coronary CT angiography (CCTA).MethodsWe performed a prospective, multinational study consisting of a registry of patients without history of CAD, who underwent serial CCTAs. Patients using RAAS inhibitors were propensity matched to RAAS inhibitor naïve patients based on clinical and CCTA characteristics at baseline. Atherosclerotic plaques in CCTAs were quantitatively analyzed for percent atheroma volume (PAV) according to plaque composition. Interactions between RAAS inhibitor use and baseline PAV on plaque progression were assessed in the unmatched cohort using a multivariate linear regression model.ResultsOf 1248 patients from the registry, 299 RAAS inhibitor taking patients were matched to 299 RAAS inhibitor naïve patients. Over a mean interval of 3.9 years, there was no significant difference in annual progression of total PAV between RAAS inhibitor naïve vs taking patients (0.75 vs 0.79%/year, p = 0.66). With interaction testing in the unmatched cohort, however, RAAS inhibitor use was significantly associated with lower non-calcified plaque progression (Beta coefficient −0.100, adjusted p = 0.038) with higher levels of baseline PAV.ConclusionsThe use of RAAS inhibitors over a period of nearly 4 years did not significantly impact on total atherosclerotic plaque progression or various plaque components. However, interaction testing to assess the differential effect of RAAS inhibition based on baseline PAV suggested a significant decrease in progression of non-calcified plaque in patients with a higher burden of baseline atherosclerosis, which should be considered hypothesis generating. Show less
AimsTo investigate the impact of statins on plaque progression according to high-risk coronary atherosclerotic plaque (HRP) features and to identify predictive factors for rapid plaque progression... Show moreAimsTo investigate the impact of statins on plaque progression according to high-risk coronary atherosclerotic plaque (HRP) features and to identify predictive factors for rapid plaque progression in mild coronary artery disease (CAD) using serial coronary computed tomography angiography (CCTA).Methods and resultsWe analyzed mild stenosis (25–49%) CAD, totaling 1432 lesions from 613 patients (mean age, 62.2 years, 63.9% male) and who underwent serial CCTA at a ≥2 year inter-scan interval using the Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging (NCT02803411) registry. The median inter-scan period was 3.5 ± 1.4 years; plaques were quantitatively assessed for annualized percent atheroma volume (PAV) and compositional plaque volume changes according to HRP features, and the rapid plaque progression was defined by the ≥90th percentile annual PAV. In mild stenotic lesions with ≥2 HRPs, statin therapy showed a 37% reduction in annual PAV (0.97 ± 2.02 vs. 1.55 ± 2.22, P = 0.038) with decreased necrotic core volume and increased dense calcium volume compared to non-statin recipient mild lesions. The key factors for rapid plaque progression were ≥2 HRPs [hazard ratio (HR), 1.89; 95% confidence interval (CI), 1.02–3.49; P = 0.042], current smoking (HR, 1.69; 95% CI 1.09–2.57; P = 0.017), and diabetes (HR, 1.55; 95% CI, 1.07–2.22; P = 0.020).ConclusionIn mild CAD, statin treatment reduced plaque progression, particularly in lesions with a higher number of HRP features, which was also a strong predictor of rapid plaque progression. Therefore, aggressive statin therapy might be needed even in mild CAD with higher HRPs. Show less
BackgroundStatins reduce the incidence of major cardiovascular events, but residual risk remains. The study examined the determinants of atherosclerotic statin nonresponse.ObjectivesThis study... Show moreBackgroundStatins reduce the incidence of major cardiovascular events, but residual risk remains. The study examined the determinants of atherosclerotic statin nonresponse.ObjectivesThis study aimed to investigate factors associated with statin nonresponse-defined atherosclerosis progression in patients treated with statins.MethodsThe multicenter PARADIGM (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging) registry included patients who underwent serial coronary computed tomography angiography ≥2 years apart, with whole-heart coronary tree quantification of vessel, lumen, and plaque, and matching of baseline and follow-up coronary segments and lesions. Patients with statin use at baseline and follow-up coronary computed tomography angiography were included. Atherosclerotic statin nonresponse was defined as an absolute increase in percent atheroma volume (PAV) of 1.0% or more per year. Furthermore, a secondary endpoint was defined by the additional requirement of progression of low-attenuation plaque or fibro-fatty plaque.ResultsThe authors included 649 patients (age 62.0 ± 9.0 years, 63.5% male) on statin therapy and 205 (31.5%) experienced atherosclerotic statin nonresponse. Age, diabetes, hypertension, and all atherosclerotic plaque features measured at baseline scan (high-risk plaque [HRP] features, calcified and noncalcified PAV, and lumen volume) were significantly different between patients with and without atherosclerotic statin nonresponse, whereas only diabetes, number of HRP features, and noncalcified and calcified PAV were independently associated with atherosclerotic statin nonresponse (odds ratio [OR]: 1.41 [95% CI: 0.95-2.11], OR: 1.15 [95% CI: 1.09-1.21], OR: 1.06 [95% CI: 1.02-1.10], OR: 1.07 [95% CI: 1.03-1.12], respectively). For the secondary endpoint (N = 125, 19.2%), only noncalcified PAV and number of HRP features were the independent determinants (OR: 1.08 [95% CI: 1.03-1.13] and OR: 1.21 [95% CI: 1.06-1.21], respectively).ConclusionsIn patients treated with statins, baseline plaque characterization by plaque burden and HRP is associated with atherosclerotic statin nonresponse. Patients with the highest plaque burden including HRP were at highest risk for plaque progression, despite statin therapy. These patients may need additional therapies for further risk reduction. Show less
Park, H.B.; Lee, J.; Hong, Y.; Byungchang, S.; Kim, W.; Lee, B.K.; ... ; Chang, H.J. 2023
Background and HypothesisThe recently introduced Bayesian quantile regression (BQR) machine-learning method enables comprehensive analyzing the relationship among complex clinical variables. We... Show moreBackground and HypothesisThe recently introduced Bayesian quantile regression (BQR) machine-learning method enables comprehensive analyzing the relationship among complex clinical variables. We analyzed the relationship between multiple cardiovascular (CV) risk factors and different stages of coronary artery disease (CAD) using the BQR model in a vessel-specific manner.MethodsFrom the data of 1,463 patients obtained from the PARADIGM (NCT02803411) registry, we analyzed the lumen diameter stenosis (DS) of the three vessels: left anterior descending (LAD), left circumflex (LCx), and right coronary artery (RCA). Two models for predicting DS and DS changes were developed. Baseline CV risk factors, symptoms, and laboratory test results were used as the inputs. The conditional 10%, 25%, 50%, 75%, and 90% quantile functions of the maximum DS and DS change of the three vessels were estimated using the BQR model.ResultsThe 90th percentiles of the DS of the three vessels and their maximum DS change were 41%–50% and 5.6%–7.3%, respectively. Typical anginal symptoms were associated with the highest quantile (90%) of DS in the LAD; diabetes with higher quantiles (75% and 90%) of DS in the LCx; dyslipidemia with the highest quantile (90%) of DS in the RCA; and shortness of breath showed some association with the LCx and RCA. Interestingly, High-density lipoprotein cholesterol showed a dynamic association along DS change in the per-patient analysis.ConclusionsThis study demonstrates the clinical utility of the BQR model for evaluating the comprehensive relationship between risk factors and baseline-grade CAD and its progression. Show less
BACKGROUND The association between the change in vessel inflammation, as quantified by perivascular adipose tissue (PVAT) density, and the progression of coronary atherosclerosis remains to be... Show moreBACKGROUND The association between the change in vessel inflammation, as quantified by perivascular adipose tissue (PVAT) density, and the progression of coronary atherosclerosis remains to be determined.OBJECTIVES The purpose of this study was to explore the association between the change in PVAT density and the progression of total and compositional plaque volume (PV). METHODS Patients were selected from a prospective multinational registry. Patients who underwent serial coronary computed tomography angiography studies with $2-year intervals and were scanned with the same tube voltage at baseline and follow-up were included. Total and compositional PV and PVAT density at baseline and follow-up were quantitatively analyzed for every lesion. Multivariate linear regression models using cluster analyses were constructed.RESULTS A total of 1,476 lesions were identified from 474 enrolled patients (mean age 61.2 +/- 9.3 years; 65.0% men). The mean PVAT density was-74.1 +/- 11.5 HU, and total PV was 48.1 +/- 83.5 mm3 (19.2 +/- 44.8 mm3 of calcified PV and 28.9 +/- 51.0 mm3 of noncalcified PV). On multivariate analysis (adjusted for clinical risk factors, medication use, change in lipid levels, total PV at baseline, luminal HU attenuation, location of lesions, and tube voltage), the increase in PVAT density was positively associated with the progression of total PV (estimate = 0.275 [95% CI: 0.004-0.545]; P = 0.047), driven by the association with fibrous PV (estimate = 0.245 [95% CI: 0.070-0.420]; P = 0.006). Calcified PV progression was not associated with the increase in PVAT density (P > 0.050). CONCLUSIONS Increase in vessel inflammation represented by PVAT density is independently associated with the progression of the lipid component of coronary atherosclerotic plaques. (Progression of AtheRosclerotic PlAque Deter-mIned by Computed TomoGraphic Angiography Imaging [PARADIGM]; NCT02803411) (J Am Coll Cardiol Img 2022;15:1760-1767) (c) 2022 by the American College of Cardiology Foundation. Show less
Objectives: To investigate potential differences in plaque progression (PP) between in East Asians and Caucasians as well as to determine clinical predictors of PP in East Asians. Background:... Show moreObjectives: To investigate potential differences in plaque progression (PP) between in East Asians and Caucasians as well as to determine clinical predictors of PP in East Asians. Background: Studies have demonstrated differences in cardiovascular risk factors as well as plaque burden and progression across different ethnic groups. Methods: The study comprised 955 East Asians (age 60.4 +/- 9.3 years, 50.9% males) and 279 Caucasians (age 60.4 +/- 8.6 years, 74.5% males) who underwent two serial coronary computed tomography angiography (CCTA) studies over a period of at least 24 months. Patients were enrolled and analyzed from the PARADIGM (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging) registry. After propensity-score matching, plaque composition and progression were compared between East Asian and Caucasian patients. Within East Asians, the plaque progression group (defined as plaque volume at follow-up CCTA minus plaque volume at baseline CCTA> 0) was compared to the no PP group to determine clinical predictors for PP in East Asians. Results: In the matched cohort, baseline volumes of total plaque as well as all plaque subtypes were comparable. There was a trend towards increased annualized plaque progression among East Asians compared to Caucasians (18.3 +/- 24.7 mm(3)/year vs 16.6 mm(3)/year, p = 0.054). Among East Asians, 736 (77%) had PP. East Asians with PP had more clinical risk factors and higher plaque burden at baseline (normalized total plaque volume of144.9 +/- 233.3 mm(3) vs 36.6 +/- 84.2 mm(3) for PP and no PP, respectively, p < 0.001). Multivariate logistic regression analysis showed that baseline normalized plaque volume (OR: 1.10, CI: 1.10-1.30, p < 0.001), age (OR: 1.02, CI: 1.00-1.04, p = 0.023) and body mass index (OR: 2.24, CI: 1.01-1.13, p = 0.024) were all predictors of PP in East Asians. Clinical events, driven mainly by percutaneous coronary intervention, were higher among the PP group with a total of 124 (16.8%) events compared to 22 (10.0%) in the no PP group (p = 0.014). Conclusion: East Asians and Caucasians had comparable plaque composition and progression. Among East Asians, the PP group had a higher baseline plaque burden which was associated with greater PP and increased clinical events. Show less
IMPORTANCE Distinct plaque locations and vessel geometric features predispose to altered coronary flow hemodynamics. The association between these lesion-level characteristics assessed by coronary... Show moreIMPORTANCE Distinct plaque locations and vessel geometric features predispose to altered coronary flow hemodynamics. The association between these lesion-level characteristics assessed by coronary computed tomographic angiography (CCTA) and risk of future acute coronary syndrome (ACS) is unknown.OBJECTIVE To examine whether CCTA-derived adverse geometric characteristics (AGCs) of coronary lesions describing location and vessel geometry add to plaque morphology and burden for identifying culprit lesion precursors associated with future ACS.DESIGN, SETTING, AND PARTICIPANTS This substudy of ICONIC (Incident Coronary Syndromes Identified by Computed Tomography), a multicenter nested case-control cohort study, included patients with ACS and a culprit lesion precursor identified on baseline CCTA (n = 116) and propensity score-matched non-ACS controls (n = 116). Data were collected from July 20, 2012, to April 30, 2017, and analyzed from October 1, 2020, to October 31, 2021.EXPOSURES Coronary lesions were evaluated for the following 3 AGCs: (1) distance from the coronary ostium to lesion; (2) location at vessel bifurcations; and (3) vessel tortuosity, defined as the presence of 1 bend of greater than 90 degrees or 3 curves of 45 degrees to 90 degrees using a 3-point angle within the lesion.MAIN OUTCOMES AND MEASURES Association between lesion-level AGCs and risk of future ACS-causing culprit lesions.RESULTS Of 548 lesions, 116 culprit lesion precursors were identified in 116 patients (80 [69.0%] men; mean [SD], age 62.7 [11.5] years). Compared with nonculprit lesions, culprit lesion precursors had a shorter distance from the ostium (median, 35.1 [IQR, 23.6-48.4] mm vs 44.5 [IQR, 28.2-70.8] mm), more frequently localized to bifurcations (85 [73.3%] vs 168 [38.9%]), and had more tortuous vessel segments (5 [4.3%] vs 6 [1.4%]; all P<.05). In multivariable Cox regression analysis, an increasing number of AGCs was associated with a greater risk of future culprit lesions (hazard ratio [HR] for 1 AGC, 2.90 [95% CI, 1.38-6.08]; P=.005; HR for >= 2 AGCs, 6.84 [95% CI, 3.33-14.04]; P<.001). Adverse geometric characteristics provided incremental discriminatory value for culprit lesion precursors when added to a model containing stenosis severity, adverse morphological plaque characteristics, and quantitative plaque characteristics (area under the curve, 0.766 [95% CI, 0.718-0.814] vs 0.733 [95% CI, 0.685-0.782]). In per-patient comparison, patients with ACS had a higher frequency of lesions with adverse plaque characteristics, AGCs, or both compared with control patients (>= 2 adverse plaque characteristics, 70 [60.3%] vs 50 [43.1%]; >= 2 AGCs, 92 [79.3%] vs 60 [51.7%]; >= 2 of both, 37 [31.9%] vs 20 [17.2%]; all P<.05).CONCLUSIONS AND RELEVANCE These findings support the concept that CCTA-derived AGCs capturing lesion location and vessel geometry are associated with risk of future ACS-causing culprit lesions. Adverse geometric characteristics may provide additive prognostic information beyond plaque assessment in CCTA. Show less
OBJECTIVES This study sought to investigate the impact of low tube voltage scanning heterogeneity of coronary luminal attenuation on plaque quantification and characterization with coronary... Show moreOBJECTIVES This study sought to investigate the impact of low tube voltage scanning heterogeneity of coronary luminal attenuation on plaque quantification and characterization with coronary computed tomography angiography (CCTA). BACKGROUND The impact of low tube voltage and coronary luminal attenuation on quantitative coronary plaque remains uncertain. METHODS A total of 1,236 consecutive patients (age: 60 +/- 9 years; 41% female) who underwent serial CCTA at an interval of $2 years were included from an international registry. Patients with prior revascularization or nonanalyzable coronary CTAs were excluded. Total coronary plaque volume was assessed and subclassified based on specific Hounsfield unit (HU) threshold: necrotic core, fibrofatty plaque, and fibrous plaque and dense calcium. Luminal attenuation was measured in the aorta. RESULTS With increasing luminal HU (<350, 350-500, and >500 HU), percent calcified plaque was increased (16%, 27%, and 40% in the median; P < 0.001), and fibrofatty plaque (26%, 13%, and 4%; P < 0.001) and necrotic core (1.6%, 0.3%, and 0.0%; P < 0.001) were decreased. Higher tube voltage scanning (80,100, and 120 kV) resulted in decreasing luminal attenuation (689 +/- 135, 497 +/- 89, and 391 +/- 73 HU; P < 0.001) and calcified plaque volume (59%, 34%, and 23%; P < 0.001) and increased fibrofatty plaque (3%, 9%, and 18%; P < 0.001) and necrotic core (0.2%, 0.1%, and 0.6%; P < 0.001). Mediation analysis showed that the impact of 100 kV on plaque composition, compared with 120 kV, was primarily caused by an indirect effect through blood pool attenuation. Tube voltage scanning of 80 kV maintained a direct effect on fibrofatty plaque and necrotic core in addition to an indirect effect through the luminal attenuation. CONCLUSIONS Low tube voltage usage affected plaque morphology, mainly through an increase in luminal HU with a resultant increase in calcified plaque and a reduction in fibrofatty and necrotic core. These findings should be considered as CCTA-based plaque measures are being used to guide medical management and, in particular, when being used as a measure of treatment response. (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angi-ography Imaging [PARADIGM]; NCT02803411) (J Am Coll Cardiol Img 2021;14:2429-2440) (c) 2021 by the American College of Cardiology Foundation. Show less
Aims 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)... Show moreAims 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).Methods and results 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 <60mL/min/1.73 m(2). 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 (57.53.4 vs. 65.9 +/- 7.7 mm(3)/year, P = 0.28) or annualized (17.3 +/- 1.0 vs. 19.9 +/- 2.0 mm(3)/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 mm(3)/year, P < 0.01) or annualized (16.4 +/- 0.9 vs. 23.9 +/- 2.6 mm(3)/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.Conclusion Decline in renal function was associated with more rapid plaque progression, whereas the presence of CKD was not. Show less
Question Is statin therapy associated with atherosclerotic plaque progression as assessed across a range of density measurements by coronary computed tomography angiography? Findings In this cohort... Show moreQuestion Is statin therapy associated with atherosclerotic plaque progression as assessed across a range of density measurements by coronary computed tomography angiography? Findings In this cohort study assessing serial coronary computed tomography angiographic images of 2458 coronary lesions among 857 patients, untreated coronary lesions progressed in volume for all 6 compositional plaque types-low attenuation (-30 to 75 Hounsfield units [HU]), fibro-fatty (76-130 HU), fibrous (131-350 HU), low-density calcium (351-700 HU), high-density calcium (701-1000 HU), and 1K (>1000 HU) plaque-whereas statin therapy was associated with decreases in low-attenuation and fibro-fatty plaque and with greater progression of high-density calcium and 1K plaque. Statin therapy was not associated with a change in calcified plaque but with a transformation toward more dense calcium, which was associated with slower overall plaque progression. Meaning These results suggest an association of statin use with greater rates of transformation of coronary atherosclerosis toward high-density calcium, supporting the concept of reduced atherosclerotic risk with increased densification of calcium.This cohort study uses coronary computed tomography angiography to investigate whether statin therapy is associated with alterations in the volume or calcium density of 6 compositional atherosclerotic plaque types in patients with coronary artery disease.Importance The density of atherosclerotic plaque forms the basis for categorizing calcified and noncalcified morphology of plaques. Objective To assess whether alterations in plaque across a range of density measurements provide a more detailed understanding of atherosclerotic disease progression. Design, Setting, and Participants This cohort study enrolled 857 patients who underwent serial coronary computed tomography angiography 2 or more years apart and had quantitative measurements of coronary plaques throughout the entire coronary artery tree. The study was conducted from 2013 to 2016 at 13 sites in 7 countries. Main Outcomes and Measures The main outcome was progression of plaque composition of individual coronary plaques. Six plaque composition types were defined on a voxel-level basis according to the plaque attenuation (expressed in Hounsfield units [HU]): low attenuation (-30 to 75 HU), fibro-fatty (76-130 HU), fibrous (131-350 HU), low-density calcium (351-700 HU), high-density calcium (701-1000 HU), and 1K (>1000 HU). The progression rates of these 6 compositional plaque types were evaluated according to the interaction between statin use and baseline plaque volume, adjusted for risk factors and time interval between scans. Plaque progression was also examined based on baseline calcium density. Analysis was performed among lesions matched at baseline and follow-up. Data analyses were conducted from August 2019 through March 2020. Results In total, 2458 coronary lesions in 857 patients (mean [SD] age, 62.1 [8.7] years; 540 [63.0%] men; 548 [63.9%] received statin therapy) were included. Untreated coronary lesions increased in volume over time for all 6 compositional types. Statin therapy was associated with volume decreases in low-attenuation plaque (beta, -0.02; 95% CI, -0.03 to -0.01; P = .001) and fibro-fatty plaque (beta, -0.03; 95% CI, -0.04 to -0.02; P < .001) and greater progression of high-density calcium plaque (beta, 0.02; 95% CI, 0.01-0.03; P < .001) and 1K plaque (beta, 0.02; 95% CI, 0.01-0.03; P < .001). When analyses were restricted to lesions without low-attenuation plaque or fibro-fatty plaque at baseline, statin therapy was not associated with a change in overall calcified plaque volume (beta, -0.03; 95% CI, -0.08 to 0.02; P = .24) but was associated with a transformation toward more dense calcium. Interaction analysis between baseline plaque volume and calcium density showed that more dense coronary calcium was associated with less plaque progression. Conclusions and Relevance The results suggest an association of statin use with greater rates of transformation of coronary atherosclerosis toward high-density calcium. A pattern of slower overall plaque progression was observed with increasing density. All findings support the concept of reduced atherosclerotic risk with increased densification of calcium. Show less
Kim, M.; Lee, S.P.; Kwak, S.; Yang, S.; Kim, Y.J.; Andreini, D.; ... ; Chang, H.J. 2021
Background: The association of age with coronary plaque dynamics is not well characterized by coronary computed tomography angiography (CCTA).Methods: From a multinational registry of patients who... Show moreBackground: The association of age with coronary plaque dynamics is not well characterized by coronary computed tomography angiography (CCTA).Methods: From a multinational registry of patients who underwent serial CCTA, 1153 subjects (61 +/- 5 years old, 61.1% male) were analyzed. Annualized volume changes of total, fibrous, fibrofatty, necrotic core, and dense calcification plaque components of the whole heart were compared by age quartile groups. Clinical events, a composite of all-cause death, acute coronary syndrome, and any revascularization after 30 days of the initial CCTA, were also analyzed. Random forest analysis was used to define the relative importance of age on plaque progression.Results: With a 3.3-years' median interval between the two CCTA, the median annual volume changes of total plaque in each age quartile group was 7.8, 10.5, 10.8, and 12.1 mm(3)/year and for dense calcification, 2.5, 4.6, 5.4, and 7.1 mm(3)/year, both of which demonstrated a tendency to increase by age (p-for-trend = 0.001 and < 0.001, respectively). However, this tendency was not observed in any other plaque components. The annual volume changes of total plaque and dense calcification were also significantly different in the propensity score-matched lowest age quartile group versus the other age groups as was the composite clinical event (log-rank p = 0.003). In random forest analysis, age had comparable importance in the total plaque volume progression as other traditional factors.Conclusions: The rate of whole-heart plaque progression and dense calcification increases depending on age. Age is a significant factor in plaque growth, the importance of which is comparable to other traditional risk factors. Show less
Background: Aortic valve calcification (AVC) is a key feature of aortic stenosis, and patients with aortic stenosis often have coronary-artery disease. Therefore, proving the association between... Show moreBackground: Aortic valve calcification (AVC) is a key feature of aortic stenosis, and patients with aortic stenosis often have coronary-artery disease. Therefore, proving the association between the progression of AVC and coronary atherosclerosis could improve follow-up and treatment strategies.Purpose: To explore the association between the progression of AVC and the progression of total and plaque volume composition from a large multicenter registry of serial coronary CT angiographic examinations.Materials and Methods: A prospective multinational registry (PARADIGM) of consecutive participants who underwent serial coronary CT angiography at intervals of every 2 years or more was performed (January 2003-December 2015). AVC and the total and plaque volume composition at baseline and follow-up angiography were quantitatively analyzed. Plaque volumes were normalized by using the mean total analyzed vessel length of the study population. Multivariable linear mixed-effects models were constructed.Results: Overall, 594 participants (mean age. standard deviation, 62 years. 10; 330 men) were included (mean interval between baseline and follow-up angiography, 3.9 years. 1.5). At baseline, the AVC score was 31 Agatston units. 117, and the normalized total plaque volume at baseline was 122 mm(3)+/- 219. After adjustment for age, sex, clinical risk factors, and medication use, AVC was independently associated with total plaque volume (standardized. = 0.24; 95% CI: 0.16, 0.32; P..001) and both calcified (beta = 0.26; 95% CI: 0.18, 0.34; P<.001) and noncalcified (beta = 0.17; 95% CI: 0.08, 0.25; P..001) plaque volumes at baseline. The progression of AVC was associated with the progression of total plaque volume (beta = 0.13; 95% CI: 0.03, 0.22; P =.01), driven solely by calcified plaque volume (beta = 0.24; 95% CI: 0.14, 0.34; P<.001) but not noncalcified plaque volumes (beta =.0.06; 95% CI:.0.14, 0.03; P =.17).Conclusion: The overall burden of coronary atherosclerosis was associated with aortic valve calcification at baseline. However, the progression of aortic valve calcification was associated with only the progression of calcified plaque volume but not with the -progression of noncalcified plaque volume. (C) RSNA. 2021 Show less
Hwang, D.; Kim, H.J.; Lee, S.P.; Lim, S.; Koo, B.K.; Kim, Y.J.; ... ; Chang, H.J. 2021
OBJECTIVES This study sought to identify distinct patient groups and their association with outcome based on the patient similarity network using quantitative coronary plaque characteristics from... Show moreOBJECTIVES This study sought to identify distinct patient groups and their association with outcome based on the patient similarity network using quantitative coronary plaque characteristics from coronary computed tomography angiography (CTA).BACKGROUND Coronary CTA can noninvasively assess coronary plaques quantitatively.METHODS Patients who underwent 2 coronary CTAs at a minimum of 24 months' interval were analyzed (n = 1,264). A similarity Mapper network of patients was built by topological data analysis (TDA) based on the whole-heart quantitative coronary plaque analysis on coronary CTA to identify distinct patient groups and their association with outcome.RESULTS Three distinct patient groups were identified by TDA, and the patient similarity network by TDA showed a dosed loop, demonstrating a continuous trend of coronary plaque progression. Group A had the least coronary plaque amount (median 12.4 mm(3) [interquartile range (IQR): 0.0 to 39.6 mm(3)]) in the entire coronary tree. Group B had a moderate coronary plaque amount (31.7 mm(3) [IQR: 0.0 to 127.4 mm(3)]) with relative enrichment of fibrofatty and necrotic core (32.6% [IQR: 16.7% to 46.2%] and 2.7% [IQR: 0.1% to 6.9%] of the total plaque, respectively) components. Group C had the largest coronary plaque amount (187.0 mm(3) [IQR: 96.7 to 306.4 mm(3)]) and was enriched for dense calcium component (46.8% [IQR: 32.0% to 63.7%] of the total plaque). At follow-up, total plaque volume, fibrous, and dense calcium volumes increased in all groups, but the proportion of fibrofatty component decreased in groups B and C, whereas the necrotic core portion decreased in only group B (all p< 0.05). Group B showed a higher acute coronary syndrome incidence than other groups (0.3% vs. 2.6% vs. 0.6%; p= 0.009) but both group B and C had a higher revascularization incidence than group A (3.1% vs. 15.5% vs. 17.8%; p < 0.001). Incorporating group information from TDA demonstrated increase of model fitness for predicting acute coronary syndrome or revascularization compared with that incorporating clinical risk factors, percentage diameter stenosis, and high-risk plaque features.CONCLUSIONS The TDA of quantitative whole-heart coronary plaque characteristics on coronary CTA identified distinct patient groups with different plaque dynamics and clinical outcomes. (Progression of AtheRosclerotic PlAque Determined by Computed TomoGraphic Angiography Imaging [PARADIGM]; NCT02803411) (C) 2021 by the American College of Cardiology Foundation. Show less
Aims Anatomic series commonly report the extent and severity of coronary artery disease (CAD), regardless of location. The aim of this study was to evaluate differences in atherosclerotic plaque... Show moreAims Anatomic series commonly report the extent and severity of coronary artery disease (CAD), regardless of location. The aim of this study was to evaluate differences in atherosclerotic plaque burden and composition across the major epicardial coronary arteries.Methods and results A total of 1271 patients (age 60 +/- 9 years; 57% men) with suspected CAD prospectively underwent coronary computed tomography angiography (CCTA). Atherosclerotic plaque volume was quantified with categorization by composition (necrotic core, fibrofatty, fibrous, and calcified) based on Hounsfield Unit density. Per-vessel measures were compared using generalized estimating equation models. On CCTA, total plaque volume was lowest in the LCx (10.0 +/- 29.4 mm(3)), followed by the RCA (32.8 +/- 82.7 mm(3); P < 0.001), and LAD (58.6 +/- 83.3 mm(3); P < 0.001), even when correcting for vessel length or volume. The prevalence of >= 2 high-risk plaque features, such as positive remodelling or spotty calcification, occurred less in the LCx (3.8%) when compared with the LAD (21.4%) or RCA (10.9%, P < 0.001). In the LCx, the most stenotic lesion was categorized as largely calcified more often than in the RCA and LAD (55.3% vs. 39.4% vs. 32.7%; P<0.001). Median diameter stenosis was also lowest in the LCx (16.2%) and highest in the LAD (21.3%; P<0.001) and located more distal along the LCx when compared with the RCA and LAD (P < 0.001).Conclusion Atherosclerotic plaque, irrespective of vessel volume, varied across the epicardial coronary arteries; with a significantly lower burden and different compositions in the LCx when compared with the LAD and RCA. These volumetric and compositional findings support a diverse milieu for atherosclerotic plaque development and may contribute to a varied acute coronary risk between the major epicardial coronary arteries.[GRAPHICS]. Show less
OBJECTIVES The aim of the current study was to explore the impact of plaque calcification in terms of absolute calcified plaque volume (CPV) and in the context of its percentage of the total plaque... Show moreOBJECTIVES The aim of the current study was to explore the impact of plaque calcification in terms of absolute calcified plaque volume (CPV) and in the context of its percentage of the total plaque volume at a lesion and patient level on the progression of coronary artery disease.BACKGROUND Coronary artery calcification is an established marker of risk of future cardiovascular events. Despite this, plaque calcification is also considered a marker of plaque stability, and it increases in response to medical therapy.METHODS This analysis included 925 patients with 2,568 lesions from the PARADIGM (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging) registry, in which patients underwent clinically indicated serial coronary computed tomography angiography. Plaque calcification was examined by using CPV and percent CPV (PCPV), calculated as (CPV/plaque volume) x 100 at a per-plaque and per-patient level (summation of all individual plaques).RESULTS CPV was strongly correlated with plaque volume (r = 0.780; p < 0.001) at baseline and with plaque progression (r = 0.297; p < 0.001); however, this association was reversed after accounting for plaque volume at baseline (r = -0146; p < 0.001). In contrast, PCPV was an independent predictor of a reduction in plaque volume (r = -0.11; p < 0.001) in univariable and multivariable linear regression analyses. Patient-level analysis showed that high CPV was associated with incident major adverse cardiac events (hazard ratio: 3.01: 95% confidence interval: 1.58 to 5.72), whereas high PCPV was inversely associated with major adverse cardiac events (hazard ratio: 0.529; 95% confidence interval: 0.229 to 0.968) in multivariable analysis.CONCLUSIONS Calcified plaque is a marker for risk of adverse events and disease progression due to its strong association with the total plaque burden. When considered as a percentage of the total plaque volume, increasing PCPV is a marker of plaque stability and reduced risk at both a lesion and patient level. (C) 2021 by the American College of Cardiology Foundation. Show less
Aims Although there is increasing evidence supporting coronary atherosclerosis evaluation by coronary computed tomography angiography (CCTA), no data are available on age and sex differences for... Show moreAims Although there is increasing evidence supporting coronary atherosclerosis evaluation by coronary computed tomography angiography (CCTA), no data are available on age and sex differences for quantitative plaque features. The aim of this study was to investigate sex and age differences in both qualitative and quantitative atherosclerotic features from CCTA prior to acute coronary syndrome (ACS).Methods and results Within the ICONIC study, in which 234 patients with subsequent ACS were propensity matched 1:1 with 234 non-event controls, our current subanalysis included only the ACS cases. Both qualitative and quantitative advance plaque analysis by CCTA were performed by a core laboratory. In 129 cases, culprit lesions identified by invasive coronary angiography at the time of ACS were co-registered to baseline CCTA precursor lesions. The study population was then divided into subgroups according to sex and age (<65 vs. = 65 years old) for analysis. Older patients had higher total plaque volume than younger patients. Within specific subtypes of plaque volume, however, only calcified plaque volume was higher in older patients (135.9 +/- 163.7 vs. 63.8 +/- 94.2 mm(3), P < 0.0001, respectively). Although no sex-related differences were recorded for calcified plaque volume, females had lower fibrous and fibrofatty plaque volume than males (Fibrofatty volume 29.6 +/- 44.1 vs. 75.3 +/- 98.6 mm(3), P = 0.0001, respectively). No sex-related differences in the prevalence of qualitative high-risk plaque features were found, even after separate analyses considering age were performed.Conclusion Our data underline the importance of age- and sex-related differences in coronary atherosclerosis presentation, which should be considered during CCTA-based atherosclerosis quantification. Show less
OBJECTIVES This study sought to explore sex-based differences in total and compositional plaque volume (PV) progression.BACKGROUND It is unclear whether sex has an impact on PV progression in... Show moreOBJECTIVES This study sought to explore sex-based differences in total and compositional plaque volume (PV) progression.BACKGROUND It is unclear whether sex has an impact on PV progression in patients with coronary artery disease (CAD).METHODS The study analyzed a prospective multinational registry of consecutive patients with suspected CAD who underwent 2 or more clinically indicated coronary computed tomography angiography (CTA) at $2-year intervals. Total and compositional PV at baseline and follow-up were quantitatively analyzed and normalized using the analyzed total vessel length. Multivariate linear regression models were constructed.RESULTS Of the 1,255 patients included (median coronary CTA interval 3.8 years), 543 were women and 712 were men. Women were older (62 +/- 9 years of age vs. 59 +/- 9 years of age; p < 0.001) and had higher total cholesterol levels (195 +/- 41 mg/dl vs. 187 +/- 39 mg/dl; p = 0.002). Prevalence of hypertension, diabetes, and family history of CAD were not different (all p > 0.05). At baseline, men possessed greater total PV (31.3 mm(3) [interquartile range (IQR): 0 to 121.8 mm(3)] vs. 56.7 mm(3) [IQR: 6.8 to 152.1 mm(3)] p = 0.005), and there was an approximately 9-year delay in women in developing total PV than in men. The prevalence of high-risk plaques was greater in men than women (31% vs. 20%; p < 0.001). In multivariate analysis, after adjusting for age, clinical risk factors, medication use, and total PV at baseline, despite similar total PV progression rates, female sex was associated with greater calcified PV progression (b = 2.83; p = 0.004) but slower noncalcified PV progression (b = -3.39; p = 0.008) and less development of high-risk plaques (b = -0.18; p = 0.049) than in men.CONCLUSIONS The compositional PV progression differed according to sex, suggesting that comprehensive plaque evaluation may contribute to further refining of risk stratification according to sex. (c) 2020 by the American College of Cardiology Foundation. Show less
OBJECTIVES This study sought to identify culprit lesion (CL) precursors among acute coronary syndrome (ACS) patients based on qualitative and quantitative computed tomography-based plaque... Show moreOBJECTIVES This study sought to identify culprit lesion (CL) precursors among acute coronary syndrome (ACS) patients based on qualitative and quantitative computed tomography-based plaque characteristics.BACKGROUND Coronary computed tomography angiography (CTA) has been validated for patient-level prediction of ACS. However, the applicability of coronary CTA to CL assessment is not known.METHODS Utilizing the ICONIC (Incident COroNary Syndromes Identified by Computed Tomography) study, a nested casecontrol study of 468 patients with baseline coronary CTA, the study included ACS patients with invasive coronary angiography-adjudicated CLs that could be aligned to CL precursors on baseline coronary CTA. Separate blinded core laboratories adjudicated CLs and performed atherosclerotic plaque evaluation. Thereafter, the study used a boosted ensemble algorithm (XGBoost) to develop a predictive model of CLs. Data were randomly split into a training set (80%) and a test set (20%). The area under the receiver-operating characteristic curve of thismodel was compared with that of diameter stenosis (model 1), high-risk plaque features (model 2), and lesion-level features of CL precursors from the ICONIC study (model 3). Thereafter, the machine learning (ML) model was applied to 234 non-ACS patients with 864 lesions to determine model performance for CL exclusion.RESULTS CL precursors were identified by both coronary angiography and baseline coronary CTA in 124 of 234 (53.0%) patients, with a total of 582 lesions (containing 124 CLs) included in the analysis. The ML model demonstrated significantly higher area under the receiver-operating characteristic curve for discriminating CL precursors (0.774; 95% confidence interval [CI]: 0.758 to 0.790) compared with model 1 (0.599; 95% CI: 0.599 to 0.599; p < 0.01), model 2 (0.532; 95% CI: 0.501 to 0.563; p < 0.01), and model 3 (0.672; 95% CI: 0.662 to 0.682; p < 0.01). When applied to the non-ACS cohort, the ML model had a specificity of 89.3% for excluding CLs.CONCLUSIONS In a high-risk cohort, a boosted ensemble algorithm can be used to predict CL from non-CL precursors on coronary CTA. (c) 2020 by the American College of Cardiology Foundation. Show less
Aims High-risk plaque (HRP) and non-obstructive coronary artery disease independently predict adverse events, but their importance to future culprit lesions has not been resolved. We sought to... Show moreAims High-risk plaque (HRP) and non-obstructive coronary artery disease independently predict adverse events, but their importance to future culprit lesions has not been resolved. We sought to determine in patients prior to confirmed acute coronary syndrome (ACS) the association between lesion percent diameter stenosis (%DS), and the absolute number and prevalence of HRP. The secondary objective was to examine the relative importance of non-obstructive HRP in future culprit lesions.Methods and results Within the ICONIC study, a nested case-control study of patients undergoing coronary computed tomographic angiography (coronary CT), we included ACS cases with culprit lesions confirmed by invasive coronary angiography and coregistered to baseline coronary CT. Quantitative CT was used to evaluate obstructive (>= 50%) and non-obstructive (<50%) diameter stenosis, with HRP defined as >= 2 features of spotty calcification, positive remodelling, or low-attenuation plaque at baseline. A total of 234 patients with downstream ACS over 54 (interquartile range 5-525.5) days exhibited 198/898 plaques with HRP on coronary CT. While HRP was less prevalent in non-obstructive (19.7%, 161/819) than obstructive lesions (46.8%, 37/79, P < 0.001), non-obstructive plaque comprised 81.3% (161/198) of HRP lesions overall. Among the 128 patients with identifiable culprit lesion precursors, the adjusted hazard ratio (HR) was 1.85 [95% confidence interval (CI) 1.26-2.72] for HRP, with no interaction between %DS and HRP (P = 0.82). Compared to non-obstructive HRP lesions, obstructive lesions without HRP exhibited a non-significant HR of 1.41 (95% CI 0.61-3.25, P = 0.42).Conclusions While HRP is more prevalent among obstructive lesions, non-obstructive HRP lesions outnumber those that are obstructive and confer risk clinically approaching that of obstructive lesions without HRP. Show less
Background and aims: Different methodologies to report whole-heart atherosclerotic plaque on coronary computed tomography angiography (CCTA) have been utilized. We examined which of the three... Show moreBackground and aims: Different methodologies to report whole-heart atherosclerotic plaque on coronary computed tomography angiography (CCTA) have been utilized. We examined which of the three commonly used plaque burden definitions was least affected by differences in body surface area (BSA) and sex.Methods: The PARADIGM study includes symptomatic patients with suspected coronary atherosclerosis who underwent serial CCTA > 2 years apart. Coronary lumen, vessel, and plaque were quantified from the coronary tree on a 0.5 mm cross-sectional basis by a core-lab, and summed to per-patient. Three quantitative methods of plaque burden were employed: (1) total plaque volume (PV) in mm(3), (2) percent atheroma volume (PAV) in % [which equaled: PV/vessel volume * 100%], and (3) normalized total atheroma volume (TAV(norm)) in mm(3) [which equaled: PV/vessel length * mean population vessel length]. Only data from the baseline CCTA were used. PV, PAV, and TAV(norm), were compared between patients in the top quartile of BSA vs the remaining, and between sexes. Associations between vessel volume, BSA, and the three plaque burden methodologies were assessed.Results: The study population comprised 1479 patients (age 60.7 +/- 9.3 years, 58.4% male) who underwent CCTA. A total of 17,649 coronary artery segments were evaluated with a median of 12 (IQR 11-13) segments per-patient (from a 16-segment coronary tree). Patients with a large BSA (top quartile), compared with the remaining patients, had a larger PV and TAV(norm), but similar PAV. The relation between larger BSA and larger absolute plaque volume (PV and TAV(norm)) was mediated by the coronary vessel volume. Independent from the atherosclerotic cardiovascular disease risk (ASCVD) score, vessel volume correlated with PV (P < 0.001), and (P = 0.003), but not with PAV (P = 0.201). The three plaque burden methods were equally affected by sex.Conclusions: PAV was less affected by patients body surface area then PV and TAV(norm) and may be the preferred method to report coronary atherosclerotic burden. Show less
