Percent Atheroma Volume Research Articles

Coronary artery echo-attenuated plaques in acute coronary syndromes: a serial intravascular ultrasound imaging study

Abstract Background Echo attenuation of atherosclerotic plaque (EAP) identified with intravascular ultrasound (IVUS) has been shown to correlate with vulnerable plaque morphologies and their presence is predictive of future cardiovascular events. EAP have predominantly been assessed at a single time point and their natural history in the immediate post acute coronary syndrome (ACS) period remains unknown. We aimed to assess this and whether their presence correlated with a more modifiable plaque composition in the immediate post-ACS setting. Methods Serial IVUS imaging was performed in non-culprit vessels of 270 patients undergoing angiogram for ACS and at 3 month follow up. IVUS analysis of plaque burden and EAP was performed. Results Baseline characteristics are described in Table 1. EAP were present at baseline in 62 patients (23%) with these patients more likely to be male (89.1% vs. 76.7%, p=0.03) but no differences in other atherosclerotic risk factors. There was no difference in baseline plaque burden between patients with EAP and those without (Percent atheroma volume [PAV] 38.9% vs. 37.8%, p=0.32). At follow up IVUS change in PAV was not statistically significantly different between patients with baseline EAP and those without (ΔPAV 0.09% vs. −0.36%, p=0.43), and neither was there a difference in the frequency of plaque regressors (42.7% vs 50%, p=0.31). EAP had resolved in 25 patients (40%) within 3 months at the follow up IVUS. Despite contemporary post-ACS therapy 18 patients who had not had EAP present at baseline (9%) developed new EAP at the follow up IVUS. Conclusion EAP were present in a quarter of ACS patients and were not associated with baseline plaque burden or a more modifiable plaque phenotype. In the setting of contemporary ACS treatments the natural history of high risk IVUS plaque characteristics such as EAP is dynamic with significant change even over a 3 month period in the post ACS setting. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Royal Adelaide Hospital Research Fund AR Clarkson Scholarship

High-risk plaque regression after intensive dietary intervention in patients with non-obstructive coronary artery disease: a randomised computed tomography angiography study (DISCO-CT)

Abstract Background Lifestyle and diet modification are the forefront in the management of coronary artery disease (CAD), however, there is no data whether they may stop progression of atheroslcerosis. Some coronary plaque characteristics are known to increase the risk of future cardiovascular events independently of coronary stenosis severity. These plaques are characterized by the presence of lipids and necrotic elements, and can be identified with coronary computed tomography angiography (CTA). Purpose To study the effect of intensive dietary intervention on changes in atherosclerotic plaque volume and composition. Methods We enrolled 89 patients (41% women, mean age 60±7.7 years) with nonobstructive coronary lesions (<70% stenosis) identified by CTA (2x192-multislice scanner, temporal resolution 66 ms), qualified to medical treatment. All participants were subjected to optimal medical therapy (OMT). Patients were randomised (1:1) to either A) OMT with regular follow-up (after 1, 3, 6, 9 and 12 months) by a dietitian to stick to Dietary Approaches to Stop Hypertension (DASH) model, or B) routine management, ie. OMT alone. CTA was repeated in all patients after the mean time of 66.9±13.7 weeks. An experienced observer blinded to the allocated treatment group and other clinical data evaluated all of the scans. The outcome was change in total plaque volume, percent plaque volume and plaque composition, assessed with a dedicated software system. Based on tissue attenuation ranges in Hounsfield units (HU), the following components of atheroma were distinguished: dense calcium (>351 HU), fibrous plaque (151 to 350 HU), and fibrofatty plaque plus necrotic core (−100 to 150 HU), regarded as the vulnerable plaque component. Results Total plaque volume did not change significantly in any group (p=0.41; Figure 1A). Percent atheroma volume increased in the control arm vs. no significant change in the experimental arm, with no significant intergroup difference (p=0.79; Figure 1B). Vulnerable plaque component decreased in both subgroups, by 52.9±82.2 mm3 in the experimental vs. 20.8±58.5 mm3 in the control arm, and there was a significant difference in the reductions between the groups (p=0.04; Figure 1C). Fibrous plaque volume and dense calcium volume did not change significantly in any group (+9.5±117.8 mm3 in the experimental vs. +7.6±92.1 mm3 in the control arm, p=0.93, and +33±68.9 mm3 vs. +30.2±52.5 mm3, p=0.78, respectively). Conclusions Intensive diet intervention atop OMT can stop the progression of atherosclerosis and lead to a significant reduction in vulnerable plaque component compared to OMT alone. Figure 1 Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Institute of Cardiology in Warsaw, Poland

Sex-specific risk for ischemia by invasive fractional flow reserve according to coronary atherosclerotic features: results from the CREDENCE trial

Abstract Background Evolving evidence suggests unique sex-specific mechanisms underlying coronary artery disease (CAD). However, it remains unknown if certain coronary atherosclerotic features confer a higher risk for ischemia in women versus men. Purpose To determine the association between coronary atherosclerotic features on coronary computed tomography angiography (CCTA) and ischemia by invasive fractional flow reserve (FFR) in women versus men. Methods Secondary analysis of the CREDENCE trial, including patients referred for nonemergent invasive coronary angiography (ICA). All patients underwent CCTA with semi-automatic quantification of coronary atherosclerosis, as well as ICA with FFR interrogation of all major epicardial arteries ≥2 mm. Generalized estimating equations were calculated to assess the association between coronary atherosclerotic features and invasive vessel-specific ischemia (FFR ≤0.80). Sex interactions were tested, adjusted for age. Results From 612 patients (mean age 64±10 years, 30% women) with 1,686 analyzed vessels, a total of 436 (26%) vessels were ischemic. Women were significantly older than men (p<0.001), but with similar distribution of risk factors and medication usage (p≥0.09). In both women and men, all general and compositional features of coronary atherosclerosis were significantly associated with ischemia. However, tests for interaction (Figure 1) revealed higher relative odds for ischemia among women as compared to men for total percent atheroma volume ([PAV], p=0.006), the number of lesions with high-risk plaque (p=0.027), the number of lesions with >30% stenosis (p=0.030), noncalcified PAV <130 HU and <350 HU (p≤0.003), and calcified PAV (p=0.007). Conclusion Our results support a prominent influence of coronary atherosclerotic features that uniquely impact ischemic risk among women more so than men. These data support the role of CCTA for providing valuable information to guide management of symptomatic women. Figure 1. Ischemic risk in women vs. men Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Institutes of Health - National Heart, Lung, and Blood Institute

Effect of plaque characteristics on ischemia by invasive fractional flow reserve in nonobstructive versus obstructive coronary artery disease: results from the CREDENCE trial

Abstract Background Mismatches between the severity of coronary stenosis and the presence of ischemia by invasive fractional flow reserve (FFR) are frequently reported. Purpose To investigate whether plaque characteristics as evaluated with coronary computed tomography angiography (CCTA) may explain this discordance in nonobstructive versus obstructive coronary artery disease (CAD). Methods From the CREDENCE trial, 612 patients with suspected CAD at 13 sites (64±10 years, 70% men) underwent CCTA with semi-automated whole heart quantification and invasive coronary angiography with 3-vessel FFR measurements. Obstructive CAD was visually defined as ≥50% stenosis. The primary endpoint of coronary vessel-specific ischemia was defined as FFR ≤0.80. Generalized estimating equations were calculated to evaluate the effect of plaque characteristics on coronary vessel-specific ischemia. Interactions were tested by obstructive CAD, adjusted for age. Results Among 1,686 vessels, ischemia was present in 436 (26%) vessels. In both nonobstructive and obstructive CAD, the majority of plaque characteristics were associated with coronary vessel-specific ischemia (p≤0.005, Figure 1). In nonobstructive CAD, odds for ischemia were significantly higher for total percent atheroma volume (PAV, p<0.001), calcified PAV (p<0.001), noncalcified PAV <350 and <130 HU (p≤0.043), the number of lesions at a bifurcation (p=0.009) and the number of lesions with high-risk plaque (HRP, p=0.033) when compared with obstructive CAD. Conclusion Our findings reveal that ischemia by FFR is documented in the setting of both nonobstructive and obstructive CAD on CCTA. Detection of atherosclerotic plaque characteristics associated with ischemia can potentially improve diagnostic certainty and guide management of symptomatic patients with nonobstructive CAD. Figure 1. Odds ratios for ischemia. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Institutes of Health - National Heart, Lung, and Blood Institute

Relationship between arterial remodelling and serial changes in coronary atherosclerosis by intravascular ultrasound: an analysis of the IBIS-4 study.

Arterial remodelling is an important determinant of coronary atherosclerosis. Assessment of the remodelling index, comparing a lesion to a local reference site, is a suboptimal correlate of serial vascular changes. We assessed a novel approach which, unlike the local-reference approach, uses the entire artery's global remodelling as reference. Serial (baseline and 13 months) intravascular ultrasound was performed in 146 non-infarct-related arteries of 82 patients treated with high-intensity statin. Arteries were divided into 3-mm segments (n = 1479), and focal remodelling was characterized in individual segments at both timepoints applying the global arterial reference approach. First, we compared preceding vascular changes in relation to follow-up remodelling. Second, we examined whether baseline remodelling predicts subsequent plaque progression/regression. At follow-up, segments with constrictive vs. compensatory or expansive remodelling had greater preceding reduction of vessel area (-0.67 vs. -0.38 vs. -0.002mm2; P < 0.001) and lumen area (-0.82 vs. -0.09 vs. 0.40mm2; P < 0.001). Overall, we found significant regression in percent atheroma volume (PAV) [-0.80% (-1.41 to -0.19)]. Segments with constrictive remodelling at baseline had greater subsequent PAV regression vs. modest regression in the compensatory, and PAV progression in the expansive remodelling group (-6.14% vs. -0.71% vs. 2.26%; P < 0.001). Lesion-level analyses (n = 118) showed no differences when remodelling was defined by the local reference approach at baseline or follow-up. Remodelling assessment using a global arterial reference approach, but not the commonly used, local reference site approach, correlated reasonably well with serial changes in arterial dimensions and identified arterial segments with subsequent PAV progression despite intensive statin treatment and overall atheroma regression.

C-reactive protein levels and plaque regression with evolocumab: Insights from GLAGOV

ObjectiveOn-treatment levels of high sensitivity C-reactive protein (hsCRP) in statin-treated patients predict plaque progression and the prospective risk of atherosclerotic cardiovascular events. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors produce additional LDL-C lowering, reduce plaque burden and improve cardiovascular outcomes in statin-treated patients. It is unknown whether residual systemic inflammation attenuates their favorable effects on plaque burden. MethodsGLAGOV compared the effects of treatment for 78 weeks with evolocumab or placebo on progression of coronary atherosclerosis in statin-treated patients with coronary artery disease.Clinical demographics, biochemistry and changes in both the burden (percentage atheroma volume (PAV), total atheroma volume (TAV), n ​= ​413) and composition (n ​= ​162) of coronary plaque were evaluated in evolocumab-treated patients according to baseline hsCRP strata (<1, 1–3, >3 ​mg/L). ResultsThe study cohort comprised 413 evolocumab-treated patients (32% low [<1 ​mg/L], 41% intermediate [1–3 ​mg/L] and 27% high [>3 ​mg/L] baseline hsCRP levels). Patients in the highest hsCRP stratum were more likely to be female and had a higher prevalence of diabetes, hypertension, and the metabolic syndrome. LDL-C levels were similar across the groups, however participants with higher hsCRP levels had higher triglyceride and lower HDL-C levels at baseline. At follow-up, the change in PAV from baseline (−0.87% [low] vs. −0.84% [intermediate] vs. −1.22% [high], p ​= ​0.46) and the proportion of patients experiencing any degree of regression (65.9% vs. 63.5% vs. 63.1%, p ​= ​0.88) was similar across hsCRP strata and when evaluated by levels of achieved LDL-C. There were no serial differences in plaque composition by hsCRP strata. ConclusionThe ability of evolocumab to induce regression in statin-treated patients is not attenuated by the presence of enhanced systemic inflammation. This underscores the potential benefits of intensive lipid lowering, even in the presence of heightened inflammatory states.

Effect of evolocumab on the progression and stability of atherosclerotic plaques as evaluated by grayscale and iMAP-IVUS.

Evolocumab inhibits the proprotein convertase subtilisin/kexin type 9 protein and is a potent cholesterol-lowering drug. However, the relationship between evolocumab and inflammation, and the effects of evolocumab on the stability of atherosclerotic plaques remain unknown. Twenty-seven purebred New Zealand rabbits were fed with an atherogenic diet for 2 weeks. The abdominal aortic endothelium was balloon-injured. The rabbits were divided into the atorvastatin (2 mg/kg/day; Ato), evolocumab (7 mg/kg/2 weeks, Evo) and control groups. Intravascular ultrasound (IVUS) images of the abdominal artery were analyzed at 10 and 18 weeks. Additionally, the serum levels of the biomarkers were measured at baseline, and at 10 and 18 weeks. The serum levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and monocyte chemoattractant protein-1 (MCP-1) increased after 10 weeks of administration of the proatherosclerotic diet, while the levels of high-density lipoprotein cholesterol (HDL-C) and transforming growth factor-β (TGF-β) decreased. The reduction in the serum levels of triglycerides, total cholesterol, LDL-C, MCP-1, TGF-β, and toll-like receptor 4 (TLR4) following treatment with evolocumab was higher than that of atorvastatin. Both evolocumab and atorvastatin reduced the percent atheroma volume. Evolocumab increased the fibrotic% and decreased the necrotic%. Correlation analysis revealed that the levels of triglycerides, total cholesterol, LDL-C, MCP-1, TGF-β, and TLR4 were negatively correlated with the fibrotic%, but were positively correlated with the necrotic%. Multivariate linear regression analysis revealed that treatment with atorvastatin, and especially evolocumab, was a consistent predictor of the percent atheroma volume, and fibrotic and necrotic composition. Proprotein convertase subtilisin/kexin type 9 regulates the serum levels of lipid and cholesterol may via inflammatory pathways. The results also indicate that evolocumab is more potent than atorvastatin in suppressing the progression and stability of atherosclerotic plaque in rabbits.

Oral Calcium Supplements Associate With Serial Coronary Calcification: Insights From Intravascular Ultrasound

ObjectivesThis study sought to evaluate and assess the extent of serial coronary artery calcification in response to oral calcium supplementation. BackgroundOral calcium supplements are frequently used despite their cardiovascular safety remaining controversial. Their effects on serial coronary calcification are not well established. MethodsIn a post hoc patient-level analysis of 9 prospective randomized trials using serial coronary intravascular ultrasound, changes in serial percentage of atheroma volume (PAV) and calcium indices (CaI) were compared in matched segments of patients coronary artery disease who were receiving concomitant calcium supplements (n = 447) and in those who did not receive supplements (n = 4,700) during an 18- to 24-month trial period. ResultsPatients (mean age 58 ± 9 years; 73% were men; 43% received concomitant high-intensity statins) demonstrated overall annualized changes in PAV and CaI with a mean of −0.02 ± 1.9% (p = 0.44) and a median of 0.02 (interquartile range: 0.00 to 0.06) (p < 0.001) from baseline, respectively. Following propensity-weighted mixed modeling adjusting for treatment and a range of demographic, clinical, ultrasonic, and laboratory parameters (including but not limited to sex, race, baseline, and annualized change in PAV, baseline CaI, concomitant high-intensity statins, diabetes mellitus, renal function), there were no significant between-group differences in annualized changes in PAV (least-squares mean: 0.09; 95% confidence interval [CI]: −0.20 to 0.37 vs. 0.01; 95% CI: −0.27 to 0.29; p = 0.092) according to calcium supplement intake. Per a multivariable logistic regression model accounting for the range of covariates described, calcium supplementation independently associated with an increase in annualized CaI (odds ratio: 1.15; 95% CI: 1.05 to 1.26; p = 0.004). ConclusionsOral calcium supplementation may increase calcium deposition in the coronary vasculature independent of changes in atheroma volume. The impact of these changes on plaque stability and cardiovascular outcomes requires further investigation.

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

Effects of Statin Plus Ezetimibe on Coronary Plaques in Acute Coronary Syndrome Patients with Diabetes Mellitus: Sub-Analysis of PRECISE-IVUS Trial.

Aim: Coronary plaque regression is weak in acute coronary syndrome (ACS) patients with diabetes mellitus (DM). We evaluated whether dual lipid-lowering therapy (DLLT) with ezetimibe and atorvastatin attenuates coronary plaques in ACS patients with DM.Methods: The prospective, randomized controlled, multicenter PRECISE-IVUS (Plaque Regression with Cholesterol Absorption Inhibitor or Synthesis Inhibitor Evaluated by Intravascular Ultrasound) trial assigned 246 patients undergoing percutaneous coronary intervention to DLLT or atorvastatin monotherapy and evaluated IVUS-derived changes in percent atheroma volume (ΔPAV), at baseline and 9–12-month follow-up, in 126 ACS cases, including 25 DM patients. The atorvastatin dose was up-titrated to achieve low-density lipoprotein cholesterol (LDL-C) < 70 mg/dL.Results: In DM patients, the monotherapy group (n = 13) and the DLLT group (n = 12) showed a similar prevalence of coronary risks and baseline lipid profiles. During the study, the change in LDL-C level was similar between DM and non-DM patients. Compared with non-DM patients, DM patients showed weaker regression of ΔPAV by DLLT than those who underwent monotherapy (DM: −2.77 ± 3.47% vs. −0.77 ± 2.51%, P = 0.11; non-DM: −2.01 ± 3.36% vs. −0.08 ± 2.66%, P = 0.008). The change in LDL-C level was not correlated with ΔPAV in non-DM patients, but there was significant correlation between the change in LDL-C level and ΔPAV in DM patients (r = 0.52, P = 0.008).Conclusions: ACS patients with DM showed weaker coronary plaque regression than their counterparts. A significant correlation between the change in LDL-C level and ΔPAV in DM patients suggested that more intensive lipid-lowering therapy is required in ACS patients with DM.

Comparative effectiveness of coronary artery stenosis and atherosclerotic plaque burden assessment for predicting 30-day revascularization and 2-year major adverse cardiac events

To provide comparative prognostic information of coronary atherosclerotic plaque volume and stenosis assessment in patients with suspected coronary artery disease (CAD). We followed 372 patients with suspected or known CAD enrolled in the CORE320 study for 2 years after baseline 320-detector row cardiac CT scanning and invasive quantitative coronary angiography (QCA). CT images were analyzed for coronary calcium scanning (CACS), semi-automatically derived total percent atheroma volume (PAV), segment stenosis score (SSS), in addition to traditional stenosis assessment (≥ 50%) by CT and QCA for (1) 30-day revascularization and (2) major adverse cardiac events (MACE). Area under the receiver operating characteristic curve (AUC) was used to compare accuracy of risk prediction. Sixty percent of patients had obstructive CAD by QCA with 23% undergoing 30-day revascularization and 9% experiencing MACE at 2 years. Most late events (20/32) were revascularization procedures. Prediction of 30-day revascularization was modest (AUC range 0.67-0.78) but improved after excluding patients with known CAD (AUC range 0.73-0.86, p < 0.05 for all). Similarly, prediction of MACE improved after excluding patients with known CAD (AUC range 0.58-0.73 vs. 0.63-0.77). CT metrics of atherosclerosis burden performed overall similarly but stenosis assessment was superior for predicting 30-day revascularization. Angiographic and coronary atherosclerotic plaque metrics perform only modestly well for predicting 30-day revascularization and 2-year MACE in high risk patients but improve after excluding patients with known CAD. Atherosclerotic plaque metrics did not yield incremental value over stenosis assessment for predicting events that predominantly consisted of revascularization procedures. NCT00934037.

Progression of ultrasound plaque attenuation and low echogenicity associates with major adverse cardiovascular events.

Intravascular ultrasound (IVUS) imaging can visualize vulnerable plaque features including attenuation (AP) and echolucency (ELP). While IVUS-derived vulnerable plaque features associate with microvascular obstruction during percutaneous coronary intervention, the relationship between these plaque features and clinical outcomes has not been established. This analysis aimed to evaluate the association of AP/ELP with cardiovascular events. Serial IVUS imaging was reviewed in 1497 patients, followed for 18-24 months, with coronary artery disease from two clinical trials. Attenuated plaque and ELP were identified to measure each characteristics (AP arc, ELP area, and lengths), which permitted calculation of an AP index (API) and ELP volume. Attenuated plaque/ELP progression was defined as patients with any increase of API or ELP volume on serial imaging. The major cardiovascular events (MACEs) were defined as death, myocardial infarction, stroke, and coronary revascularization. AP or ELP was identified in 282 patients (18.8%) at baseline and 160 (10.7%) patients demonstrated an increase in AP or ELP at follow-up. The incidence of MACE was higher in patients with baseline AP/ELP than those without (8.2% vs. 3.9%, P = 0.002). Patients with AP/ELP progression were more likely to be acute coronary syndrome (41.9 vs. 33.2%, P = 0.03) and have greater baseline percent atheroma volume (40.0% vs. 35.8%, P < 0.001) than those without. On multivariable analysis, AP/ELP progression was more strongly associated with MACE [baseline AP/ELP: hazard ratio (HR) 1.76, 95% confidence interval (CI) 1.05-2.97, AP/ELP progression: HR 2.19, 95% CI 1.24-3.86]. Attenuation/ELP progression was associated with a higher prevalence of cardiovascular events, supporting a potential role for the identification of high-risk vulnerable plaques in patients with coronary artery disease.

Sitagliptin attenuates the progression of coronary atherosclerosis in patients with coronary disease and type 2 diabetes

Background and aimsType 2 diabetes mellitus (T2DM) is a well-recognized independent risk factor for ASCVD, the aim of this study was to investigate the effects of a dipeptidyl peptidase-4 inhibitor, sitagliptin, on prevention of progression of coronary atherosclerosis assessed by three-dimensional quantitative coronary angiography (3D-QCA) in T2DM patients with coronary artery disease (CAD). MethodsThis was a prospective, randomized, double-center, open-label, blinded end point, controlled 18-month study in patients with CAD and T2DM. A total of 149 patients, who had at least 1 atherosclerotic plaque with 20%–80% luminal narrowing in a coronary artery, and had not undergone intervention during a clinically indicated coronary angiography or percutaneous coronary intervention, were randomized to sitagliptin group (n = 74) or control group (n = 75). Atherosclerosis progression was measured by repeat 3D-QCA examination in 88 patients at study completion. The primary outcome was changes in percent atheroma volume (PAV) from baseline to study completion measured by 3D-QCA. Secondary outcomes included change in 3D-QCA-derived total atheroma volume (TAV) and late lumen loss (LLL). ResultsThe primary outcome of PAV increased of 1.69% (95%CL, −0.8%–4.2%) with sitagliptin and 5.12% (95%CL, 3.49%–6.74%) with the conventional treatment (p = 0.023). The secondary outcome of change in TAV in patients treated with sitagliptin increased of 6.45 mm3 (95%CL,-2.46 to 6.36 mm3) and 9.45 mm3 (95%CL,-4.52 to 10.14 mm3) with conventional treatment (p = 0.023), however, no significant difference between groups was observed (p = 0.175). Patients treated with sitagliptin had similar LLL as compared with conventional antidiabetics (−0.06, 95%CL, −0.22 to 0.03 vs. −0.08, −0.23 to −0.03 mm, p = 0.689). ConclusionsIn patients with type 2 diabetes and coronary artery disease, treatment with sitagliptin resulted in a significantly lower rate of progression of coronary atherosclerosis compared with conventional treatment.

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.

Percent atheroma volume: Optimal variable to report whole-heart atherosclerotic plaque burden with coronary CTA, the PARADIGM study

Background and aimsDifferent 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. MethodsThe 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 mm3, (2) percent atheroma volume (PAV) in % [which equaled: PV/vessel volume * 100%], and (3) normalized total atheroma volume (TAVnorm) in mm3 [which equaled: PV/vessel length * mean population vessel length]. Only data from the baseline CCTA were used. PV, PAV, and TAVnorm 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. ResultsThe 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 TAVnorm, but similar PAV. The relation between larger BSA and larger absolute plaque volume (PV and TAVnorm) 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 TAVnorm (P = 0.003), but not with PAV (P = 0.201). The three plaque burden methods were equally affected by sex. ConclusionsPAV was less affected by patient's body surface area then PV and TAVnorm and may be the preferred method to report coronary atherosclerotic burden.

In vivo relationship between near-infrared spectroscopy-detected lipid-rich plaques and morphological plaque characteristics by optical coherence tomography and intravascular ultrasound: a multimodality intravascular imaging study.

We assessed morphological features of near-infrared spectroscopy (NIRS)-detected lipid-rich plaques (LRPs) by using optical coherence tomography (OCT) and intravascular ultrasound (IVUS). IVUS-NIRS and OCT were performed in the two non-infarct-related arteries (non-IRAs) in patients undergoing percutaneous coronary intervention for treatment of an acute coronary syndrome. A lesion was defined as the 4 mm segment with the maximum amount of lipid core burden index (maxLCBI4mm) of each LRP detected by NIRS. We divided the lesions into three groups based on the maxLCBI4mm value: <250, 250-399, and ≥400. OCT analysis and IVUS analysis were performed blinded for NIRS. We measured fibrous cap thickness (FCT) by using a semi-automated method. A total of 104 patients underwent multimodality imaging of 209 non-IRAs. NIRS detected 299 LRPs. Of those, 41% showed a maxLCBI4mm <250, 39% a maxLCBI4mm 251-399, and 19% a maxLCBI4mm ≥400. LRPs with a maxLCBI4mm ≥400, as compared with LRPs with a maxLCBI4mm 250-399 and <250, were more frequently thin-cap fibroatheroma (TCFA) (42.1% vs. 5.1% and 0.8%; P < 0.001) with a smaller minimum FCT (80 μm vs. 110 μm and 120 μm; P < 0.001); a higher IVUS-derived percent atheroma volume (53% vs. 53% and 44%; P < 0.001) and a higher remodelling index (1.08 vs. 1.02 and 1.01; P < 0.001). MaxLCBI4mm correlated with OCT-derived FCT (r = 0.404; P < 0.001) and was the best predictor for TCFA with an optimal cut-off value of 401 (area under the curve = 0.882; P < 0.001). LRPs with increasing maxLCBI4mm exhibit OCT and IVUS features of presumed plaque vulnerability including TCFA morphology, increased plaque burden, and positive remodelling.

Remnant cholesterol, coronary atheroma progression and clinical events in statin-treated patients with coronary artery disease.

Remnant cholesterol has been proposed to promote atherosclerotic cardiovascular disease independent of low-density lipoprotein cholesterol, yet the underlying mechanisms are not well understood. We aimed to study the association of remnant cholesterol with coronary atheroma progression and clinical events. We analyzed data from 5754 patients with coronary artery disease undergoing serial intravascular ultrasonography who were enrolled in 10 trials examining various medical therapies. Remnant cholesterol was calculated as (non-high-density lipoprotein cholesterol - low-density lipoprotein cholesterol (estimated using the Hopkins-Martin equation)). Changes in percentage atheroma volume and 2-year major adverse cardiovascular events were compared across various levels of remnant cholesterol, and multivariable models were used to assess the independent relationship of remnant cholesterol with changes in percentage atheroma volume. The mean age was 58.1 ± 9.2 years, 28% were women and 96% received a statin. Percentage atheroma volume progression (changes in percentage atheroma volume > 0) occurred in a linear fashion at on-treatment remnant cholesterol levels of 25 mg/dL or greater. The highest on-treatment remnant cholesterol quartile demonstrated greater percentage atheroma volume progression (+0.53 ± 0.26 vs. -0.15 ± 0.25%, P < 0.001) and 2-year major adverse cardiovascular events (23% vs. 14%, log-rank P < 0.001) compared with the lowest. In multivariable analyses, changes in percentage atheroma volume significantly correlated with on-treatment remnant cholesterol (P < 0.001] independent of low-density lipoprotein cholesterol, apolipoprotein B, C-reactive protein, high-density lipoprotein cholesterol levels and clinical risk factors. Changes in percentage atheroma volume also significantly correlated with changes in remnant cholesterol following multivariable adjustment. In statin-treated patients with atherosclerotic cardiovascular disease, remnant cholesterol was associated with coronary atheroma progression regardless of conventional lipid parameters, C-reactive protein or clinical risk factors. Higher remnant cholesterol levels also correlated with higher major adverse cardiovascular events. These data support further investigations into remnant cholesterol-lowering interventions in statin-treated patients harboring residual atherosclerotic cardiovascular disease risk.

Differences in Progression to Obstructive Lesions per High-Risk Plaque Features and Plaque Volumes With CCTA

ObjectivesThis study explored whether the pattern of nonobstructive lesion progression into obstructive lesions would differ according to the presence of high-risk plaque (HRP). BackgroundIt is still debatable whether HRP simply represents a certain phase during the natural history of coronary atherosclerotic plaques or if disease progression would differ according to the presence of HRP. MethodsPatients with nonobstructive coronary artery disease, defined as percent diameter stenosis (%DS) <50%, were enrolled from a prospective, multinational registry of consecutive patients who underwent serial coronary computed tomography angiography at an interscan interval of ≥2 years. HRP was defined as lesions with ≥2 features of positive remodeling, spotty calcification, or low-attenuation plaque. Quantitative total and compositional percent atheroma volume (PAV) at baseline and annualized PAV change were compared between non-HRP and HRP lesions. ResultsA total of 3,049 nonobstructive lesions were identified from 1,297 patients (mean age 60.3 ± 9.3 years; 56.8% men). There were 2,624 non-HRP and 425 HRP lesions. HRP lesions had a greater total PAV and all noncalcified components of PAV and %DS at baseline compared with non-HRP lesions. However, the annualized total PAV changes were greater in non-HRP lesions than in HRP lesions. On multivariate analysis adjusted for clinical risk factors, drug use, change in lipid level, total PAV, %DS, and HRP, only the baseline total PAV and %DS independently predicted the development of obstructive lesions (hazard ratio [HR]: 1.04; 95% confidence interval [CI]: 1.02 to 1.07, and HR: 1.07; 95% CI: 1.04 to 1.10, respectively, all p < 0.05), whereas the presence of HRP did not (p > 0.05). ConclusionsThe pattern of individual coronary atherosclerotic plaque progression differed according to the presence of HRP. Baseline PAV, not the presence of HRP features, was the most important predictor of lesions developing into obstructive lesions. (Progression of Atherosclerotic Plaque Determined By Computed Tomographic Angiography Imaging [PARADIGM]; NCT02803411)

P6162Difference in progression to obstructive lesions according to the presence of high-risk plaque features

Abstract Background It is still debatable whether the so-called high-risk plaque (HRP) simply represents a certain phase during the natural history of coronary atherosclerotic plaques or the disease progression would differ according to the presence of HRP. Purpose We determined whether the pattern of non-obstructive lesion progression into obstructive lesions would differ according to the presence of HRP. Methods Patients with non-obstructive coronary artery disease, defined as % diameter stenosis (%DS) ≥50%, were enrolled from a prospective, multinational registry of consecutive patients who underwent serial coronary computed tomography angiography at an inter-scan interval of ≥2 years. HRP was defined as lesions with ≥2 of positive remodelling, spotty calcification, and low-attenuation plaque. The total and compositional percent atheroma volume (PAV) at baseline and annualized PAV change were compared between non-HRP and HRP lesions. Results A total of 1,115 non-obstructive lesions were identified from 327 patients (61.1±8.9 years old, 66.0% male). There were 690 non-HRP and 425 HRP lesions. HRP lesions possessed greater PAV and %DS at baseline compared to non-HRP lesions. However, the annualized total and non-calcified PAV change were greater in non-HRP lesions than in HRP lesions. On multivariate analysis, addition of baseline PAV and %DS to clinical risk factors improved the predictive power of the model (Table). When clinical risk factors, PAV, %DS, and HRP were all adjusted on Model 3, only baseline PAV and %DS independently predicted the development of obstructive lesions (hazard ratio (HR) 1.046 [95% confidence interval (CI): 1.026–1.066] and HR 1.087 [95% CI: 1.055–1.119], respectively, all p&lt;0.001), while HRP did not (p&gt;0.05). Comparison of C-statistics of per-lesion analysis to predict progression to obstructive lesion C-statistics (95% CI) P Model 1: Baseline PAV 0.880 (0.879–0.884) – Model 2: Model 1 + baseline %DS 0.938 (0.937–0.939) vs. Model 1: &lt;0.001 Model 3: Model 2 + HRP 0.935 (0.934–0.937) vs. Model 2: 0.004 Adjusted for age, male sex, hypertension, diabetes mellitus, hyperlipidemia, family history of coronary artery disease, smoking, body mass index, and statin use. Conclusion The pattern of individual coronary atherosclerotic plaque progression differed according to the presence of HRP. Baseline PAV was the most important predictor for lesions developing into obstructive lesions rather than the presence of HRP features at baseline. Acknowledgement/Funding This work was supported by the National Research Foundation of Korea funded by the Ministry of Science and ICT (Grant No. 2012027176).