Aims: The temporal instability of coronary atherosclerotic plaque preceding an incident acute coronary syndrome (ACS) is not well defined. We sought to examine differences in the volume and... Show moreAims: The temporal instability of coronary atherosclerotic plaque preceding an incident acute coronary syndrome (ACS) is not well defined. We sought to examine differences in the volume and composition of coronary atherosclerosis between patients experiencing an early (<= 90 days) versus late ACS (>90 days) after baseline coronary computed tomography angiography (CCTA). Methods and results: From a multicenter study, we enrolled patients who underwent a clinically indicated baseline CCTA and experienced ACS during follow-up. Separate core laboratories performed blinded adjudication of ACS events and quantification of CCTA including compositional plaque volumes by Hounsfield units (HU): calcified plaque >350 HU, fibrous plaque 131-350 HU, fibrofatty plaque 31-130 HU and necrotic core <30 HU. In 234 patients (mean age 62 +/- 12 years, 36% women), early and late ACS occurred in 129 and 105 patients after a mean of 395 +/- 622 days, respectively. Patients with early ACS had a greater maximal diameter stenosis and maximal cross-sectional plaque burden as compared to patients with late ACS (P < 0.05). Larger total, fibrous, fibrofatty, and necrotic core volumes were observed in the early ACS group (P < 0.05). Findings for total, fibrous, fibrofatty, and necrotic core volumes were reproduced in an external validation cohort (P < 0.05). Conclusions: Volumetric differences in composition of coronary atherosclerosis exist between ACS patients according to their timing antecedent to the acute event. These data support that a large burden of non-calcified plaque on CCTA is strongly associated with near-term plaque instability and ACS risk. Show less
BACKGROUND Among symptomatic patients, it remains unclear whether a coronary artery calcium (CAC) score alone is sufficient or misses a sizeable burden and progressive risk associated with... Show moreBACKGROUND Among symptomatic patients, it remains unclear whether a coronary artery calcium (CAC) score alone is sufficient or misses a sizeable burden and progressive risk associated with obstructive and nonobstructive atherosclerotic plaque.OBJECTIVES Among patients with low to high CAC scores, our aims were to quantify co-occurring obstructive and nonobstructive noncalcified plaque and serial progression of atherosclerotic plaque volume.METHODS A total of 698 symptomatic patients with suspected coronary artery disease (CAD) underwent serial coronary computed tomographic angiography (CTA) performed 3.5 to 4.0 years apart. Atherosclerotic plaque was quantified, including by compositional subgroups. Obstructive CAD was defined as >= 50% stenosis. Multivariate linear regression models were used to measure atherosclerotic plaque progression by CAC scores. Cox proportional hazard models estimated CAD event risk (median of 10.7 years of follow-up).RESULTS Across baseline CAC scores from 0 to >= 400, total plaque volume ranged from 30.4 to 522.4 mm(3) (P < 0.001) and the prevalence of obstructive CAD increased from 1.4% to 49.1% (P < 0.001). Of those with a 0 CAC score, 97.9% of total plaque was noncalcified. Among patients with baseline CAC <100, nonobstructive CAD was prevalent (40% and 89% in CAC scores of 0 and 1-99), with plaque largely being noncalcified. On the follow-up coronary CTA, volumetric plaque growth (P < 0.001) and the development of new or worsening stenosis (P < 0.001) occurred more among patients with baseline CAC >= 100. Progression varied compositionally by baseline CAC scores. Patients with no CAC had disproportionate growth in noncalcified plaque, and for every 1 mm(3) increase in calcified plaque, there was a 5.5 mm(3) increase in noncalcified plaque volume. By comparison, patients with CAC scores of >= 400 exhibited disproportionate growth in calcified plaque with a volumetric increase 15.7-fold that of noncalcified plaque. There was a graded increase in CAD event risk by the CAC with rates from 3.3% for no CAC to 21.9% for CAC >= 400 (P < 0.001).CONCLUSIONS CAC imperfectly characterizes atherosclerotic disease burden, but its subgroups exhibit pathogenic patterns of early to advanced disease progression and stratify long-term prognostic risk. (C) 2022 by the American College of Cardiology Foundation. Show less
Aims: Atherosclerosis develops progressively and worsens over time, yet event risk patterns vary in the left circumflex (LCx), right coronary artery (RCA) and left anterior descending (LAD). The... Show moreAims: Atherosclerosis develops progressively and worsens over time, yet event risk patterns vary in the left circumflex (LCx), right coronary artery (RCA) and left anterior descending (LAD). The aim of this analysis was to examine varying progressive disease alterations between the three major coronary arteries. Methods and results: Patients were included from a prospective, international registry of consecutive patients who underwent serial CCTA at a median interval of 3.3 years. Annual progression of quantitative total and compositional plaque volume were compared between the three coronary arteries (LCx, LAD, and RCA). Other analyses compared stenosis >= 50% and new high-risk plaque (HRP; >= 2 of the following: spotty calcification, positive remodelling, napkin-ring sign, and low-attenuation plaque) on follow-up. Generalized estimating equations and marginal Cox regression models were used to compare progression, with covariate adjustment by the baseline atherosclerotic cardiovascular disease risk score, statin use, and plaque burden. Quantitative plaque measurements were calculated in 1344 patients (age 60 +/- 9 years, 57% men). Plaque progression occurred less often in the LCx (41.0%) as compared to the RCA (52.7%) and LAD (77.4%, P < 0.001). Odds for annual plaque burden increase >= population mean were 1.98- and 1.43-fold as high in the LAD (P < 0.001) and RCA (P < 0.001) as compared to the LCx. Similarly, the LAD was associated with a 2.45 higher risk of progression to obstructive CAD (P < 0.001), as compared to the LCx; with no differences between the RCA and LCx (P = 0.13). New HRP lesions formed least often in the LCx (3.4%), followed by the RCA (8.1%) and most often in the LAD (10.1%; P < 0.001). Conclusions: Our findings reveal novel insights into varied patterns of atherosclerotic plaque progression within the LCx as compared to the other epicardial coronary arteries. These varied patterns reflect differing stages in the disease process or differing pathogenic milieu across the coronary arteries. Show less
Aims: The relationship between AtheroSclerotic CardioVascular Disease (ASCVD) risk and vessel-specific plaque evaluation using coronary computed tomography angiography (CCTA), focusing on plaque... Show moreAims: The relationship between AtheroSclerotic CardioVascular Disease (ASCVD) risk and vessel-specific plaque evaluation using coronary computed tomography angiography (CCTA), focusing on plaque extent and composition, has not been examined. To evaluate differences in quantified plaque characteristics (using CCTA) between the three major coronary arteries [left anterior descending (LAD), right coronary (RCA), and left circumflex (LCx)] among subgroups of patients with varying ASCVD risk.Methods and results: Patients were included from a prospective, international registry of consecutive patients who underwent CCTA for evaluation of coronary artery disease. ASCVD risk groups were <7.5% (low), 7.5-20% (intermediate), and ≥20% (high). Among the ASCVD risk groups, the three coronary arteries were compared regarding quantified plaque volume and composition. Whole-heart plaque quantification was performed in 1340 patients (age 60 ± 9 years, 58% men). Across low, intermediate, and high ASCVD risk patients, the volume of plaque increased proportionally but was least in the LCx (7.4, 9.0, and 25.3 mm3, respectively) as compared with the RCA (19.3, 32.6, and 67.0 mm3, respectively, all P ≤ 0.006) and LAD (39.9, 60.8, and 93.3 mm3, respectively, all P < 0.001). In each ASCVD risk group, the composition of plaque in the LCx exhibited the least necrotic core and fibrofatty plaque (P < 0.05 vs. LAD and RCA).Conclusion: Among patients with varying risk of ASCVD, plaque in the LCx is decidedly less and is comprised of less non-calcified plaque supporting prior evidence of the lower rates of acute coronary events in this vessel. 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
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
