Atherosclerotic Precursors of Acute Coronary Syndromes

Study Questions:

What are the atherosclerotic features associated with precursors of acute coronary syndromes (ACS)?


The investigators performed a nested case-control study within a cohort of 25,251 patients undergoing coronary computed tomographic angiography (CCTA) with follow-up over 3.4 ± 2.1 years. ACS patients and nonevents with no prior coronary artery disease (CAD) were propensity matched 1:1 for risk factors and CCTA-evaluated obstructive (≥50%) CAD. Separate core labs performed blinded adjudication of ACS and culprit lesions and quantification of baseline CCTA for % diameter stenosis (%DS), % cross-sectional plaque burden (PB), plaque volumes (PVs) by composition (calcified, fibrous, fibro-fatty, and necrotic core), and presence of high-risk plaques (HRPs).


The investigators identified 234 ACS and control pairs (62 years, 63% male). Over 65% of ACS patients had nonobstructive CAD at baseline, and 52% had HRP. %DS, cross-sectional PB, fibro-fatty and necrotic core volume, and HRP increased the adjusted hazard ratio (HR) of ACS (1.010 per %DS, 95% confidence interval [CI], 1.005-1.015; 1.008 per % cross-sectional PB, 95% CI, 1.003-1.013; 1.002 per mm3 fibro-fatty plaque, 95% CI, 1.000-1.003; 1.593 per mm3 necrotic core, 95% CI, 1.219-2.082; all p < 0.05). Of the 129 culprit lesion precursors identified by CCTA, three-fourths exhibited <50% stenosis and 31.0% exhibited HRP.


The authors concluded that plaque evaluation, including HRP, PB, and plaque composition, identifies high-risk patients above and beyond stenosis severity and aggregate PB.


This multicenter case-control study reports that the majority of patients did not possess high-grade coronary stenosis before experiencing ACS. Coronary atherosclerotic precursors of ACS exhibited elevated fibro-fatty and necrotic core volumes, but not total or calcified volumes. Furthermore, HRPs and its features of low-attenuation plaque, positive remodeling, and spotty calcification, as well as cross-sectional PB, also identify lesions and patients who will experience ACS. These data suggest that quantitative measurement of plaque composition, as well as HRP evaluation and cross-sectional PB, needs to be investigated in future cohort studies for optimal risk stratification and possible prevention of ACS.

Clinical Topics: Acute Coronary Syndromes, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Atherosclerotic Disease (CAD/PAD), Interventions and ACS, Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Computed Tomography, Nuclear Imaging

Keywords: Acute Coronary Syndrome, Angiography, Atherosclerosis, Constriction, Pathologic, Coronary Artery Disease, Coronary Stenosis, Diagnostic Imaging, Myocardial Ischemia, Plaque, Atherosclerotic, Risk Factors, Secondary Prevention, Tomography, X-Ray Computed, Vascular Diseases

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