A Prospective Natural-History Study of Coronary Atherosclerosis

Study Questions:

What are the characteristics of atherosclerotic plaques that lead to recurrent acute coronary events?


A prospective study was conducted in 697 patients with acute coronary syndromes (ACS) who underwent three-vessel coronary angiography and gray-scale and radiofrequency intravascular ultrasonographic imaging after percutaneous coronary intervention (PCI). Subsequent major adverse cardiovascular events (CVEs; death from cardiac causes, cardiac arrest, myocardial infarction, or rehospitalization due to unstable or progressive angina) were adjudicated to be related to either originally treated (culprit) lesions or untreated (nonculprit) lesions. The median follow-up period was 3.4 years.


Median age was 58.1 years, 24% were women, 48% were smokers, mean low-density cholesterol was 94 mg/dl, and 17% were diabetic. Regarding PCIs, 95% were performed for an ST-elevation myocardial infarction (STEMI) or non-STEMI, 96% had stenting, and 27% had two-vessel PCI. The 3-year cumulative rate of CVEs was 20.4%. Events were adjudicated to be related to culprit lesions in 12.9% of patients and to nonculprit lesions in 11.6%. Most nonculprit lesions responsible for follow-up events were angiographically mild at baseline (mean [± standard deviation] diameter stenosis, 32.3 ± 20.6%). However, on multivariate analysis, nonculprit lesions associated with recurrent events were more likely than those not associated with recurrent events to be characterized by a plaque burden of 70% or greater (hazard ratio [HR], 5.03; 95% confidence interval [CI], 2.51-10.11; p < 0.001) or a minimal luminal area of 4.0 mm2 or less (HR, 3.21; 95% CI, 1.61-6.42; p = 0.001) or to be classified on the basis of radiofrequency intravascular ultrasonography as thin-cap fibroatheromas (HR, 3.35; 95% CI, 1.77-6.36; p < 0.001). The strongest patient-level predictor of nonculprit lesion–related CVE at follow-up was insulin-requiring diabetes, whereas a baseline plaque burden of at least 70%, a minimal luminal area of 4.0 mm2 or less, and the presence of thin-cap fibroatheromas were independent predictors of subsequent nonculprit lesion event. Events rarely originated from nonfibroatheromas, regardless of lesion severity.


In patients who presented with an acute coronary syndrome, coronary disease events occurring during follow-up were equally attributable to recurrence at the site of culprit lesions and to nonculprit lesions. Most initial nonculprit lesions were thin-cap fibroatheromas or were characterized by a large plaque burden and small luminal area or some combination.


This is an elegant and difficult study, whose in vivo results fit the known pathobiology of plaque and the Glagov phenomenon of remodeling. The results should not trigger the use of intravascular ultrasound to identify persons at risk with the consideration for PCI/stent. Only 18% of subjects with three predictive variables had recurrent clinical events, the great majority of which were angina. It is of interest that while 20% of subjects on contemporary medical therapy presented for repeat coronary angiography for clinical reasons, most were for unstable or progressive angina; the 3-year cumulative event rate for death from cardiac causes, cardiac arrest, or myocardial infarction was only 4.9% years.

Clinical Topics: Acute Coronary Syndromes, Arrhythmias and Clinical EP, Dyslipidemia, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Atherosclerotic Disease (CAD/PAD), Implantable Devices, SCD/Ventricular Arrhythmias, Lipid Metabolism, Nonstatins, Interventions and ACS, Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Echocardiography/Ultrasound, Nuclear Imaging

Keywords: Coronary Artery Disease, Acute Coronary Syndrome, Myocardial Infarction, Plaque, Atherosclerotic, Follow-Up Studies, Coronary Disease, Heart Arrest, Constriction, Pathologic, Percutaneous Coronary Intervention, Stents, Cholesterol, Coronary Angiography, Ultrasonography, Interventional

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