Early versus late acute coronary syndrome risk patterns of coronary atherosclerotic plaque.

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 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.

Relationship Between Coronary Artery Calcium and Atherosclerosis Progression Among Patients With Suspected Coronary Artery Disease.

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 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 mm3 (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 mm3 increase in calcified plaque, there was a 5.5 mm3 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.

Comparative differences in the atherosclerotic disease burden between the epicardial coronary arteries: quantitative plaque analysis on coronary computed tomography angiography.

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 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 mm3), followed by the RCA (32.8 ± 82.7 mm3; P < 0.001), and LAD (58.6 ± 83.3 mm3; 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.

Age- and sex-related features of atherosclerosis from coronary computed tomography angiography in patients prior to acute coronary syndrome: results from the ICONIC study.

AIMS: Although there is increasing evidence supporting coronary atherosclerosis evaluation by coronary computed tomography angiography (CCTA), no data are available on age and sex differences for quantitative plaque features. The aim of this study was to investigate sex and age differences in both qualitative and quantitative atherosclerotic features from CCTA prior to acute coronary syndrome (ACS). METHODS AND RESULTS: Within the ICONIC study, in which 234 patients with subsequent ACS were propensity matched 1:1 with 234 non-event controls, our current subanalysis included only the ACS cases. Both qualitative and quantitative advance plaque analysis by CCTA were performed by a core laboratory. In 129 cases, culprit lesions identified by invasive coronary angiography at the time of ACS were co-registered to baseline CCTA precursor lesions. The study population was then divided into subgroups according to sex and age (<65 vs. ≥ 65 years old) for analysis. Older patients had higher total plaque volume than younger patients. Within specific subtypes of plaque volume, however, only calcified plaque volume was higher in older patients (135.9 ± 163.7 vs. 63.8 ± 94.2 mm3, P < 0.0001, respectively). Although no sex-related differences were recorded for calcified plaque volume, females had lower fibrous and fibrofatty plaque volume than males (Fibrofatty volume 29.6 ± 44.1 vs. 75.3 ± 98.6 mm3, P = 0.0001, respectively). No sex-related differences in the prevalence of qualitative high-risk plaque features were found, even after separate analyses considering age were performed. CONCLUSION: Our data underline the importance of age- and sex-related differences in coronary atherosclerosis presentation, which should be considered during CCTA-based atherosclerosis quantification.