Progression Of Atherosclerotic Plaque Determined By Computed Tomographic Angiography Imaging Research Articles

Low HDL cholesterol and hyperglicemia are metabolic syndrome components associated with plaque progression in patients with chronic coronary syndrome: a PARADIGM study

Abstract Background The metabolic syndrome (MetS), a cluster of dyslipidemia, hyperglicemia and hypertension predicts future cardiovascular disease and death in general populations. Purpose We aimed to assess whether MetS and its components may impact on coronary plaque progression (PP), at serial coronary computed tomography angiography (CCTA), and major adverse cardiovascular events (MACE) in patients with chronic coronary syndrome (CCS). Methods A total of 1200 CCS patients (aged 60.9±9.3 years, 55.4% male) who underwent serial CCTA (≥2 years apart) and had available data on glucose/lipid metabolism and outcome, were analysed from the Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging (PARADIGM) registry. MetS and its components were categorized according to NCEPT ATPIII definition. Plaque volumes were measured in coronary segments (≥ 2 mm in diameter) and summed to provide total plaque volume (PV, mm3) and percent atheroma volume (PV/vessel volume*100) (PAV, %) per patient at baseline and follow-up. Rapid PP was defined as annualized PAV increase (∆PAV) ≥1.0%/year. MACE included non-fatal myocardial infarction, any cause death and unplanned coronary revascularization (>30 days after first CCTA). Results MetS was present in 366 patients (31%). The median interscan period was 3.2 years (IQR 1.9) and rapid PP occurred in 341 patients (28%). MetS was associated with a higher total PV (133±183 vs 97±163, P<0.001) and PAV (7.1±9.3 vs 5.4±8.0, P<0.001) at baseline and a higher annual change in both PV (18.5±23.4 vs 13.9±22.5, P< 0.001) and PAV (0.9±1.1 vs 0.7±1.0, P<0.001) (Figure 1A). At a multivariable logistic regression analysis, MetS independently predicted rapid PP (OR 1.50, 95%CI 1.11-2.02, p<0.01) after adjustment for other risk factors not included among its components (age, gender, smoking habits, family history, hypercholesterolemia, previous CAD), statin treatment and baseline PAV. Among MetS components, diabetes under treatment or fasting plasma glucose >100 mg/dL (OR 1.37, 95%CI 1.02-1.84, p<0.05) and low HDL cholesterol (<40 mg/dL in males and < 50 mg/dL in females) (OR 1.76, 95%CI 1.29-2.39, p<0.001) were independently associated with rapid PP. They had an additive effect on baseline PAV and annualized PAV increase (Figure 1B). The median follow-up duration was 8.23 years (IQR 3.61). MACE occurred in 201 patients (16.8%) (17 death, 11 non-fatal MI, 173 unplanned revascularizations). At multivariable Cox regression analysis, rapid PP was a strong and independent predictor of events (HR 1.72, 95% CI 1.29-2.28, P<0.001) after correction for all risk factors including MeS or its components and baseline PAV. Conclusions Independently of other risk factors and treatment MetS is associated with a higher coronary atherosclerotic burden and rapid PP which are in turn strong predictors of MACE in patients with CCS. Among MetS components hyperglycemia and low HDL-C are major determinants of rapid PP.Figure 1

Progression of non-obstructive coronary plaque: a practical CCTA-based risk score from the PARADIGM registry.

No clear recommendations are endorsed by the different scientific societies on the clinical use of repeat coronary computed tomography angiography (CCTA) in patients with non-obstructive coronary artery disease (CAD). This study aimed to develop and validate a practical CCTA risk score to predict medium-term disease progression in patients at a low-to-intermediate probability of CAD. Patients were part of the Progression of AtheRosclerotic PlAque Determined by Computed Tomographic Angiography Imaging (PARADIGM) registry. Specifically, 370 (derivation cohort) and 219 (validation cohort) patients with two repeat, clinically indicated CCTA scans, non-obstructive CAD, and absence of high-risk plaque (≥ 2 high-risk features) at baseline CCTA were included. Disease progression was defined as the new occurrence of ≥ 50% stenosis and/or high-risk plaque at follow-up CCTA. In the derivation cohort, 104 (28%) patients experienced disease progression. The median time interval between the two CCTAs was 3.3years (2.7-4.8). Odds ratios for disease progression derived from multivariable logistic regression were as follows: 4.59 (95% confidence interval: 1.69-12.48) for the number of plaques with spotty calcification, 3.73 (1.46-9.52) for the number of plaques with low attenuation component, 2.71 (1.62-4.50) for 25-49% stenosis severity, 1.47 (1.17-1.84) for the number of bifurcation plaques, and 1.21 (1.02-1.42) for the time between the two CCTAs. The C-statistics of the model were 0.732 (0.676-0.788) and 0.668 (0.583-0.752) in the derivation and validation cohorts, respectively. The new CCTA-based risk score is a simple and practical tool that can predict mid-term CAD progression in patients with known non-obstructive CAD. The clinical implementation of this new CCTA-based risk score can help promote the management of patients with non-obstructive coronary disease in terms of timing of imaging follow-up and therapeutic strategies. • No recommendations are available on the use of repeat CCTA in patients with non-obstructive CAD. • This new CCTA score predicts mid-term CAD progression in patients with non-obstructive stenosis at baseline. • This new CCTA score can help guide the clinical management of patients with non-obstructive CAD.

Clinical and Coronary Plaque Predictors of Atherosclerotic Nonresponse to Statin Therapy

BackgroundStatins 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.

Glycemic control is independently associated with rapid progression of coronary atherosclerosis in the absence of a baseline coronary plaque burden: a retrospective case–control study from the PARADIGM registry

BackgroundThe baseline coronary plaque burden is the most important factor for rapid plaque progression (RPP) in the coronary artery. However, data on the independent predictors of RPP in the absence of a baseline coronary plaque burden are limited. Thus, this study aimed to investigate the predictors for RPP in patients without coronary plaques on baseline coronary computed tomography angiography (CCTA) images.MethodsA total of 402 patients (mean age: 57.6 ± 10.0 years, 49.3% men) without coronary plaques at baseline who underwent serial coronary CCTA were identified from the Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging (PARADIGM) registry and included in this retrospective study. RPP was defined as an annual change of ≥ 1.0%/year in the percentage atheroma volume (PAV).ResultsDuring a median inter-scan period of 3.6 years (interquartile range: 2.7–5.0 years), newly developed coronary plaques and RPP were observed in 35.6% and 4.2% of the patients, respectively. The baseline traditional risk factors, i.e., advanced age (≥ 60 years), male sex, hypertension, diabetes mellitus, hyperlipidemia, obesity, and current smoking status, were not significantly associated with the risk of RPP. Multivariate linear regression analysis showed that the serum hemoglobin A1c level (per 1% increase) measured at follow-up CCTA was independently associated with the annual change in the PAV (β: 0.098, 95% confidence interval [CI]: 0.048–0.149; P < 0.001). The multiple logistic regression models showed that the serum hemoglobin A1c level had an independent and positive association with the risk of RPP. The optimal predictive cut-off value of the hemoglobin A1c level for RPP was 7.05% (sensitivity: 80.0%, specificity: 86.7%; area under curve: 0.816 [95% CI: 0.574–0.999]; P = 0.017).ConclusionIn this retrospective case–control study, the glycemic control status was strongly associated with the risk of RPP in patients without a baseline coronary plaque burden. This suggests that regular monitoring of the glycemic control status might be helpful for preventing the rapid progression of coronary atherosclerosis irrespective of the baseline risk factors. Further randomized investigations are necessary to confirm the results of our study.Trial registrationClinicalTrials.gov NCT02803411.

Comparison of coronary atherosclerotic plaque progression in East Asians and Caucasians by serial coronary computed tomographic angiography: A PARADIGM substudy

ObjectivesTo 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. BackgroundStudies have demonstrated differences in cardiovascular risk factors as well as plaque burden and progression across different ethnic groups. MethodsThe 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. ResultsIn 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 ​mm3/year vs 16.6 ​mm3/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 ​mm3 vs 36.6 ​± ​84.2 ​mm3 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). ConclusionEast 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.

The Relationship Between Coronary Calcification and the Natural History of Coronary Artery Disease

ObjectivesThe 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. BackgroundCoronary 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. MethodsThis 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) × 100 at a per-plaque and per-patient level (summation of all individual plaques). ResultsCPV 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 = –0.146; 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. ConclusionsCalcified 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. (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging [PARADIGM]; NCT02803411)

Association of Cardiovascular Disease Risk Factor Burden With Progression of Coronary Atherosclerosis Assessed by Serial Coronary Computed Tomographic Angiography

Several studies have reported that the progression of coronary atherosclerosis, as measured by serial coronary computed tomographic (CT) angiography, is associated with the risk of future cardiovascular events. However, the cumulative consequences of multiple risk factors for plaque progression and the development of adverse plaque characteristics have not been well characterized. To examine the association of cardiovascular risk factor burden, as assessed by atherosclerotic cardiovascular disease (ASCVD) risk score, with the progression of coronary atherosclerosis and the development of adverse plaque characteristics. This cohort study is a subgroup analysis of participant data from the prospective observational Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging (PARADIGM) study, which evaluated the association between serial coronary CT angiography findings and clinical presentation. The PARADIGM international multicenter registry, which includes 13 centers in 7 countries (Brazil, Canada, Germany, Italy, Portugal, South Korea, and the US), was used to identify 1005 adult patients without known coronary artery disease who underwent serial coronary CT angiography scans (median interscan interval, 3.3 years; interquartile range [IQR], 2.6-4.8 years) between December 24, 2003, and December 16, 2015. Based on the 10-year ASCVD risk score, the cardiovascular risk factor burden was classified as low (<7.5%), intermediate (7.5%-20.0%), or high (>20.0%). Data were analyzed from February 8, 2019, to April 17, 2020. Association of baseline ASCVD risk burden with plaque progression. Noncalcified plaque, calcified plaque, and total plaque volumes (mm3) were measured. Noncalcified plaque was subclassified using predefined Hounsfield unit thresholds for fibrous, fibrofatty, and low-attenuation plaque. The percent atheroma volume (PAV) was defined as plaque volume divided by vessel volume. Adverse plaque characteristics were defined as the presence of positive remodeling, low-attenuation plaque, or spotty calcification. In total, 1005 patients (mean [SD] age, 60 [8] years; 575 men [57.2%]) were included in the analysis. Of those, 463 patients (46.1%) had a low 10-year ASCVD risk score (low-risk group), 373 patients (37.1%) had an intermediate ASCVD risk score (intermediate-risk group), and 169 patients (16.8%) had a high ASCVD risk score (high-risk group). The annualized progression rate of PAV for total plaque, calcified plaque, and noncalcified plaque was associated with increasing ASCVD risk (r = 0.26 for total plaque, r = 0.23 for calcified plaque, and r = 0.11 for noncalcified plaque; P < .001). The annualized PAV progression of total plaque, calcified plaque, and noncalcified plaque was significantly greater in the high-risk group compared with the low-risk and intermediate-risk groups (for total plaque, 0.99% vs 0.45% and 0.58%, respectively; P < .001; for calcified plaque, 0.61% vs 0.23% and 0.36%; P < .001; and for noncalcified plaque, 0.38%vs 0.22% and 0.23%; P = .01). When further subclassified by noncalcified plaque type, the annualized PAV progression of fibrofatty and low-attenuation plaque was greater in the high-risk group (0.09% and 0.02%, respectively) compared with the low- to intermediate-risk group (n = 836; 0.02% [P = .02] and 0.001% [P = .008], respectively). The interval development of adverse plaque characteristics was greater in the high-risk group compared with the low-risk and intermediate-risk groups (for new positive remodeling, 73 patients [43.2%] vs 151 patients [32.6%] and 133 patients [35.7%], respectively; P = .02; for new low-attenuation plaque, 26 patients [15.4%] vs 44 patients [9.5%] and 35 patients [9.4%]; P = .02; and for new spotty calcification, 37 patients [21.9%] vs 52 patients [11.2%] and 54 patients [14.5%]; P = .002). The progression of noncalcified plaque subclasses and the interval development of adverse plaque characteristics did not significantly differ between the low-risk and intermediate-risk groups. Progression of coronary atherosclerosis occurred across all ASCVD risk groups and was associated with an increase in 10-year ASCVD risk. The progression of fibrofatty and low-attenuation plaques and the development of adverse plaque characteristics was greater in patients with a high risk of ASCVD.

Quantitative assessment of coronary plaque volume change related to triglyceride glucose index: The Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging (PARADIGM) registry

BackgroundThe association between triglyceride glucose (TyG) index and coronary atherosclerotic change remains unclear. We aimed to evaluate the association between TyG index and coronary plaque progression (PP) using serial coronary computed tomography angiography (CCTA).MethodsA total of 1143 subjects (aged 60.7 ± 9.3 years, 54.6% male) who underwent serial CCTA with available data on TyG index and diabetic status were analyzed from The Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging (PARADIGM) registry. PP was defined as plaque volume (PV) (mm3) at follow-up minus PV at index > 0. Annual change of PV (mm3/year) was defined as PV change divided by inter-scan period. Rapid PP was defined as the progression of percent atheroma volume (PV divided by vessel volume multiplied by 100) ≥ 1.0%/year.ResultsThe median inter-scan period was 3.2 (range 2.6–4.4) years. All participants were stratified into three groups based on TyG index tertiles. The overall incidence of PP was 77.3%. Baseline total PV (group I [lowest]: 30.8 (0.0–117.7), group II: 47.2 (6.2–160.4), and group III [highest]: 57.5 (8.4–154.3); P < 0.001) and the annual change of total PV (group I: 5.7 (0.0–20.2), group II: 7.6 (0.5–23.5), and group III: 9.4 (1.4–27.7); P = 0.010) were different among all groups. The risk of PP (odds ratio [OR] 1.648; 95% confidence interval [CI] 1.167–2.327; P = 0.005) and rapid PP (OR 1.777; 95% CI 1.288–2.451; P < 0.001) was increased in group III compared to that in group I. TyG index had a positive and significant association with an increased risk of PP and rapid PP after adjusting for confounding factors.ConclusionTyG index is an independent predictive marker for the progression of coronary atherosclerosis.Clinical registration ClinicalTrials.gov NCT02803411

Burden Of Noncalcified Plaque And Obstructive Stenosis By The Extent Of Coronary Artery Calcium Score: Results From The Progression Of Atherosclerotic Plaque Determined By Computed Tomographic Angiography Imaging (PARADIGM) Registry

Burden Of Noncalcified Plaque And Obstructive Stenosis By The Extent Of Coronary Artery Calcium Score: Results From The Progression Of Atherosclerotic Plaque Determined By Computed Tomographic Angiography Imaging (PARADIGM) Registry

Machine Learning Framework to Identify Individuals at Risk of Rapid Progression of Coronary Atherosclerosis: From the PARADIGM Registry.

BackgroundRapid coronary plaque progression (RPP) is associated with incident cardiovascular events. To date, no method exists for the identification of individuals at risk of RPP at a single point in time. This study integrated coronary computed tomography angiography–determined qualitative and quantitative plaque features within a machine learning (ML) framework to determine its performance for predicting RPP.Methods and ResultsQualitative and quantitative coronary computed tomography angiography plaque characterization was performed in 1083 patients who underwent serial coronary computed tomography angiography from the PARADIGM (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging) registry. RPP was defined as an annual progression of percentage atheroma volume ≥1.0%. We employed the following ML models: model 1, clinical variables; model 2, model 1 plus qualitative plaque features; model 3, model 2 plus quantitative plaque features. ML models were compared with the atherosclerotic cardiovascular disease risk score, Duke coronary artery disease score, and a logistic regression statistical model. 224 patients (21%) were identified as RPP. Feature selection in ML identifies that quantitative computed tomography variables were higher‐ranking features, followed by qualitative computed tomography variables and clinical/laboratory variables. ML model 3 exhibited the highest discriminatory performance to identify individuals who would experience RPP when compared with atherosclerotic cardiovascular disease risk score, the other ML models, and the statistical model (area under the receiver operating characteristic curve in ML model 3, 0.83 [95% CI 0.78–0.89], versus atherosclerotic cardiovascular disease risk score, 0.60 [0.52–0.67]; Duke coronary artery disease score, 0.74 [0.68–0.79]; ML model 1, 0.62 [0.55–0.69]; ML model 2, 0.73 [0.67–0.80]; all P<0.001; statistical model, 0.81 [0.75–0.87], P=0.128).ConclusionsBased on a ML framework, quantitative atherosclerosis characterization has been shown to be the most important feature when compared with clinical, laboratory, and qualitative measures in identifying patients at risk of RPP.

P3380Longitudinal assessment of coronary atherosclerosis according to baseline and changes of serum hemoglobin level

Abstract Introduction Little is known regarding the impact of serum hemoglobin level changes (Δ hemoglobin) on coronary plaque volume. This study evaluated the association between Δ hemoglobin and coronary plaque volume change (PVC) using serial coronary computed tomographic angiography (CCTA). Methods A total of 830 subjects (61±10 years, 51.9% male) who underwent serial CCTA with available hemoglobin levels were analyzed from the Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging (PARADIGM) registry. The median inter-scan period was 3.2 (2.5 to 4.4) years. Quantitative assessment of coronary plaques was performed at both scans. All participants were stratified into four groups based on the quartile of baseline hemoglobin levels. Annualized PVC was defined as total PVC divided by inter-scan period. Plaque progression (PP) was defined as plaque volume at follow-up minus plaque volume at index &gt;0. Results Baseline total plaque volume (mm3) was not different among all groups (group I [lowest]: 34.1 (0.0–127.4) vs. group II: 28.8 (0.0–123.0) vs. group III: 49.9 (5.6–135.0) vs. group IV [highest]: 34.3 (0.0–130.7); p=0.235). During follow-up, Δ hemoglobin was related to annualized PVC (β:−0.114; p=0.001) and PP (odds ratio: 0.868; 95% confidence interval: 0.770–0.978; p=0.020). Multiple linear regression models showed that Δ hemoglobin significantly impacted on annualized PVC in only the composite of I and II groups. Conclusion Based on serial CCTA findings, Δ hemoglobin independently impacted on coronary PVC in individuals with low to normal baseline hemoglobin level.

Differential association between the progression of coronary artery calcium score and coronary plaque volume progression according to statins: the Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging (PARADIGM) study.

Coronary artery calcium score (CACS) is a strong predictor of major adverse cardiac events (MACE). Conversely, statins, which markedly reduce MACE risk, increase CACS. We explored whether CACS progression represents compositional plaque volume (PV) progression differently according to statin use. From a prospective multinational registry of consecutive patients (n = 2252) who underwent serial coronary computed tomography angiography (CCTA) at a ≥ 2-year interval, 654 patients (61 ± 10 years, 56% men, inter-scan interval 3.9 ± 1.5 years) with information regarding the use of statins and having a serial CACS were included. Patients were divided into non-statin (n = 246) and statin-taking (n = 408) groups. Coronary PVs (total, calcified, and non-calcified; sum of fibrous, fibro-fatty, and lipid-rich) were quantitatively analysed, and CACS was measured from both CCTAs. Multivariate linear regression models were constructed for both statin-taking and non-statin group to assess the association between compositional PV change and change in CACS. In multivariate linear regression analysis, in the non-statin group, CACS increase was positively associated with both non-calcified (β = 0.369, P = 0.004) and calcified PV increase (β = 1.579, P < 0.001). However, in the statin-taking group, CACS increase was positively associated with calcified PV change (β = 0.756, P < 0.001) but was negatively associated with non-calcified PV change (β = -0.194, P = 0.026). In the non-statin group, CACS progression indicates the progression of both non-calcified and calcified PV progression. However, under the effect of statins, CACS progression indicates only calcified PV progression, but not non-calcified PV progression. Thus, the result of serial CACS should be differently interpreted according to the use of statins.

Longitudinal assessment of coronary plaque volume change related to glycemic status using serial coronary computed tomography angiography: A PARADIGM (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging) substudy

BackgroundData on the impact of glycemic status on coronary plaque progression have been limited. This study evaluated the association between glycemic status and coronary plaque volume change (PVC) using coronary computed tomography angiography (CCTA). MethodsA total of 1296 subjects (61 ± 9, 56.9% male) who underwent serial CCTA with available glycemic status were enrolled and analyzed from the Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging (PARADIGM) registry. The median inter-scan period was 3.2 (2.6–4.4) years. Quantitative assessment of coronary plaques was performed at both scans. All participants were categorized into the following groups according to glycemic status: normal, pre-diabetes (pre-DM), and diabetes mellitus (DM). ResultsDuring the follow-up, significant differences in PVC (normal: 51.3 ± 83.3 mm3 vs. pre-DM: 51.0 ± 84.3 mm3 vs. DM: 72.6 ± 95.0 mm3; p < 0.001) and annualized PVC (normal: 14.9 ± 24.9 mm3 vs. pre-DM: 15.7 ± 23.8 mm3 vs. DM: 21.0 ± 27.7 mm3; p = 0.001) were observed among the 3 groups. Compared with normal individuals, individuals with pre-DM showed no significant differences in the adjusted odds ratio (OR) for plaque progression (PP) (1.338, 95% confidence interval [CI] 0.967–1.853; p = 0.079). However, the adjusted OR for PP was higher in DM individuals than in normal individuals (1.635, 95% CI 1.126–2.375; p = 0.010). ConclusionDM had an incremental impact on coronary PP, but pre-DM appeared to have no significant association with an increased risk of coronary PP after adjusting for confounding factors. Clinical trial registrationClinicalTrials.govNCT02803411.

In This Issue of the Journal

I want to welcome you to the July 2018 issue of Circulation: Cardiovascular Imaging . The original articles and imaging cases highlight the fundamental role imaging plays in a variety of cardiovascular diseases as well as signals future advances to the field. Detailed below are short summaries of each of these offerings. Lee and colleagues have attempted to address the key question of whether coronary computed tomography angiography–derived measures of atherosclerosis assessment (eg, total atheroma burden or high-risk plaque assessment) provide any additional information with respect to disease progression or clinical events compared with more traditional measures of coronary artery stenosis evaluation. Data mining the PARADIGM (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging) registry, these authors demonstrate that coronary computed tomography angiography measures of plaque burden and evidence of high-risk plaque features further improved the prediction of plaque progression and major averse cardiac evens. In his editorial, Arbab-Zadeh contextualizes these results, pointing out that although the magnitude of incremental risk prediction was small and of unclear clinical significance, such information may prove useful in guiding the …

Natural History of Diabetic Coronary Atherosclerosis by Quantitative Measurement of Serial Coronary Computed Tomographic Angiography: Results of the PARADIGM Study

ObjectivesThis study aimed to determine the rate and extent of plaque progression (PP), changes in plaque features, and clinical predictors of PP in patients with diabetes mellitus (DM). BackgroundThe natural history of coronary PP in patients with DM is not well established. MethodsA total of 1,602 patients (age 61.3 ± 9.0 years; 60.3% men; median scan interval 3.8 years) who underwent serial coronary computed tomography angiography over a period of at least 24 months were enrolled and analyzed from the PARADIGM (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging) trial. Study endpoints were changes in plaque features in diabetics with PP and risk factors for PP by serial coronary computed tomography angiography between patients with and without DM. PP was defined if plaque volume at follow-up minus plaque volume at baseline was >0. ResultsDM was an independent risk factor for PP (84.6%; 276 of 326 patients with PP) in multivariate analysis (odds ratio [OR]: 1.526; 95% confidence interval [CI]: 1.100 to 2.118; p = 0.011). Independent risk factors for PP in patients with DM were male sex (OR: 1.485; 95% CI: 1.003 to 2.199; p = 0.048) and mean plaque burden at baseline ≥75% (OR: 3.121; 95% CI: 1.701 to 5.725; p ≤0.001). After propensity matching, percent changes in overall plaque volume (30.3 ± 36.9% in patients without DM and 36.0 ± 29.7% in those with DM; p = 0.032) and necrotic core volume (−7.0 ± 35.8% in patients without DM and 21.5 ± 90.5% in those with DM; p = 0.007) were significantly greater in those with DM. The frequency of spotty calcification, positive remodeling, and burden of low-attenuation plaque were significantly greater in patients with DM. ConclusionsPeople with DM experience greater PP, particularly significantly greater progression in adverse plaque, than those without DM. Male sex and mean plaque burden >75% at baseline were identified as independent risk factors for PP.

Impact of Non-obstructive left main disease on the progression of coronary artery disease: A PARADIGM substudy

BackgroundThe aim of the study is examine the impact of non-obstructive (<50%stenosis) left main (LM) disease on the natural history of coronary artery disease using serial coronary computed tomography angiography (CTA). MethodsCTAs from the PARADIGM (Progression of atherosclerotic plaque determined by computed tomographic angiography imaging) study, a prospective multinational registry of patients who underwent serial CTA at a ≥2 year interval were analyzed. Those without evidence of CAD on their baseline scan were excluded, as were those with obstructive left main disease. Coronary artery vessels and their branches underwent quantification of: plaque volume and composition; diameter stenosis; presence of high-risk plaque. ResultsOf 944 (62 ± 9 years, 60% male) who had evidence of CAD at baseline, 444 (47%) had LM disease. Those with LM disease had a higher baseline plaque volume (194.8 ± 221mm3 versus 72.9 ± 84.3mm3, p < 0.001) and a higher prevalence of high-risk plaque (17.5% versus 13%, p < 0.001) than those without LM disease. On multivariable general linear model, patients with LM disease had greater annual rates of progression of total (26.5 ± 31.4mm3/yr versus 14.9 ± 20.1mm3/yr, p < 0.001) and calcified plaque volume (17 ± 24mm3/yr versus 7 ± 11mm3/yr, p < 0.001), with no difference in fibrous, fibrofatty or necrotic core plaque components. ConclusionThe presence of non-obstructive LM disease is associated with greater rates of plaque progression and a higher prevalence of high-risk plaque throughout the entire coronary artery tree compared to CAD without LM involvement. Our data suggests that non-obstructive LM disease may be a marker for an aggressive phenotype of CAD that may benefit from more intensive treatment strategies.

Rationale and design of the Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography IMaging (PARADIGM) registry: A comprehensive exploration of plaque progression and its impact on clinical outcomes from a multicenter serial coronary computed tomographic angiography study

The natural history of coronary artery disease (CAD) in patients with low-to-intermediate risk is not well characterized. Although earlier invasive serial studies have documented the progression of atherosclerotic burden, most were focused on high-risk patients only. The PARADIGM registry is a large, prospective, multinational dynamic observational registry of patients undergoing serial coronary computed tomographic angiography (CCTA). The primary aim of PARADIGM is to characterize the natural history of CAD in relation to clinical and laboratory data. The PARADIGM registry (ClinicalTrials.govNCT02803411) comprises ≥2,000 consecutive patients across 9 cluster sites in 7 countries. PARADIGM sites were chosen on the basis of adequate CCTA volume, site CCTA proficiency, local demographic characteristics, and medical facilities to ensure a broad-based sample of patients. Patients referred for clinically indicated CCTA will be followed up and enrolled if they had a second CCTA scan. Patients will also be followed up beyond serial CCTA performance to identify adverse CAD events that include cardiac and noncardiac death, myocardial infarction, unstable angina, target vessel revascularization, and CAD-related hospitalization. The results derived from the PARADIGM registry are anticipated to add incremental insight into the changes in CCTA findings in accordance with the progression or regression of CAD that confer prognostic value beyond demographic and clinical characteristics.